SARS-CoV-2 InfectionPhase 3NCT04955626

To Evaluate the Safety, Tolerability, Efficacy and Immunogenicity of BNT162b2 Boosting Strategies Against COVID-19 in Participants ≥12 Years of Age.

A Phase 3 study testing BNT162b2, BNT162b2 OMI and Combination BNT162b2 and BNT162b2 OMI in people with SARS-CoV-2 Infection and COVID-19, run by BioNTech SE at 154 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Substudy A: The study will evaluate the safety, tolerability, and efficacy of a booster dose of BNT162b2 when administered to participants having previously received 2 doses of BNT162b2 at least 6 months prior to randomization. Read more about this study

Who is it for?: Ages 12 years and olderHealthy volunteers can take part
Conditions the study is for: SARS-CoV-2 Infection, COVID-19
What is being tested?: BNT162b2, BNT162b2 OMI and Combination BNT162b2 and BNT162b2 OMI
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 16,372 participants
Where: 154 sitesin 5 countries
Study dates: 1 Jul 2021to 25 May 2023
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 years and older
All sexes
Healthy volunteers accepted
Child, Adult, Older adult

Who may be able to join

Male or female participants ≥16 years of age at Visit 1 (Day 1) who participated in C4591001.
Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
Capable of giving signed informed consent.
Participants who have received 2 prior doses of 30 µg BNT162b2 19-42 days apart, with the second dose being at least 175 days before Visit 1 (Day 1).
Male or female participants 12 to 30 years of age, inclusive, who have received 2 prior doses of 30 µg BNT162b2 19 to 60 days apart, with the second dose being at least at least 4 months (120 days) before Visit 1 (Day 1)

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Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
Capable of giving signed informed consent.
Male or female participants ≥12 years of age, inclusive, who have received 2 prior doses of 30 µg BNT162b2 19 to 60 days apart, with the second dose being at least 150 days before Visit 301 (Day 1)
Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
Capable of giving signed informed consent.
Male or female participants 18 to 55 years of age inclusive
Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
Cohort 2: Participants who provided a serum sample at Visit 3 in Study C4591001, with Visit 3 occurring within the protocol-specified window.
Capable of giving signed informed consent
Cohort 1: Participants who have received 2 prior doses of 30 µg BNT162b2, with the second dose being 90 to 240 days before Visit 401 (Day 1) or Cohort 2: Participants who have received 3 prior doses of 30 µg BNT162b2, with the third dose being 90 to 180 days before Visit 401 (Day 1).
Groups 1-6: Male or female participants >55 years of age
Groups 7-9: Male or female participants 18 to 55 years of age
Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
Capable of giving signed informed consent.
Participants who have received 3 prior doses of 30 µg BNT162b2, with the third dose being 5 to 12 months (150 to 360 days) before Visit 601 (Day 1).
Groups 7 to 9 (sentinel participants): Screening troponin levels must be within normal range prior to randomization.
Male or female participants ≥60 years of age
Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
Capable of giving signed informed consent.
Participants who have received 3 prior doses of 30 µg BNT162b2, with the third dose being ≥4 months before Visit 701 (Day 1).

Who cannot join

Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19.
Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
Women who are pregnant or breastfeeding.

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Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19, from 90 days before study intervention administration, or planned receipt throughout the study.
Prior receipt of any COVID-19 vaccine other than BNT162b2.
Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
Receipt of medications intended to prevent COVID-19.
Prior receipt of more than 2 doses of BNT162b2 30 µg.
Participation in other studies involving study intervention within 28 days prior to study entry, other than C4591001, and/or within 28 days of confirmed receipt of BNT162b2 within the study.
Substudy B
Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behaviour or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19.
Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
Women who are pregnant or breastfeeding.
Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19, from 90 days before study intervention administration, or planned receipt throughout the study.
Prior receipt of any COVID-19 vaccine other than BNT162b2.
Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
Receipt of medications intended to prevent COVID-19.
Prior receipt of more than 3 doses of BNT162b2 30 µg.
Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention, with the exception of non-Pfizer interventional studies for prevention of COVID-19, which are prohibited throughout study participation.
Substudy C
Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behaviour or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19.
Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
Women who are pregnant or breastfeeding.
Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19, from 90 days before study intervention administration, or planned receipt throughout the study.
Prior receipt of any COVID-19 vaccine other than BNT162b2.
Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
Receipt of medications intended to prevent COVID-19.
Prior receipt of more than 2 doses of BNT162b2 30 µg.
Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention, with the exception of non-Pfizer interventional studies for prevention of COVID-19, which are prohibited throughout study participation.
Substudy D
Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19.
Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
Women who are pregnant or breastfeeding.
Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19, from 90 days before study intervention administration, or planned receipt throughout the study.
Cohorts 1 and 2: prior receipt of any COVID-19 vaccine other than BNT162b2.
Cohort 3 only: prior receipt of any COVID-19 vaccine.
Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
Receipt of medications intended to prevent COVID 19.
Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention, with the exception of non-Pfizer interventional studies for prevention of COVID-19, which are prohibited throughout study participation.
Substudy E
Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19.
Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
Women who are pregnant or breastfeeding.
Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19, from 90 days before study intervention administration, or planned receipt throughout the study.
Prior receipt of any COVID-19 vaccine other than BNT162b2.
Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
Receipt of medications intended to prevent COVID-19.
Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention, with the exception of non-Pfizer interventional studies for prevention of COVID-19, which are prohibited throughout study participation.
Substudy F
Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19.
Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
Women who are pregnant or breastfeeding.
Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study.
Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19, from 90 days before study intervention administration, or planned receipt throughout the study.
Prior receipt of any COVID-19 vaccine other than BNT162b2.
Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
Receipt of medications intended to prevent COVID-19.
Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention, with the exception of non-Pfizer interventional studies for prevention of COVID-19, which are prohibited throughout study participation.

Trial locations and contacts

154 sites in 5 countries.

Country

City, postcode or hospital

154 sites in 5 countries

United States139 sites

Lehigh Valley Health Network/Network Office of Research and Innovation
Allentown, Pennsylvania, 18102
Anaheim Clinical Trials, LLC
Anaheim, California, 92801
Clinical Alliance for Research & Education - Infectious Diseases (CARE-ID)
Annandale, Virginia, 22003
North Alabama Research Center
Athens, Alabama, 35611
Lynn Institute of Denver
Aurora, Colorado, 80012
Benchmark Research
Austin, Texas, 78705
Innovo Research - Austin Regional Clinic
Austin, Texas, 78726
Tekton Research, Inc
Austin, Texas, 78745
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224
Kentucky Pediatric/ Adult Research
Bardstown, Kentucky, 40004
Meridian Clinical Research LLC
Binghamton, New York, 13901
Accel Research Sites - Birmingham Clinical Research Unit
Birmingham, Alabama, 35216
Boston Medical Center
Boston, Massachusetts, 02118
Bozeman Health Deaconess Hospital d/b/a Bozeman Health Clinical Research
Bozeman, Montana, 59715
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
Holston Medical Group
Bristol, Tennessee, 37620
Accellacare
Cary, North Carolina, 27518
Accellacare
Charlotte, North Carolina, 28211
Clinical Research Professionals
Chesterfield, Missouri, 63005
Johns Hopkins Center for American Indian Health
Chinle, Arizona, 86503
Meridian Clinical Research, LLC
Cincinnati, Ohio, 45219
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
Meridian Clinical Research
Cincinnati, Ohio, 45246
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
VA Northeast Ohio Healthcare System
Cleveland, Ohio, 44106
Velocity Clinical Research, Cleveland
Cleveland, Ohio, 44122
IACT Health
Columbus, Georgia, 31904
Centricity Research Columbus Ohio Multispecialty
Columbus, Ohio, 43213
Alliance for Multispecialty Research, LLC
Coral Gables, Florida, 33134
North Texas Infectious Diseases Consultants, P.A
Dallas, Texas, 75246
Dayton Clinical Research
Dayton, Ohio, 45406
Dayton Clinical Research
Dayton, Ohio, 45409
PriMED Clinical Research
Dayton, Ohio, 45419
Duke University - Main Hospital and Clinics
Durham, North Carolina, 27703
Velocity Clinical Research, Providence
East Greenwich, Rhode Island, 02818
Lillestol Research
Fargo, North Dakota, 58104
Michigan Center of Medical Research (MICHMER)
Farmington Hills, Michigan, 48334
Ventavia Research Group
Fort Worth, Texas, 76104
Benchmark Research
Fort Worth, Texas, 76135
Methodist Physicians Clinic/CCT Research
Fremont, Nebraska, 68025
Gallup Indian Medical Center
Gallup, New Mexico, 87301
Johns Hopkins Center for American Indian Health
Gallup, New Mexico, 87301
PharmQuest Life Sciences, LLC
Greensboro, North Carolina, 27408
Velocity Clinical Research, Covington
Gulfport, Mississippi, 39503
Indago Research & Health Center, Inc
Hialeah, Florida, 33012
Accellacare
Hickory, North Carolina, 28601
Research Centers of America ( Hollywood )
Hollywood, Florida, 33024
East-West Medical Research Institute
Honolulu, Hawaii, 96814
HG Pediatrics
Houston, Texas, 77008
Renu Garg, MD Pediatrics
Houston, Texas, 77008
Van Tran Family Practice
Houston, Texas, 77008
Ventavia Research Group, LLC
Houston, Texas, 77008
DM Clinical Research - Bellaire
Houston, Texas, 77081
Medical Affiliated Research Center
Huntsville, Alabama, 35801
University of Iowa
Iowa City, Iowa, 52242
Jacksonville Center for Clinical Research
Jacksonville, Florida, 32216
Clinical Neuroscience Solutions, Inc. dba CNS Healthcare
Jacksonville, Florida, 32256
SCR of Texas, LLC
Keller, Texas, 76248
Holston Medical Group
Kingsport, Tennessee, 37660
Alliance for Multispecialty Research - Weisgarber Medical Park
Knoxville, Tennessee, 37909
Wake Research - Clinical Research Center of Nevada, LLC
Las Vegas, Nevada, 89106
Main Street Physician's Care
Little River, South Carolina, 29566
Collaborative Neuroscience Research, LLC
Long Beach, California, 90806
Collaborative Neuroscience Research, LLC
Los Alamitos, California, 90720
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, 90027
Kaiser Permenente Medical Center Infectious Disease
Los Angeles, California, 90027
Velocity Clinical Research, Los Angeles
Los Angeles, California, 90057
Clinical Neuroscience Solutions Inc.
Memphis, Tennessee, 38119
Solaris Clinical Research
Meridian, Idaho, 83646
SMS Clinical Research
Mesquite, Texas, 75149
Acevedo Clinical Research Associates
Miami, Florida, 33142
Virginia Research Center
Midlothian, Virginia, 23114
Clinical Research Consulting
Milford, Connecticut, 06460
AMR Clinical
Mobile, Alabama, 36608
Clinical Research Associates Inc
Nashville, Tennessee, 37203
Yale University School of Medicine
New Haven, Connecticut, 06510
Yale-New Haven Hospital
New Haven, Connecticut, 06511
Yale Center for Clinical Investigation
New Haven, Connecticut, 06519
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121
NYU Langone Health
New York, New York, 10016
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
AMR Clinical
Newton, Kansas, 67114
Velocity Clinical Research, Norfolk
Norfolk, Nebraska, 68701
Lynn Institute of Norman
Norman, Oklahoma, 73072
Velocity Clinical Research, North Hollywood
North Hollywood, California, 91606
Kaiser Permanente Oakland
Oakland, California, 94611
Quality Clinical Research
Omaha, Nebraska, 68114
Velocity Clinical Research, Omaha
Omaha, Nebraska, 68134
Clinical Neuroscience Solutions, Inc.
Orlando, Florida, 32801
LinQ Research, LLC
Pearland, Texas, 77584
Hope Research Institute
Phoenix, Arizona, 85018
The Pain Center of Arizona
Phoenix, Arizona, 85018
HOPE Research Institute
Phoenix, Arizona, 85023
Kaiser Permanente Center for Health Research
Portland, Oregon, 97227
Accellacare
Raleigh, North Carolina, 27609
M3 Wake Research, Inc.
Raleigh, North Carolina, 27612
Paradigm Clinical Research Centers, Inc
Redding, California, 96001
Rochester Clinical Research, Inc.
Rochester, New York, 14609
University of Rochester Medical Center- Kari Steinmetz
Rochester, New York, 14642
University of Rochester Medical Center
Rochester, New York, 14642
UC Davis Medical Center
Sacramento, California, 95817
Accellacare - Salisbury
Salisbury, North Carolina, 28144
J. Lewis Research, Inc. / Foothill Family Clinic
Salt Lake City, Utah, 84109
J. Lewis Research, Inc. / Foothill Family Clinic South
Salt Lake City, Utah, 84121
Clinical Trials of Texas, Inc.
San Antonio, Texas, 78229
Clinical Trials of Texas, LLC
San Antonio, Texas, 78229
IMA Clinical Research San Antonio
San Antonio, Texas, 78229
California Research Foundation
San Diego, California, 92123
Kaiser Permanente Santa Clara
Santa Clara, California, 95051
Meridian Clinical Research
Savannah, Georgia, 31406
Benaroya Research Institute at Virginia Mason
Seattle, Washington, 98101
Johns Hopkins Center for American Indian Health
Shiprock, New Mexico, 87420
Northern Navajo Medical Center
Shiprock, New Mexico, 87420
Louisiana State University Health Sciences Shreveport
Shreveport, Louisiana, 71101
Velocity Clinical Research, Sioux City
Sioux City, Iowa, 51106
South Jersey Infectious Disease
Somers Point, New Jersey, 08244
Senders Pediatrics
South Euclid, Ohio, 44121
Sundance Clinical Research
St Louis, Missouri, 63141
Clinical Research Atlanta
Stockbridge, Georgia, 30281
SUNY Upstate Medical University
Syracuse, New York, 13215
Alliance for Multispecialty Research, LLC
Tempe, Arizona, 85281
DM Clinical Research - Kool Kids Pediatrics
Tomball, Texas, 77375
DM Clinical Research
Tomball, Texas, 77375
Trinity Clinical Research
Tullahoma, Tennessee, 37388
Bayview Research Group, LLC
Valley Village, California, 91607
Velocity Clinical Research, Vestal
Vestal, New York, 13850
Diablo Clinical Research, Inc.
Walnut Creek, California, 94598
IMA Clinical Research Warren
Warren Township, New Jersey, 07059
Research Building
Wenatchee, Washington, 98801
Wenatchee Valley Hospital
Wenatchee, Washington, 98801
Johns Hopkins Center for American Indian Health
Whiteriver, Arizona, 85941
Whiteriver Indian Hospital- Garrett Building
Whiteriver, Arizona, 85941
Whiteriver Indian Hospital
Whiteriver, Arizona, 85941
AMR Clinical
Wichita, Kansas, 67207
Accellacare (formerly PMG Research of Wilmington, LLC)
Wilmington, North Carolina, 28401
Accellacare
Wilmington, North Carolina, 28401
Accellacare
Winston-Salem, North Carolina, 27103
University of Massachusetts Chan Medical School
Worcester, Massachusetts, 01655

Other trials in United States

South Africa10 sites

Worthwhile Clinical Trials
Benoni, Gauteng, 1501
TREAD Research
Cape Town, Parow, 7500
Tiervlei Trial Centre
Cape Town, Western Cape, 7530
Synergy Biomed Research Institute
East London, Eastern Cape, 5201
Newtown Clinical Research
Johannesburg, Gauteng, 2113
Clinresco Centres
Kempton Park, Gauteng, 1619
Dr A Jacovides & Partners Inc.
Midrand, Gauteng, 1685
Botho Ke Bontle Health Services PTY LTD
Pretoria, Gauteng, 0184
Jongaie Research
Pretoria, 0183
Limpopo Clinical Research Initiative
Thabazimbi, Limpopo, 0380

Other trials in South Africa

Brazil2 sites

Obras Sociais Irma Dulce
Salvador, Estado de Bahia, 40.415-006
CEPIC - Centro Paulista de Investigação Clínica
São Paulo, 04266-010

Other trials in Brazil

Germany2 sites

Studienzentrum Dr. Keller
Frankfurt, 60389
IKF Pneumologie GmbH & Co. KG
Frankfurt, 60596

Other trials in Germany

Israel1 site

Sheba Medical Center
Ramat Gan, Central District, 5262100

Other trials in Israel

About this study

Official title: A PHASE 3 MASTER PROTOCOL TO EVALUATE ADDITIONAL DOSE(S) OF BNT162B2 IN HEALTHY INDIVIDUALS PREVIOUSLY VACCINATED WITH BNT162B2

The study is designed to describe vaccine efficacy of a booster dose of BNT162b2 over time against COVID-19

At a dose of 30µg (as studied in the Phase 2/3 study C4591001)
In healthy adults 16 years of age and older
The duration of the study for each participant will be up to approximately 12 months.
The study will be conducted in the United States, Brazil and South Africa

Substudy B: The study will assess the safety and tolerability of a single dose of BNT162b2 as compared to placebo control, through the potential analysis of serum troponin levels, in participants ≥12 and ≤30 years of age who have received 2 or 3 prior doses of BNT162b2 (30-µg doses) with their last dose at least 4 months (120 days) prior to randomization.

Blood samples will be collected for troponin testing
The duration of the study for each participant will be up to approximately 2 months.
The study will be conducted in the United States, Germany, Poland and South Africa

Substudy C: The study will assess the safety, tolerability, and immunogenicity of a booster (third) dose of BNT162b2 at doses of 10 µg or 30 µg in participants who have completed a 2-dose primary series of BNT162b2 (30 µg doses) at least 5 months (150 days) prior to randomization.

In healthy adults 12 years of age and older
The duration of the study for each participant will be up to approximately 12 months.
The study will be conducted in the United States, Germany and South Africa

Substudy D: The study will assess the safety, tolerability, and immunogenicity of a 2-dose primary series of BNT162b2 OMI, and as a booster (third, fourth or fifth) dose

Participants in Cohort 1 will have completed a 2-dose primary series of BNT162b2 (30-µg doses), with their last dose 90 to 240 days prior to enrolment
Participants in Cohort 2 will be enrolled from Study C4591001 and C4591031 Substudy A and will have completed a 2-dose primary series and received a single booster (third) dose of BNT162b2, with their last dose 90 to 180 days prior to randomization
Participants in Cohort 3 who are COVID-19 vaccine-naïve and have not experienced COVID-19 will be enrolled to receive 2 doses (primary series) of BNT162b2 OMI, 3 weeks apart, with a dose of BNT162b2 approximately 5 months (150 days) later. If participants do not consent to receive BNT162b2 as a third dose, they will not receive a third dose. No participants should receive BNT162b2 OMI as a third dose.
In healthy adults 18 to 55 years of age
The duration of the study for each participant will be up to approximately 12 months.
The study will be conducted in the United States and South Africa

Substudy E: This study will assess the safety, tolerability, and immunogenicity of high-dose BNT162b2 (60 µg), high-dose BNT162b2 OMI (60 µg), and a high-dose combination of BNT162b2 and BNT162b2 OMI at 60 µg (30 µg each), given as a single dose

In healthy adults 18 years of age and older who have received 3 prior doses of BNT162b2 (30 µg) with the most recent dose being 5 to 12 months (150 to 360 days) prior to randomization
The duration of the study for each participant will be approximately 6 months.
The study will be conducted in the United States

Substudy F: This study will assess the safety, tolerability, and immunogenicity of high-dose BNT162b2 (60 µg), high-dose BNT162b2 OMI (60 µg), and a high-dose combination of BNT162b2 and BNT162b2 OMI at 60 µg (30 µg each), given as a single dose.

In healthy adults 60 years of age and older who have received 3 prior doses of BNT162b2 (30 µg) with the most recent dose being ≥4 months prior to randomization
The duration of the study for each participant will be approximately 6 months.
The study will be conducted in Israel

Conditions: SARS-CoV-2 Infection, COVID-19
Being tested: BNT162b2, Placebo, BNT162b2 OMI, Combination BNT162b2 and BNT162b2 OMI, Combination (Bivalent) BNT162b2 and BNT162b2 OMI
Keywords: COVID-19, Coronavirus, Vaccine, SARS-CoV-2, RNA Vaccine
Medical subject headings: COVID-19, Coronavirus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BNT162b2Biological
Intramuscular Injection
PlaceboOther
Intramuscular Injection
BNT162b2 OMIBiological
Intramuscular Injection
Combination BNT162b2 and BNT162b2 OMIBiological
30-µg (15-µg each) or 60-µg (30-µg each)
Site prepared dosing suspension from 1 vial each of diluted BNT162b2 and BNT162b2 OMI
Intramuscular Injection
Combination (Bivalent) BNT162b2 and BNT162b2 OMIBiological
30-µg (15-µg each) or 60-µg (30-µg each)
Preformulated bivalent mixture (no dilution required) presented in a single vial
Intramuscular Injection

Study groups in NCT04955626
Study group	Role	What they receive
10 µg dose	Experimental	1 dose Receives: Biological: BNT162b2
Placebo	Placebo comparator	1 dose Receives: Other: Placebo
30 µg dose	Experimental	1 dose Receives: Biological: BNT162b2; Biological: BNT162b2 OMI; Biological: Combination BNT162b2 and BNT162b2 OMI; Biological: Combination (Bivalent) BNT162b2 and BNT162b2 OMI
60 µg dose	Experimental	1 dose Receives: Biological: BNT162b2; Biological: BNT162b2 OMI; Biological: Combination BNT162b2 and BNT162b2 OMI; Biological: Combination (Bivalent) BNT162b2 and BNT162b2 OMI

What is being measured

The primary outcome is the main question the study is designed to answer.

SSA: Occurrence of First COVID-19 Infection After Booster Dose Per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection at Interim Analysis: Evaluable Efficacy Population
Occurrences (number of cases) of first COVID-19 infection in participants after booster dose per 1000 person-year, without past SARS-CoV-2 infection at interim analysis were reported in this outcome measure.
Measured: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year [PY]) for BNT162b2 was 0.823 and for Placebo was 0.792
SSA: Occurrence of First COVID-19 Infection After Booster Dose Per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection at Interim Analysis: Evaluable Efficacy Population
Occurrences (number of cases) of first COVID-19 infection in participants after booster dose with and without past SARS-CoV-2 infection at interim analysis were reported in this outcome measure.
Measured: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 0.871 and for Placebo was 0.835
SSA: Occurrence of First COVID-19 Infection After Booster Dose Per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection at Final Analysis: Evaluable Efficacy Population
Occurrences (number of cases) of first COVID-19 infection in participants after booster dose without past SARS-CoV-2 infection at final analysis were reported in this outcome measure.
Measured: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 1.098 and for Placebo was 0.932
SSA: Occurrence of First COVID-19 Infection After Booster Dose Per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection at Final Analysis: Evaluable Efficacy Population
Occurrences (number of cases) of first COVID-19 infection in participants after booster dose with and without past SARS-CoV-2 infection at final analysis were reported in this outcome measure.
Measured: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 1.173 and for Placebo was 0.989
SSA: Percentage of Participants Reporting Adverse Events
An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Measured: From booster dose (Day 1) to 1 month after booster dose
SSA: Percentage of Participants Reporting Serious Adverse Events (SAE)
An SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect; or that was considered as an important medical event.
Measured: BNT162b2 30 mcg, Placebo then BNT162b2 30 mcg: From BNT162b2 dose to 6 months after BNT162b2 dose; Placebo: From placebo dose to unblinding for original placebo participants. Median blinded follow-up period for Placebo group=2.8 months
SSB: Percentage of Participants With Elevated Troponin I Level Pre-Dose; Vaccination 1
Percentage of participants with elevated troponin I levels before administration of Vaccination 1 were reported in this outcome measure.
Measured: Pre-dose on Day 1 (Vaccination 1)
SSB: Percentage of Participants With Elevated Troponin I Level Within 5 Days After Vaccination 1
Percentage of participants with elevated troponin I levels within 5 days after administration of Vaccination 1 were reported in this outcome measure.
Measured: Within 5 days after Vaccination 1
SSB: Percentage of Participants With Elevated Troponin I Level Pre-Vaccination 2 (1 Month After Vaccination 1)
Percentage of participants with elevated troponin I levels pre vaccination 2 were reported in this outcome measure.
Measured: Pre-Vaccination 2 (1 month after Vaccination 1)
SSB: Percentage of Participants With Elevated Troponin I Level Within 5 Days After Vaccination 2
Percentage of participants with elevated troponin I levels within 5 days after administration of Vaccination 2 were reported in this outcome measure.
Measured: Within 5 days after vaccination 2
SSB: Percentage of Participants With Elevated Troponin I Level 1 Month After Vaccination 2
Percentage of participants with elevated troponin I levels within 1 month after administration of Vaccination 2 were reported in this outcome measure.
Measured: 1 month after Vaccination 2
SSB: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 1
Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 centimeter (cm) and were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] or necrosis or exfoliative dermatitis [redness]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room [ER] visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after Vaccination 1 and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.
Measured: Day 1 up to Day 7 after Vaccination 1
SSB: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 2
Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 centimeter (cm) and were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] or necrosis or exfoliative dermatitis [redness]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room [ER] visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after Vaccination 2 and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.
Measured: Day 1 up to Day 7 after Vaccination 2
SSB: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 1
Systemic events were recorded in e-diary. Fever: oral temperature greater than or equal to (>=) 38.0 degree Celsius (deg C) and categorized as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit/hospitalization). Vomiting: mild: 1-2 times in 24 hours (h), moderate: >2 times in 24h, severe: required intravenous hydration and Grade 4: ER visit/hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit/hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.
Measured: Day 1 up to Day 7 after Vaccination 1
SSB: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 2
Systemic events were recorded in e-diary. Fever: oral temperature greater than or equal to (>=) 38.0 degree Celsius (deg C) and categorized as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit/hospitalization). Vomiting: mild: 1-2 times in 24 hours (h), moderate: >2 times in 24h, severe: required intravenous hydration and Grade 4: ER visit/hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit/hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.
Measured: Day 1 up to Day 7 after Vaccination 2
SSB: Percentage of Participants Reporting Adverse Events (AEs) 1 Month After Vaccination 1
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs within 1 month after Vaccination 1 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
Measured: Vaccination 1 up to 1 Month After Vaccination 1
SSB: Percentage of Participants Reporting Adverse Events (AEs) 1 Month After Vaccination 2
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs within 1 month after Vaccination 2 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
Measured: Vaccination 2 up to 1 month after Vaccination 2
SSB: Percentage of Participants Reporting Serious Adverse Events (SAEs) 1 Month After Vaccination 1
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
Measured: Vaccination 1 up to 1 month after Vaccination 1
SSB: Percentage of Participants Reporting Serious Adverse Events (SAEs) 1 Month After Vaccination 2
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
Measured: Vaccination 2 up to 1 month after Vaccination 2
SSC: Percentage of Participants With Local Reactions Within 7 Days After Booster Dose
Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 cm and were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] or necrosis or exfoliative dermatitis [redness]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room [ER] visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after the booster (third) dose and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.
Measured: Day 1 up to Day 7 after the booster dose
SSC: Percentage of Participants With Systemic Events Within 7 Days After Booster Dose
Systemic events were recorded in e-diary. Fever: oral temperature greater than or equal to (>=) 38.0 degree Celsius (deg C) and categorized as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit/hospitalization). Vomiting: mild: 1-2 times in 24 hours (h), moderate: >2 times in 24h, severe: required intravenous hydration and Grade 4: ER visit/hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24 h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit/hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.
Measured: Day 1 up to Day 7 after the booster dose
SSC: Percentage of Participants Reporting Adverse Events From Booster Dose Through 1 Month After Booster Dose
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs from booster (third) dose up to 1 month after booster (third) dose were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
Measured: From booster dose (Day 1) up to 1 month after booster dose
SSC: Percentage of Participants Reporting Serious Adverse Events From Booster Dose Through 6 Months After Booster Dose
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
Measured: From booster dose (Day 1) up to 6 months after booster dose
SSC: Geometric Mean Titers (GMT) of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Baseline
GMT of SARS-CoV-2 reference-strain-neutralizing titers at baseline (before the booster dose) was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
Measured: At baseline (pre-dose)
SSC: GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at 1 Month After the Booster Dose
GMT of SARS-CoV-2 reference-strain-neutralizing titers at 1 month after the booster dose was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
Measured: 1 month after the booster dose
SSC: Geometric Mean Fold-Rise (GMFR) of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Baseline to 1 Month After the Booster Dose
GMFR of SARS-CoV-2 reference-strain-neutralizing titers from baseline to 1 month after the booster dose received in this sub-study was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
Measured: From baseline to 1 month after the booster dose
SSC: Percentage of Participants With Seroresponse to Reference-Strain at 1 Month After the Booster Dose
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 1 month after the booster dose was reported in this outcome measure.
Measured: 1 month after the booster dose
SSD: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 1
Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu=0.5 centimeter (cm) and were graded as mild (> 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] or necrosis or exfoliative dermatitis [redness]). Pain at injection (inj) site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room [ER] visit/hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after Vaccination 1 and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.
Measured: Day 1 up to Day 7 after Vaccination 1
SSD: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 2
Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 centimeter (cm) and were graded as mild (> 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] or necrosis or exfoliative dermatitis [redness]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room [ER] visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after Vaccination 2 and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.
Measured: Day 1 up to Day 7 after Vaccination 2
SSD: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 3
Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 centimeter (cm) and were graded as mild (> 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] or necrosis or exfoliative dermatitis [redness]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room [ER] visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after Vaccination 3 and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.
Measured: Day 1 up to Day 7 after Vaccination 3
SSD: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 1
Systemic events were recorded in e-diary. Fever: oral temperature >= 38.0 deg C, categorized as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit/hospitalization). Vomiting: mild: 1-2 times in 24 h, moderate: >2 times in 24h, severe: required intravenous hydration and Grade 4: ER visit/hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit/hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.
Measured: Day 1 up to Day 7 after Vaccination 1
SSD: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 2
Systemic events were recorded in e-diary. Fever: oral temperature >= 38.0 deg C, categorized as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit/hospitalization). Vomiting: mild: 1-2 times in 24 h, moderate: >2 times in 24h, severe: required intravenous hydration and Grade 4: ER visit/hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit/hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.
Measured: Day 1 up to Day 7 after Vaccination 2
SSD: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 3
Systemic events were recorded in e-diary. Fever: oral temperature >= 38.0 deg C and categorized as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit/hospitalization). Vomiting: mild: 1-2 times in 24 hours (h), moderate: >2 times in 24h, severe: required intravenous hydration and Grade 4: ER visit/hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit/hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.
Measured: Day 1 up to Day 7 after Vaccination 3
SSD: Percentage of Participants Reporting Adverse Events (AEs) From First Study Vaccination (Day 1) Through 1 Month After Last Study Vaccination: Cohort 1
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs from first study vaccination (Day 1) up to 1 month after last study vaccination were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
Measured: From Day 1 up to 1 month after last study vaccination
SSD: Percentage of Participants Reporting Adverse Events (AEs) From First Study Vaccination (Day 1) Through 1 Month After Vaccination 1: Cohort 2
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs from first study vaccination (Day 1) up to 1 month after Vaccination 1 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
Measured: From first study vaccination (Day 1) up to 1 month after Vaccination 1
SSD: Percentage of Participants Reporting Adverse Events (AEs) From Second Study Vaccination Through 1 Month After Second Study Vaccination: Cohort 2
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs from Vaccination 2 up to 1 month after Vaccination 2 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
Measured: From Vaccination 2 up to 1 month after Vaccination 2
SSD: Percentage of Participants Reporting Adverse Events (AEs) From First Study Vaccination (Day 1) Through 1 Month After Second Study Vaccination: Cohort 3
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs from first study vaccination (Day 1) up to 1 month after Vaccination 2 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
Measured: From first study vaccination (Day 1) up to 1 month after Vaccination 2
SSD: Percentage of Participants Reporting Adverse Events (AEs) From Third Study Vaccination Through 1 Month After Third Study Vaccination: Cohort 3
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs from Vaccination 3 up to 1 month after Vaccination 3 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
Measured: From Vaccination 3 up to 1 month after Vaccination 3
SSD: Percentage of Participants Reporting Serious Adverse Events (SAEs) From First Study Vaccination (Day 1) Through 6 Months After Last Study Vaccination: Cohort 1 and Cohort 3
A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
Measured: From first study vaccination (Day 1) up to 6 months after last study vaccination
SSD: Percentage of Participants Reporting SAEs From First Study Vaccination (Day 1) Through 6 Months After Vaccination 1 (For Participants Who Received 1 Dose Only) and up to Vaccination 2 (For Participants Who Received 2 Doses): Cohort 2
A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
Measured: From vaccination 1 (Day 1) up to 6 months after vaccination 1 (participants received 1 dose only); From vaccination 1 up to before vaccination 2 (participants received 2 doses)
SSD: Percentage of Participants Reporting Serious Adverse Events (SAEs) From First Study Vaccination Through 6 Months After Vaccination 2: Cohort 2
A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
Measured: From first study vaccination (Day 1) up to 6 months after vaccination 2
SSD: GMR Based on Geometric Mean Titers of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers 1 Month After First Study Vaccination: Comparison Between Cohort 2 Group 3 and Group 4
GMR was calculated based on GMT levels of SSD: Cohort 2: Group 3 and SSD: Cohort 2: Group 4 and reported in statistical analysis section below. GMT of SARS-CoV-2 Omicron strain-neutralizing titers and reported in statistical analysis. GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers at 1 month after first study vaccination was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
Measured: 1 month after Vaccination 1
SSD: Percentage of Participants With Seroresponse to the SARS-CoV-2 Omicron BA.1 Strain at 1 Month After First Study Vaccination: Comparison Between Cohort 2 Group 3 and Group 4
Seroresponse: achieving >= 4-fold rise from baseline (before study vaccination). If baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse 1 month after first study vaccination was reported in this outcome measure.
Measured: 1 month after Vaccination 1
SSD: GMR Based on Geometric Mean Titers of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers 1 Month After First Study Vaccination: Comparison Between Cohort 1 Group 1 and Group 2b
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers at 1 month after first study vaccination was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
Measured: 1 month after Vaccination 1
SSD: GMR Based on Geometric Mean Titers of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers: Comparison Between 1 Month After Second Study Vaccination for Cohort 1 Group 2 and 1 Month After First Study Vaccination for Cohort 1 Group 2b
GMR was calculated based on GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers at 1 month after Vaccination 2 for Group 2 and 1 month after Vaccination 1 for Group 2b was reported. GMTs and corresponding 2-sided CIs were calculated by exponentiating mean logarithm of titers and corresponding CIs (based on Student's t distribution).
Measured: For Cohort 1 Group 2b:1 month after Vaccination 1; for Cohort 1 Group 2: 1 month after Vaccination 2
Percentage of Participants With Seroresponse to the SARS-CoV-2 Omicron BA.1 Strain at 1 Month After First Study Vaccination: Comparison Between Cohort 1 Group 1 and Group 2b
Seroresponse: achieving >= 4-fold rise from baseline (before study vaccination). If baseline measurement is below lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse 1 month after first study vaccination was reported in this outcome measure.
Measured: 1 month after Vaccination 1
SSD: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron BA.1 Strain at 1 Month After Vaccination 2: Comparison Between 1 Month After Vaccination 2 for Cohort 1 Group 2 and 1 Month After Vaccination 1 for Cohort 1 Group 2b
Seroresponse: achieving >= 4-fold rise from baseline (before study vaccination). If baseline measurement is below LLOQ, postvaccination measure of >= 4 × LLOQ is considered seroresponse. Exact 2-sided CI, based on Clopper and Pearson method was used. Percentage of participants achieving seroresponse 1 month after second study vaccination for Group 2 and 1 month after study vaccination for Group 2b was reported in this outcome measure.
Measured: For Cohort 1 Group 2b:1 month after Vaccination 1; for Cohort 1 Group 2: 1 month after Vaccination 2
SSD: GMR Based on Geometric Mean Titers of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers 1 Month After Second Study Vaccination: Cohort 3
GMR calculated based on GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMR comparison between GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers of participants of SSD Cohort 3: Group 5 to GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers of participants of study C4591001 (NCT04368728) Phase 3 BNT162b2 single arm 18-55 years of age, at 1 month after vaccination 2 was reported. GMTs and corresponding 2-sided CIs were calculated by exponentiating mean logarithm of titers and corresponding CIs (student's t distribution).
Measured: 1 month after Vaccination 2
SSD: Percentage of Participants With Seroresponse to the SARS-CoV-2 Omicron BA.1 Strain at 1 Month After Second Study Vaccination: Cohort 3
EIP:eligible participants received 2 doses of study drug as randomized with Dose2 received within 19-42 days after Dose1 (SSD Cohort 3:Group 5), had valid determinate immunogenicity result from blood sample collected within 28-42 days after 2nd study vaccination, had no other important protocol deviations as determined by clinician. Data of eligible participants from Study C4591001 Phase 3 BNT162b2 single arm 18-55 years was included for comparison.'N'=participants evaluable for outcome measure.
Measured: 1 month after Vaccination 2
SSE: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination
Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu=0.5 centimeter (cm) and were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm),severe (>10.0 cm) and Grade 4 (necrosis [swelling] or necrosis/exfoliative dermatitis [redness]).Pain at injection site was graded as mild (did not interfere with activity),moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room [ER] visit/hospitalization for severe pain). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions within 7 days after study vaccination and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.
Measured: Day 1 up to Day 7 after study vaccination
SSE: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination
Systemic events were recorded in e-diary. Fever: oral temperature greater than or equal to 38.0 deg C and categorized as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C \& >40.0 deg C. Fatigue, headache, chills, muscle pain and joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit or hospitalization). Vomiting: mild: 1-2 times in 24 h, moderate: > 2 times in 24h, severe: required intravenous hydration and Grade 4: ER or hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit or hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.
Measured: Day 1 up to Day 7 after study vaccination
SSE: Percentage of Participants Reporting Adverse Events (AEs) Within 1 Month After Study Vaccination
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs within 1 month after study vaccination were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
Measured: From study vaccination up to 1 Month after study vaccination
SSE: Percentage of Participants Reporting Serious Adverse Events (SAEs) Within 6 Month After Study Vaccination
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
Measured: From study vaccination up to 6 Months after study vaccination
SSE: Percentage of Participants With Elevated Troponin I Levels Before the Study Vaccination- 18 to 55 Years of Age
Percentage of participants with elevated troponin I levels before study vaccination were reported in this outcome measure.
Measured: Before study vaccination (pre-dose)
SSE: Percentage of Participants With Elevated Troponin I Levels 3 Days After Study Vaccination- 18 to 55 Years of Age
Percentage of participants with elevated troponin I levels before study vaccination were reported in this outcome measure.
Measured: 3 days after study vaccination
SSE: Geometric Mean Ratio (GMR) Based on Geometric Mean Titers of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers 1 Month After Study Vaccination
GMR calculated based on GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers at 1 month after the study vaccination was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
Measured: 1 month after study vaccination
SSE: Percentage of Participants With Seroresponse to the SARS-CoV-2 Omicron BA.1 Strain at 1 Month After Study Vaccination
Seroresponse was defined as achieving >= 4-fold rise from baseline (before study vaccination). If baseline measurement is below lower limit of quantification (LLOQ), postvaccination measure of >= 4 × LLOQ is considered seroresponse. Exact 2-sided CI, based on Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 1 month was reported in this outcome measure.
Measured: 1 month after study vaccination
SSF: Geometric Mean Titer (GMTs) of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers Before Vaccination
GMT of SARS-CoV-2 Omicron BA.1 strain neutralizing titers before vaccination was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
Measured: Before vaccination (pre-dose)
SSF: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination
Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 centimeter (cm) and were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (emergency room [ER] visit or hospitalization for severe pain). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (necrosis [swelling] or necrosis/exfoliative dermatitis [redness]). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after study vaccination and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.
Measured: Day 1 up to Day 7 after the study vaccination
SSF: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination
Systemic events were recorded in e-diary. Fever: oral temperature greater than or equal to 38.0 deg C and categorized as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C \& >40.0 deg C. Fatigue, headache, chills, muscle pain and joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit or hospitalization). Vomiting: mild: 1-2 times in 24 h, moderate: > 2 times in 24h, severe: required intravenous hydration and Grade 4: ER or hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit or hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.
Measured: Day 1 up to Day 7 after the study vaccination
SSF: Percentage of Participants Reporting Adverse Events (AEs) Within 1 Month After Study Vaccination
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs within 1 month after study vaccination were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
Measured: From study vaccination up to 1 Month after study vaccination
SSF: Percentage of Participants Reporting Serious Adverse Events (SAEs) Within 6 Months After Study Vaccination
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
Measured: From study vaccination up to 6 Months after study vaccination
SSF: GMTs of SARS-CoV-2 Reference-Strain-Neutralizing Titers Before Vaccination
GMT of SARS-CoV-2 reference-strain-neutralizing titers before vaccination was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
Measured: Before vaccination (pre-dose)
SSF: GMTs of SARS-CoV-2 Omicron BA.4/BA.5 Strain Neutralizing Titers Before Vaccination
GMT of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers before vaccination was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
Measured: Before vaccination (pre-dose)
SSF: Geometric Mean Ratio (GMR) Based on GMT of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers at Day 7
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.1 strain neutralizing titers at Day 7 were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
Measured: Day 7 (7 days after vaccination)
SSF: GMR Based on GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Day 7
GMR was calculated based on the GMT of SARS-CoV-2 Omicron reference strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 reference strain neutralizing titers at Day 7 were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
Measured: Day 7 (7 days after vaccination)
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.4/BA.5 Strain Neutralizing Titers at Day 7
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers at Day 7 were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
Measured: Day 7 (7 days after vaccination)
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers at Month 1
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.1 strain neutralizing titers at 1 month were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
Measured: Month 1 (1 month after vaccination)
SSF: GMR Based on GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Month 1
GMR was calculated based on the GMT of SARS-CoV-2 Omicron reference strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 reference strain neutralizing titers at 1 month were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
Measured: Month 1 (1 month after vaccination)
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 1
GMR was calculated based on the GMT of SARS-CoV-2 Omicron reference strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers at 1 month were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
Measured: Month 1 (1 month after vaccination)
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers at Month 3
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.1 strain neutralizing titers at 3 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
Measured: Month 3 (3 month after vaccination)
SSF: GMR Based on GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Month 3
GMR was calculated based on the GMT of SARS-CoV-2 Omicron reference strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 reference strain neutralizing titers at 3 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
Measured: Month 3 (3 month after vaccination)
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 3
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers at 3 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
Measured: Month 3 (3 month after vaccination)
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers at Month 6
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.1 strain neutralizing titers at 6 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
Measured: Month 6 (6 month after vaccination)
SSF: GMR Based on GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Month 6
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 reference strain neutralizing titers at 6 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
Measured: Month 6 (6 months after vaccination)
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 6
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers at 6 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
Measured: Month 6 (6 months after vaccination)
SSF: Geometric Mean Fold-Rise (GMFR) of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers From Before the Study Vaccination to 7 Days After Vaccination
GMFR of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers before vaccination to Day 7 was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
Measured: From before the study vaccination to Day 7 (7 days after vaccination)
SSF: GMFR of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Before the Study Vaccination to 7 Days After Vaccination
GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to Day 7 was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
Measured: From before the study vaccination to Day 7 (7 days after vaccination)
SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers From Before the Study Vaccination to 7 Days After Vaccination
GMFR of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers before vaccination to Day 7 was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
Measured: From before the study vaccination to Day 7 (7 days after vaccination)
SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers From Before the Study Vaccination to 1 Month After Vaccination
GMFR of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers before vaccination to 1 month was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
Measured: From before the study vaccination to 1 month after vaccination
SSF: GMFR of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Before the Study Vaccination to 1 Month After Vaccination
GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to 1 month was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
Measured: From before the study vaccination to 1 month after vaccination
SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers From Before the Study Vaccination to 1 Month After Vaccination
GMFR of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers before vaccination to 1 month was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
Measured: From before the study vaccination to 1 month after vaccination
SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination
GMFR of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers before vaccination to 3 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
Measured: From before the study vaccination to 3 months after vaccination
SSF: GMFR of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination
GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to 3 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
Measured: From before the study vaccination to 3 months after vaccination
SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination
GMFR of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers before vaccination to 3 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
Measured: From before the study vaccination to 3 months after vaccination
SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination
GMFR of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers before vaccination to 6 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
Measured: From before the study vaccination to 6 months after vaccination
SSF: GMFR of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination
GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to 6 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
Measured: From before the study vaccination to 6 months after vaccination
SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination
GMFR of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers before vaccination to 6 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
Measured: From before the study vaccination to 6 months after vaccination
SSF: Percentage of Participants With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Day 7
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse on Day 7 was reported in this outcome measure.
Measured: Day 7 (7 days after vaccination)
SSF: Percentage of Participants With Seroresponse to the Reference-Strain-Neutralizing Titers at Day 7
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse on Day 7 was reported in this outcome measure.
Measured: Day 7 (7 days after vaccination)
SSF: Percentage of Participants With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Day 7
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse on Day 7 was reported in this outcome measure.
Measured: Day 7 (7 days after vaccination)
SSF: Percentage of Participants With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 1
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 1 month was reported in this outcome measure.
Measured: Month 1 (1 month after vaccination)
SSF: Percentage of Participants With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 1
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 1 month was reported in this outcome measure.
Measured: Month 1 (1 month after vaccination)
SSF: Percentage of Participants With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 1
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 1 month was reported in this outcome measure.
Measured: Month 1 (1 month after vaccination)
SSF: Percentage of Participants With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 3
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 3 months was reported in this outcome measure.
Measured: Month 3 (3 months after vaccination)
SSF: Percentage of Participants With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 3
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 3 months was reported in this outcome measure.
Measured: Month 3 (3 months after vaccination)
SSF: Percentage of Participants With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 3
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 3 months was reported in this outcome measure.
Measured: Month 3 (3 months after vaccination)
SSF: Percentage of Participants With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 6
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 6 months was reported in this outcome measure.
Measured: Month 6 (6 months after vaccination)
SSF: Percentage of Participants With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 6
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 6 months was reported in this outcome measure.
Measured: Month 6 (6 months after vaccination)
SSF: Percentage of Participants With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 6
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 6 months was reported in this outcome measure.
Measured: Month 6 (6 months after vaccination)

Secondary outcomes (11)

SSA: Occurrence of First Severe COVID-19 Infection (FDA Definition) Per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection: Evaluable Efficacy Population
Occurrence (number of cases) of first severe COVID-19 infection based on FDA definition after booster dose without past SARS-CoV-2 infection is reported. FDA definition: confirmed COVID-19 and presence of at least 1 of the following: 1) clinical signs at rest indicative of severe systemic illness (respiratory rate greater than or equal to [>=]30 breaths per minute, heart rate >= 125 beats per minute, oxygen saturation less than or equal to [<=]93% on room air at sea level, or Horovitz quotient <300 mmHg); 2) respiratory failure (needing high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation); 3) evidence of shock (systolic blood pressure [BP] <90 mmHg, diastolic BP <60 mmHg, or requiring vasopressors); 4) significant acute renal, hepatic, or neurologic dysfunction; 5) admission to an intensive care unit; 6) death.
Measured: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 1.105 and for Placebo was 0.951
SSA: Occurrence of First Severe COVID-19 Infection (FDA Definition) Per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection: Evaluable Efficacy Population
Occurrence (number of cases) of first severe COVID-19 infection based on FDA definition after booster dose with and without past SARS-CoV-2 infection is reported. FDA definition: confirmed COVID-19 and presence of at least 1 of the following: 1) clinical signs at rest indicative of severe systemic illness (respiratory rate >= 30 breaths per minute, heart rate >= 125 beats per minute, oxygen saturation <= 93% on room air at sea level, or Horovitz quotient <300 mm Hg); 2) respiratory failure (defined as needing high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation); 3) evidence of shock (systolic BP <90 mm Hg, diastolic BP <60 mm Hg, or requiring vasopressors); 4) significant acute renal, hepatic, or neurologic dysfunction; 5) admission to an intensive care unit; 6) death.
Measured: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 1.182 and for Placebo was 1.011
SSA: Occurrence of First Severe COVID-19 Infection (CDC Definition) Per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection
Occurrence (number of cases) of first severe COVID-19 infection based on CDC definition after booster dose without past SARS-CoV-2 infection is reported. CDC definition: confirmed COVID-19 and presence of at least 1 of the following: 1) hospitalization; 2) admission to an intensive care unit; 3) intubation or mechanical ventilation; 4) death.
Measured: From 7 Days after booster vaccination
SSA: Occurrence of First Severe COVID-19 Infection (CDC Definition) Per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection
Occurrence (number of cases) of first severe COVID-19 infection based on CDC definition after booster dose with and without past SARS-CoV-2 infection is reported. CDC definition: confirmed COVID-19 AND presence of at least 1 of the following: 1) hospitalization; 2) admission to an intensive care unit; 3) intubation or mechanical ventilation; 4) death.
Measured: From 7 Days after booster vaccination
SSC: GMTs of SARS-CoV-2 Reference-Strain Neutralizing Titers at Baseline and 7 Days After the Booster Dose
GMT of SARS-CoV-2 reference-strain neutralizing titers at baseline and 7 days after the booster dose was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
Measured: At baseline and 7 days after the booster dose
SSC: GMTs of SARS-CoV-2 Omicron BA.1- Neutralizing Titers at Baseline and 7 Days After the Booster Dose
GMT of SARS-CoV-2 Omicron BA.1- neutralizing titers at baseline and 7 days after the booster dose was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
Measured: At baseline and 7 days after booster dose
SSC: GMFRs of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Baseline to 7 Days After the Booster Dose
GMFR of SARS-CoV-2 reference-strain-neutralizing titers from baseline (before the booster dose) to 7 days after the booster dose was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
Measured: From baseline (before booster dose) to 7 days after the booster dose
SSC: GMFRs of SARS-CoV-2 Omicron BA.1-Neutralizing Titers From Baseline to 7 Days After the Booster Dose
GMFR of SARS-CoV-2 Omicron BA.1-strain-neutralizing titers from baseline (before the booster dose) to 7 days after the booster dose was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
Measured: From baseline (before booster dose) to 7 days after the booster dose
SSC: Percentages of Participants With Seroresponse to Reference Strain at 7 Days After the Booster Dose
Seroresponse was defined as achieving >= 4-fold rise from before booster dose. If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse to reference strain at 7 days after the booster dose was reported in this outcome measure.
Measured: 7 days after the booster dose
SSC: Percentages of Participants With Seroresponse to Omicron BA.1 at 7 Days After the Booster Dose
Seroresponse was defined as achieving >= 4-fold rise from before booster dose. If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse to Omicron BA.1 strain at 7 days after the booster dose was reported in this outcome measure.
Measured: 7 days after the booster dose
SSE: GMR Based on Geometric Mean Titers of SARS-CoV-2 Reference Strain Neutralizing Titers at 1 Month After the Study Vaccination- >55 Years of Age
GMR based on GMT of SARS-CoV-2 reference strain neutralizing titers was calculated and reported in statistical analysis section. GMT of SARS-CoV-2 Reference strain-neutralizing titers at 1 month after the study vaccination was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
Measured: 1 month after study vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jul 202125 May 2023

First posted9 Jul 2021
Study start1 Jul 2021
Primary completion25 May 2023
Study completion25 May 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for SARS-CoV-2 InfectionStudies of the same condition, open and under way.
More trials run by BioNTech SEThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 16,372 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04955626
Sponsor's protocol ID: C4591031
Other IDs: 2021-005197-25
Status last verified: Oct 2025
First submitted: 9 Jun 2021
Last updated: 10 Nov 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Fitz-Patrick D, Sahgal O, Fouche LF, Mitha E, Malahleha M, Gayed J, Keep G, Zhang Y, Modjarrad K, Belanger T, Xu X, Cooper D, Mensa FJ, Sahin U, Tureci Ӧ, Swanson KA, Anderson AS, Gurtman A, Kitchin N. Immunogenicity, Tolerability, and Safety of BA.1-Adapted BNT162b2 Vaccine in 18- to 55-Year-Olds Previously Vaccinated with BNT162b2 or Who Were COVID-19 Vaccine-Naive. Infect Dis Ther. 2026 Jul 25. doi: 10.1007/s40121-026-01409-1. Online ahead of print.
PubMed 42501282
Winokur P, Diya O, Fitz-Patrick D, Dever M, Gayed J, Lockhart S, Xu X, Zhang Y, Bangad V, Wadsworth LT, Cannon K, Cardona JF, Usdan L, Ginis J, Mensa FJ, Zou J, Xie X, Lu C, Buitrago S, Scully IL, Cooper D, Koury K, Jansen KU, Tureci O, Sahin U, Swanson KA, Gruber WC, Kitchin N. Safety and Immunogenicity of a Fourth Dose of Omicron BA.1-Adapted BNT162b2 COVID-19 Vaccines in Adults 18-55 Years Old. Clin Infect Dis. 2026 May 20;82(5):e1083-e1092. doi: 10.1093/cid/ciag026.
PubMed 41560517
Muik A, Lui BG, Quandt J, Diao H, Fu Y, Bacher M, Gordon J, Toker A, Grosser J, Ozhelvaci O, Grikscheit K, Hoehl S, Kohmer N, Lustig Y, Regev-Yochay G, Ciesek S, Beguir K, Poran A, Vogler I, Tureci O, Sahin U. Progressive loss of conserved spike protein neutralizing antibody sites in Omicron sublineages is balanced by preserved T cell immunity. Cell Rep. 2023 Aug 29;42(8):112888. doi: 10.1016/j.celrep.2023.112888. Epub 2023 Jul 31.
PubMed 37527039
Winokur P, Gayed J, Fitz-Patrick D, Thomas SJ, Diya O, Lockhart S, Xu X, Zhang Y, Bangad V, Schwartz HI, Denham D, Cardona JF, Usdan L, Ginis J, Mensa FJ, Zou J, Xie X, Shi PY, Lu C, Buitrago S, Scully IL, Cooper D, Koury K, Jansen KU, Tureci O, Sahin U, Swanson KA, Gruber WC, Kitchin N; C4591031 Clinical Trial Group. Bivalent Omicron BA.1-Adapted BNT162b2 Booster in Adults Older than 55 Years. N Engl J Med. 2023 Jan 19;388(3):214-227. doi: 10.1056/NEJMoa2213082.
PubMed 36652353
Moreira ED Jr, Kitchin N, Xu X, Dychter SS, Lockhart S, Gurtman A, Perez JL, Zerbini C, Dever ME, Jennings TW, Brandon DM, Cannon KD, Koren MJ, Denham DS, Berhe M, Fitz-Patrick D, Hammitt LL, Klein NP, Nell H, Keep G, Wang X, Koury K, Swanson KA, Cooper D, Lu C, Tureci O, Lagkadinou E, Tresnan DB, Dormitzer PR, Sahin U, Gruber WC, Jansen KU; C4591031 Clinical Trial Group. Safety and Efficacy of a Third Dose of BNT162b2 Covid-19 Vaccine. N Engl J Med. 2022 May 19;386(20):1910-1921. doi: 10.1056/NEJMoa2200674. Epub 2022 Mar 23.
PubMed 35320659

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What is the study trying to find out?
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See locations

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SARS-CoV-2
Active, not recruitingObservational study
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COVID-19 SARS-CoV-2 Infection

All SARS-CoV-2 Infection trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A PHASE 3 MASTER PROTOCOL TO EVALUATE ADDITIONAL DOSE(S) OF BNT162B2 IN HEALTHY INDIVIDUALS PREVIOUSLY VACCINATED WITH BNT162B2
ClinicalTrials.gov ID: NCT04955626
Acronym / sponsor ID: C4591031
Conditions: SARS-CoV-2 Infection, COVID-19
Keywords: COVID-19, Coronavirus, Vaccine, SARS-CoV-2, RNA Vaccine
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 16,372 participants (actual)
Lead sponsor: BioNTech SEIndustry (pharma, biotech, devices)
Collaborators: Pfizer
Study start: 1 Jul 2021 (actual)
Primary completion: 25 May 2023 (actual)
Study completion: 25 May 2023 (actual)
First posted: 9 Jul 2021 (actual)
Results: Posted 10 Nov 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The study is designed to describe vaccine efficacy of a booster dose of BNT162b2 over time against COVID-19

At a dose of 30µg (as studied in the Phase 2/3 study C4591001)
In healthy adults 16 years of age and older
The duration of the study for each participant will be up to approximately 12 months.
The study will be conducted in the United States, Brazil and South Africa

Blood samples will be collected for troponin testing
The duration of the study for each participant will be up to approximately 2 months.
The study will be conducted in the United States, Germany, Poland and South Africa

In healthy adults 12 years of age and older
The duration of the study for each participant will be up to approximately 12 months.
The study will be conducted in the United States, Germany and South Africa

Substudy D: The study will assess the safety, tolerability, and immunogenicity of a 2-dose primary series of BNT162b2 OMI, and as a booster (third, fourth or fifth) dose

Participants in Cohort 1 will have completed a 2-dose primary series of BNT162b2 (30-µg doses), with their last dose 90 to 240 days prior to enrolment
Participants in Cohort 2 will be enrolled from Study C4591001 and C4591031 Substudy A and will have completed a 2-dose primary series and received a single booster (third) dose of BNT162b2, with their last dose 90 to 180 days prior to randomization
Participants in Cohort 3 who are COVID-19 vaccine-naïve and have not experienced COVID-19 will be enrolled to receive 2 doses (primary series) of BNT162b2 OMI, 3 weeks apart, with a dose of BNT162b2 approximately 5 months (150 days) later. If participants do not consent to receive BNT162b2 as a third dose, they will not receive a third dose. No participants should receive BNT162b2 OMI as a third dose.
In healthy adults 18 to 55 years of age
The duration of the study for each participant will be up to approximately 12 months.
The study will be conducted in the United States and South Africa

In healthy adults 18 years of age and older who have received 3 prior doses of BNT162b2 (30 µg) with the most recent dose being 5 to 12 months (150 to 360 days) prior to randomization
The duration of the study for each participant will be approximately 6 months.
The study will be conducted in the United States

In healthy adults 60 years of age and older who have received 3 prior doses of BNT162b2 (30 µg) with the most recent dose being ≥4 months prior to randomization
The duration of the study for each participant will be approximately 6 months.
The study will be conducted in Israel

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 4

Arm	Type	Receives
10 µg dose	Experimental	Biological: BNT162b21 dose
Placebo	Placebo comparator	Other: Placebo1 dose
30 µg dose	Experimental	Biological: BNT162b2, Biological: BNT162b2 OMI, Biological: Combination BNT162b2 and BNT162b2 OMI, Biological: Combination (Bivalent) BNT162b2 and BNT162b2 OMI1 dose
60 µg dose	Experimental	Biological: BNT162b2, Biological: BNT162b2 OMI, Biological: Combination BNT162b2 and BNT162b2 OMI, Biological: Combination (Bivalent) BNT162b2 and BNT162b2 OMI1 dose

Who may qualify

Ages: 12 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (31 listed)

Male or female participants ≥16 years of age at Visit 1 (Day 1) who participated in C4591001.
Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures.
Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
Capable of giving signed informed consent.
Participants who have received 2 prior doses of 30 µg BNT162b2 19-42 days apart, with the second dose being at least 175 days before Visit 1 (Day 1).

Key exclusion criteria (81 listed)

Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention.
Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19.
Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BNT162b2Intramuscular Injection	Biological	10 µg dose, 30 µg dose, 60 µg dose
PlaceboIntramuscular Injection	Other	Placebo
BNT162b2 OMIIntramuscular Injection	Biological	30 µg dose, 60 µg dose
Combination BNT162b2 and BNT162b2 OMI30-µg (15-µg each) or 60-µg (30-µg each) Site prepared dosing suspension from 1 vial each of diluted BNT162b2 and BNT162b2 OMI Intramuscular Injection	Biological	30 µg dose, 60 µg dose
Combination (Bivalent) BNT162b2 and BNT162b2 OMI30-µg (15-µg each) or 60-µg (30-µg each) Preformulated bivalent mixture (no dilution required) presented in a single vial Intramuscular Injection	Biological	30 µg dose, 60 µg dose

Primary outcome

SSA: Occurrence of First COVID-19 Infection After Booster Dose Per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection at Interim Analysis: Evaluable Efficacy Population
Time frame: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year [PY]) for BNT162b2 was 0.823 and for Placebo was 0.792
Occurrences (number of cases) of first COVID-19 infection in participants after booster dose per 1000 person-year, without past SARS-CoV-2 infection at interim analysis were reported in this outcome measure.
SSA: Occurrence of First COVID-19 Infection After Booster Dose Per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection at Interim Analysis: Evaluable Efficacy Population
Time frame: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 0.871 and for Placebo was 0.835
Occurrences (number of cases) of first COVID-19 infection in participants after booster dose with and without past SARS-CoV-2 infection at interim analysis were reported in this outcome measure.
SSA: Occurrence of First COVID-19 Infection After Booster Dose Per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection at Final Analysis: Evaluable Efficacy Population
Time frame: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 1.098 and for Placebo was 0.932
Occurrences (number of cases) of first COVID-19 infection in participants after booster dose without past SARS-CoV-2 infection at final analysis were reported in this outcome measure.
SSA: Occurrence of First COVID-19 Infection After Booster Dose Per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection at Final Analysis: Evaluable Efficacy Population
Time frame: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 1.173 and for Placebo was 0.989
Occurrences (number of cases) of first COVID-19 infection in participants after booster dose with and without past SARS-CoV-2 infection at final analysis were reported in this outcome measure.
SSA: Percentage of Participants Reporting Adverse Events
Time frame: From booster dose (Day 1) to 1 month after booster dose
An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention.
SSA: Percentage of Participants Reporting Serious Adverse Events (SAE)
Time frame: BNT162b2 30 mcg, Placebo then BNT162b2 30 mcg: From BNT162b2 dose to 6 months after BNT162b2 dose; Placebo: From placebo dose to unblinding for original placebo participants. Median blinded follow-up period for Placebo group=2.8 months
An SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect; or that was considered as an important medical event.
SSB: Percentage of Participants With Elevated Troponin I Level Pre-Dose; Vaccination 1
Time frame: Pre-dose on Day 1 (Vaccination 1)
Percentage of participants with elevated troponin I levels before administration of Vaccination 1 were reported in this outcome measure.
SSB: Percentage of Participants With Elevated Troponin I Level Within 5 Days After Vaccination 1
Time frame: Within 5 days after Vaccination 1
Percentage of participants with elevated troponin I levels within 5 days after administration of Vaccination 1 were reported in this outcome measure.
SSB: Percentage of Participants With Elevated Troponin I Level Pre-Vaccination 2 (1 Month After Vaccination 1)
Time frame: Pre-Vaccination 2 (1 month after Vaccination 1)
Percentage of participants with elevated troponin I levels pre vaccination 2 were reported in this outcome measure.
SSB: Percentage of Participants With Elevated Troponin I Level Within 5 Days After Vaccination 2
Time frame: Within 5 days after vaccination 2
Percentage of participants with elevated troponin I levels within 5 days after administration of Vaccination 2 were reported in this outcome measure.
SSB: Percentage of Participants With Elevated Troponin I Level 1 Month After Vaccination 2
Time frame: 1 month after Vaccination 2
Percentage of participants with elevated troponin I levels within 1 month after administration of Vaccination 2 were reported in this outcome measure.
SSB: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 1
Time frame: Day 1 up to Day 7 after Vaccination 1
Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 centimeter (cm) and were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] or necrosis or exfoliative dermatitis [redness]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room [ER] visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after Vaccination 1 and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.
SSB: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 2
Time frame: Day 1 up to Day 7 after Vaccination 2
Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 centimeter (cm) and were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] or necrosis or exfoliative dermatitis [redness]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room [ER] visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after Vaccination 2 and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.
SSB: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 1
Time frame: Day 1 up to Day 7 after Vaccination 1
Systemic events were recorded in e-diary. Fever: oral temperature greater than or equal to (>=) 38.0 degree Celsius (deg C) and categorized as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit/hospitalization). Vomiting: mild: 1-2 times in 24 hours (h), moderate: >2 times in 24h, severe: required intravenous hydration and Grade 4: ER visit/hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit/hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.
SSB: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 2
Time frame: Day 1 up to Day 7 after Vaccination 2
Systemic events were recorded in e-diary. Fever: oral temperature greater than or equal to (>=) 38.0 degree Celsius (deg C) and categorized as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit/hospitalization). Vomiting: mild: 1-2 times in 24 hours (h), moderate: >2 times in 24h, severe: required intravenous hydration and Grade 4: ER visit/hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit/hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.
SSB: Percentage of Participants Reporting Adverse Events (AEs) 1 Month After Vaccination 1
Time frame: Vaccination 1 up to 1 Month After Vaccination 1
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs within 1 month after Vaccination 1 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
SSB: Percentage of Participants Reporting Adverse Events (AEs) 1 Month After Vaccination 2
Time frame: Vaccination 2 up to 1 month after Vaccination 2
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs within 1 month after Vaccination 2 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
SSB: Percentage of Participants Reporting Serious Adverse Events (SAEs) 1 Month After Vaccination 1
Time frame: Vaccination 1 up to 1 month after Vaccination 1
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
SSB: Percentage of Participants Reporting Serious Adverse Events (SAEs) 1 Month After Vaccination 2
Time frame: Vaccination 2 up to 1 month after Vaccination 2
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
SSC: Percentage of Participants With Local Reactions Within 7 Days After Booster Dose
Time frame: Day 1 up to Day 7 after the booster dose
Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 cm and were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] or necrosis or exfoliative dermatitis [redness]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room [ER] visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after the booster (third) dose and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.
SSC: Percentage of Participants With Systemic Events Within 7 Days After Booster Dose
Time frame: Day 1 up to Day 7 after the booster dose
Systemic events were recorded in e-diary. Fever: oral temperature greater than or equal to (>=) 38.0 degree Celsius (deg C) and categorized as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit/hospitalization). Vomiting: mild: 1-2 times in 24 hours (h), moderate: >2 times in 24h, severe: required intravenous hydration and Grade 4: ER visit/hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24 h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit/hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.
SSC: Percentage of Participants Reporting Adverse Events From Booster Dose Through 1 Month After Booster Dose
Time frame: From booster dose (Day 1) up to 1 month after booster dose
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs from booster (third) dose up to 1 month after booster (third) dose were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
SSC: Percentage of Participants Reporting Serious Adverse Events From Booster Dose Through 6 Months After Booster Dose
Time frame: From booster dose (Day 1) up to 6 months after booster dose
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
SSC: Geometric Mean Titers (GMT) of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Baseline
Time frame: At baseline (pre-dose)
GMT of SARS-CoV-2 reference-strain-neutralizing titers at baseline (before the booster dose) was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
SSC: GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at 1 Month After the Booster Dose
Time frame: 1 month after the booster dose
GMT of SARS-CoV-2 reference-strain-neutralizing titers at 1 month after the booster dose was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
SSC: Geometric Mean Fold-Rise (GMFR) of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Baseline to 1 Month After the Booster Dose
Time frame: From baseline to 1 month after the booster dose
GMFR of SARS-CoV-2 reference-strain-neutralizing titers from baseline to 1 month after the booster dose received in this sub-study was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
SSC: Percentage of Participants With Seroresponse to Reference-Strain at 1 Month After the Booster Dose
Time frame: 1 month after the booster dose
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 1 month after the booster dose was reported in this outcome measure.
SSD: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 1
Time frame: Day 1 up to Day 7 after Vaccination 1
Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu=0.5 centimeter (cm) and were graded as mild (> 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] or necrosis or exfoliative dermatitis [redness]). Pain at injection (inj) site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room [ER] visit/hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after Vaccination 1 and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.
SSD: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 2
Time frame: Day 1 up to Day 7 after Vaccination 2
Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 centimeter (cm) and were graded as mild (> 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] or necrosis or exfoliative dermatitis [redness]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room [ER] visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after Vaccination 2 and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.
SSD: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 3
Time frame: Day 1 up to Day 7 after Vaccination 3
Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 centimeter (cm) and were graded as mild (> 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] or necrosis or exfoliative dermatitis [redness]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room [ER] visit or hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after Vaccination 3 and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.
SSD: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 1
Time frame: Day 1 up to Day 7 after Vaccination 1
Systemic events were recorded in e-diary. Fever: oral temperature >= 38.0 deg C, categorized as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit/hospitalization). Vomiting: mild: 1-2 times in 24 h, moderate: >2 times in 24h, severe: required intravenous hydration and Grade 4: ER visit/hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit/hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.
SSD: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 2
Time frame: Day 1 up to Day 7 after Vaccination 2
Systemic events were recorded in e-diary. Fever: oral temperature >= 38.0 deg C, categorized as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit/hospitalization). Vomiting: mild: 1-2 times in 24 h, moderate: >2 times in 24h, severe: required intravenous hydration and Grade 4: ER visit/hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit/hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.
SSD: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 3
Time frame: Day 1 up to Day 7 after Vaccination 3
Systemic events were recorded in e-diary. Fever: oral temperature >= 38.0 deg C and categorized as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit/hospitalization). Vomiting: mild: 1-2 times in 24 hours (h), moderate: >2 times in 24h, severe: required intravenous hydration and Grade 4: ER visit/hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit/hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.
SSD: Percentage of Participants Reporting Adverse Events (AEs) From First Study Vaccination (Day 1) Through 1 Month After Last Study Vaccination: Cohort 1
Time frame: From Day 1 up to 1 month after last study vaccination
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs from first study vaccination (Day 1) up to 1 month after last study vaccination were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
SSD: Percentage of Participants Reporting Adverse Events (AEs) From First Study Vaccination (Day 1) Through 1 Month After Vaccination 1: Cohort 2
Time frame: From first study vaccination (Day 1) up to 1 month after Vaccination 1
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs from first study vaccination (Day 1) up to 1 month after Vaccination 1 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
SSD: Percentage of Participants Reporting Adverse Events (AEs) From Second Study Vaccination Through 1 Month After Second Study Vaccination: Cohort 2
Time frame: From Vaccination 2 up to 1 month after Vaccination 2
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs from Vaccination 2 up to 1 month after Vaccination 2 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
SSD: Percentage of Participants Reporting Adverse Events (AEs) From First Study Vaccination (Day 1) Through 1 Month After Second Study Vaccination: Cohort 3
Time frame: From first study vaccination (Day 1) up to 1 month after Vaccination 2
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs from first study vaccination (Day 1) up to 1 month after Vaccination 2 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
SSD: Percentage of Participants Reporting Adverse Events (AEs) From Third Study Vaccination Through 1 Month After Third Study Vaccination: Cohort 3
Time frame: From Vaccination 3 up to 1 month after Vaccination 3
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs from Vaccination 3 up to 1 month after Vaccination 3 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
SSD: Percentage of Participants Reporting Serious Adverse Events (SAEs) From First Study Vaccination (Day 1) Through 6 Months After Last Study Vaccination: Cohort 1 and Cohort 3
Time frame: From first study vaccination (Day 1) up to 6 months after last study vaccination
A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
SSD: Percentage of Participants Reporting SAEs From First Study Vaccination (Day 1) Through 6 Months After Vaccination 1 (For Participants Who Received 1 Dose Only) and up to Vaccination 2 (For Participants Who Received 2 Doses): Cohort 2
Time frame: From vaccination 1 (Day 1) up to 6 months after vaccination 1 (participants received 1 dose only); From vaccination 1 up to before vaccination 2 (participants received 2 doses)
A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
SSD: Percentage of Participants Reporting Serious Adverse Events (SAEs) From First Study Vaccination Through 6 Months After Vaccination 2: Cohort 2
Time frame: From first study vaccination (Day 1) up to 6 months after vaccination 2
A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
SSD: GMR Based on Geometric Mean Titers of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers 1 Month After First Study Vaccination: Comparison Between Cohort 2 Group 3 and Group 4
Time frame: 1 month after Vaccination 1
GMR was calculated based on GMT levels of SSD: Cohort 2: Group 3 and SSD: Cohort 2: Group 4 and reported in statistical analysis section below. GMT of SARS-CoV-2 Omicron strain-neutralizing titers and reported in statistical analysis. GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers at 1 month after first study vaccination was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
SSD: Percentage of Participants With Seroresponse to the SARS-CoV-2 Omicron BA.1 Strain at 1 Month After First Study Vaccination: Comparison Between Cohort 2 Group 3 and Group 4
Time frame: 1 month after Vaccination 1
Seroresponse: achieving >= 4-fold rise from baseline (before study vaccination). If baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse 1 month after first study vaccination was reported in this outcome measure.
SSD: GMR Based on Geometric Mean Titers of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers 1 Month After First Study Vaccination: Comparison Between Cohort 1 Group 1 and Group 2b
Time frame: 1 month after Vaccination 1
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers at 1 month after first study vaccination was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
SSD: GMR Based on Geometric Mean Titers of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers: Comparison Between 1 Month After Second Study Vaccination for Cohort 1 Group 2 and 1 Month After First Study Vaccination for Cohort 1 Group 2b
Time frame: For Cohort 1 Group 2b:1 month after Vaccination 1; for Cohort 1 Group 2: 1 month after Vaccination 2
GMR was calculated based on GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers at 1 month after Vaccination 2 for Group 2 and 1 month after Vaccination 1 for Group 2b was reported. GMTs and corresponding 2-sided CIs were calculated by exponentiating mean logarithm of titers and corresponding CIs (based on Student's t distribution).
Percentage of Participants With Seroresponse to the SARS-CoV-2 Omicron BA.1 Strain at 1 Month After First Study Vaccination: Comparison Between Cohort 1 Group 1 and Group 2b
Time frame: 1 month after Vaccination 1
Seroresponse: achieving >= 4-fold rise from baseline (before study vaccination). If baseline measurement is below lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse 1 month after first study vaccination was reported in this outcome measure.
SSD: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron BA.1 Strain at 1 Month After Vaccination 2: Comparison Between 1 Month After Vaccination 2 for Cohort 1 Group 2 and 1 Month After Vaccination 1 for Cohort 1 Group 2b
Time frame: For Cohort 1 Group 2b:1 month after Vaccination 1; for Cohort 1 Group 2: 1 month after Vaccination 2
Seroresponse: achieving >= 4-fold rise from baseline (before study vaccination). If baseline measurement is below LLOQ, postvaccination measure of >= 4 × LLOQ is considered seroresponse. Exact 2-sided CI, based on Clopper and Pearson method was used. Percentage of participants achieving seroresponse 1 month after second study vaccination for Group 2 and 1 month after study vaccination for Group 2b was reported in this outcome measure.
SSD: GMR Based on Geometric Mean Titers of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers 1 Month After Second Study Vaccination: Cohort 3
Time frame: 1 month after Vaccination 2
GMR calculated based on GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMR comparison between GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers of participants of SSD Cohort 3: Group 5 to GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers of participants of study C4591001 (NCT04368728) Phase 3 BNT162b2 single arm 18-55 years of age, at 1 month after vaccination 2 was reported. GMTs and corresponding 2-sided CIs were calculated by exponentiating mean logarithm of titers and corresponding CIs (student's t distribution).
SSD: Percentage of Participants With Seroresponse to the SARS-CoV-2 Omicron BA.1 Strain at 1 Month After Second Study Vaccination: Cohort 3
Time frame: 1 month after Vaccination 2
EIP:eligible participants received 2 doses of study drug as randomized with Dose2 received within 19-42 days after Dose1 (SSD Cohort 3:Group 5), had valid determinate immunogenicity result from blood sample collected within 28-42 days after 2nd study vaccination, had no other important protocol deviations as determined by clinician. Data of eligible participants from Study C4591001 Phase 3 BNT162b2 single arm 18-55 years was included for comparison.'N'=participants evaluable for outcome measure.
SSE: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination
Time frame: Day 1 up to Day 7 after study vaccination
Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu=0.5 centimeter (cm) and were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm),severe (>10.0 cm) and Grade 4 (necrosis [swelling] or necrosis/exfoliative dermatitis [redness]).Pain at injection site was graded as mild (did not interfere with activity),moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room [ER] visit/hospitalization for severe pain). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions within 7 days after study vaccination and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.
SSE: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination
Time frame: Day 1 up to Day 7 after study vaccination
Systemic events were recorded in e-diary. Fever: oral temperature greater than or equal to 38.0 deg C and categorized as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C \& >40.0 deg C. Fatigue, headache, chills, muscle pain and joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit or hospitalization). Vomiting: mild: 1-2 times in 24 h, moderate: > 2 times in 24h, severe: required intravenous hydration and Grade 4: ER or hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit or hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.
SSE: Percentage of Participants Reporting Adverse Events (AEs) Within 1 Month After Study Vaccination
Time frame: From study vaccination up to 1 Month after study vaccination
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs within 1 month after study vaccination were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
SSE: Percentage of Participants Reporting Serious Adverse Events (SAEs) Within 6 Month After Study Vaccination
Time frame: From study vaccination up to 6 Months after study vaccination
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
SSE: Percentage of Participants With Elevated Troponin I Levels Before the Study Vaccination- 18 to 55 Years of Age
Time frame: Before study vaccination (pre-dose)
Percentage of participants with elevated troponin I levels before study vaccination were reported in this outcome measure.
SSE: Percentage of Participants With Elevated Troponin I Levels 3 Days After Study Vaccination- 18 to 55 Years of Age
Time frame: 3 days after study vaccination
Percentage of participants with elevated troponin I levels before study vaccination were reported in this outcome measure.
SSE: Geometric Mean Ratio (GMR) Based on Geometric Mean Titers of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers 1 Month After Study Vaccination
Time frame: 1 month after study vaccination
GMR calculated based on GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers at 1 month after the study vaccination was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
SSE: Percentage of Participants With Seroresponse to the SARS-CoV-2 Omicron BA.1 Strain at 1 Month After Study Vaccination
Time frame: 1 month after study vaccination
Seroresponse was defined as achieving >= 4-fold rise from baseline (before study vaccination). If baseline measurement is below lower limit of quantification (LLOQ), postvaccination measure of >= 4 × LLOQ is considered seroresponse. Exact 2-sided CI, based on Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 1 month was reported in this outcome measure.
SSF: Geometric Mean Titer (GMTs) of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers Before Vaccination
Time frame: Before vaccination (pre-dose)
GMT of SARS-CoV-2 Omicron BA.1 strain neutralizing titers before vaccination was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
SSF: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination
Time frame: Day 1 up to Day 7 after the study vaccination
Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 centimeter (cm) and were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (emergency room [ER] visit or hospitalization for severe pain). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (necrosis [swelling] or necrosis/exfoliative dermatitis [redness]). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after study vaccination and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.
SSF: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination
Time frame: Day 1 up to Day 7 after the study vaccination
Systemic events were recorded in e-diary. Fever: oral temperature greater than or equal to 38.0 deg C and categorized as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C \& >40.0 deg C. Fatigue, headache, chills, muscle pain and joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit or hospitalization). Vomiting: mild: 1-2 times in 24 h, moderate: > 2 times in 24h, severe: required intravenous hydration and Grade 4: ER or hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit or hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.
SSF: Percentage of Participants Reporting Adverse Events (AEs) Within 1 Month After Study Vaccination
Time frame: From study vaccination up to 1 Month after study vaccination
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants reporting AEs within 1 month after study vaccination were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
SSF: Percentage of Participants Reporting Serious Adverse Events (SAEs) Within 6 Months After Study Vaccination
Time frame: From study vaccination up to 6 Months after study vaccination
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
SSF: GMTs of SARS-CoV-2 Reference-Strain-Neutralizing Titers Before Vaccination
Time frame: Before vaccination (pre-dose)
GMT of SARS-CoV-2 reference-strain-neutralizing titers before vaccination was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
SSF: GMTs of SARS-CoV-2 Omicron BA.4/BA.5 Strain Neutralizing Titers Before Vaccination
Time frame: Before vaccination (pre-dose)
GMT of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers before vaccination was reported in this outcome measure. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution).
SSF: Geometric Mean Ratio (GMR) Based on GMT of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers at Day 7
Time frame: Day 7 (7 days after vaccination)
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.1 strain neutralizing titers at Day 7 were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
SSF: GMR Based on GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Day 7
Time frame: Day 7 (7 days after vaccination)
GMR was calculated based on the GMT of SARS-CoV-2 Omicron reference strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 reference strain neutralizing titers at Day 7 were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.4/BA.5 Strain Neutralizing Titers at Day 7
Time frame: Day 7 (7 days after vaccination)
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers at Day 7 were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers at Month 1
Time frame: Month 1 (1 month after vaccination)
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.1 strain neutralizing titers at 1 month were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
SSF: GMR Based on GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Month 1
Time frame: Month 1 (1 month after vaccination)
GMR was calculated based on the GMT of SARS-CoV-2 Omicron reference strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 reference strain neutralizing titers at 1 month were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 1
Time frame: Month 1 (1 month after vaccination)
GMR was calculated based on the GMT of SARS-CoV-2 Omicron reference strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers at 1 month were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers at Month 3
Time frame: Month 3 (3 month after vaccination)
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.1 strain neutralizing titers at 3 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
SSF: GMR Based on GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Month 3
Time frame: Month 3 (3 month after vaccination)
GMR was calculated based on the GMT of SARS-CoV-2 Omicron reference strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 reference strain neutralizing titers at 3 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 3
Time frame: Month 3 (3 month after vaccination)
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers at 3 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers at Month 6
Time frame: Month 6 (6 month after vaccination)
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.1 strain neutralizing titers at 6 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
SSF: GMR Based on GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Month 6
Time frame: Month 6 (6 months after vaccination)
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 reference strain neutralizing titers at 6 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 6
Time frame: Month 6 (6 months after vaccination)
GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers at 6 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.
SSF: Geometric Mean Fold-Rise (GMFR) of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers From Before the Study Vaccination to 7 Days After Vaccination
Time frame: From before the study vaccination to Day 7 (7 days after vaccination)
GMFR of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers before vaccination to Day 7 was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
SSF: GMFR of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Before the Study Vaccination to 7 Days After Vaccination
Time frame: From before the study vaccination to Day 7 (7 days after vaccination)
GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to Day 7 was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers From Before the Study Vaccination to 7 Days After Vaccination
Time frame: From before the study vaccination to Day 7 (7 days after vaccination)
GMFR of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers before vaccination to Day 7 was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers From Before the Study Vaccination to 1 Month After Vaccination
Time frame: From before the study vaccination to 1 month after vaccination
GMFR of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers before vaccination to 1 month was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
SSF: GMFR of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Before the Study Vaccination to 1 Month After Vaccination
Time frame: From before the study vaccination to 1 month after vaccination
GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to 1 month was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers From Before the Study Vaccination to 1 Month After Vaccination
Time frame: From before the study vaccination to 1 month after vaccination
GMFR of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers before vaccination to 1 month was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination
Time frame: From before the study vaccination to 3 months after vaccination
GMFR of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers before vaccination to 3 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
SSF: GMFR of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination
Time frame: From before the study vaccination to 3 months after vaccination
GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to 3 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination
Time frame: From before the study vaccination to 3 months after vaccination
GMFR of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers before vaccination to 3 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination
Time frame: From before the study vaccination to 6 months after vaccination
GMFR of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers before vaccination to 6 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
SSF: GMFR of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination
Time frame: From before the study vaccination to 6 months after vaccination
GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to 6 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination
Time frame: From before the study vaccination to 6 months after vaccination
GMFR of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers before vaccination to 6 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).
SSF: Percentage of Participants With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Day 7
Time frame: Day 7 (7 days after vaccination)
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse on Day 7 was reported in this outcome measure.
SSF: Percentage of Participants With Seroresponse to the Reference-Strain-Neutralizing Titers at Day 7
Time frame: Day 7 (7 days after vaccination)
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse on Day 7 was reported in this outcome measure.
SSF: Percentage of Participants With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Day 7
Time frame: Day 7 (7 days after vaccination)
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse on Day 7 was reported in this outcome measure.
SSF: Percentage of Participants With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 1
Time frame: Month 1 (1 month after vaccination)
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 1 month was reported in this outcome measure.
SSF: Percentage of Participants With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 1
Time frame: Month 1 (1 month after vaccination)
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 1 month was reported in this outcome measure.
SSF: Percentage of Participants With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 1
Time frame: Month 1 (1 month after vaccination)
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 1 month was reported in this outcome measure.
SSF: Percentage of Participants With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 3
Time frame: Month 3 (3 months after vaccination)
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 3 months was reported in this outcome measure.
SSF: Percentage of Participants With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 3
Time frame: Month 3 (3 months after vaccination)
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 3 months was reported in this outcome measure.
SSF: Percentage of Participants With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 3
Time frame: Month 3 (3 months after vaccination)
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 3 months was reported in this outcome measure.
SSF: Percentage of Participants With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 6
Time frame: Month 6 (6 months after vaccination)
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 6 months was reported in this outcome measure.
SSF: Percentage of Participants With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 6
Time frame: Month 6 (6 months after vaccination)
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 6 months was reported in this outcome measure.
SSF: Percentage of Participants With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 6
Time frame: Month 6 (6 months after vaccination)
Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 6 months was reported in this outcome measure.

11 secondary outcomes

SSA: Occurrence of First Severe COVID-19 Infection (FDA Definition) Per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection: Evaluable Efficacy Population
Time frame: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 1.105 and for Placebo was 0.951
SSA: Occurrence of First Severe COVID-19 Infection (FDA Definition) Per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection: Evaluable Efficacy Population
Time frame: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 1.182 and for Placebo was 1.011
SSA: Occurrence of First Severe COVID-19 Infection (CDC Definition) Per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection
Time frame: From 7 Days after booster vaccination
SSA: Occurrence of First Severe COVID-19 Infection (CDC Definition) Per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection
Time frame: From 7 Days after booster vaccination
SSC: GMTs of SARS-CoV-2 Reference-Strain Neutralizing Titers at Baseline and 7 Days After the Booster Dose
Time frame: At baseline and 7 days after the booster dose
SSC: GMTs of SARS-CoV-2 Omicron BA.1- Neutralizing Titers at Baseline and 7 Days After the Booster Dose
Time frame: At baseline and 7 days after booster dose
SSC: GMFRs of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Baseline to 7 Days After the Booster Dose
Time frame: From baseline (before booster dose) to 7 days after the booster dose
SSC: GMFRs of SARS-CoV-2 Omicron BA.1-Neutralizing Titers From Baseline to 7 Days After the Booster Dose
Time frame: From baseline (before booster dose) to 7 days after the booster dose
SSC: Percentages of Participants With Seroresponse to Reference Strain at 7 Days After the Booster Dose
Time frame: 7 days after the booster dose
SSC: Percentages of Participants With Seroresponse to Omicron BA.1 at 7 Days After the Booster Dose
Time frame: 7 days after the booster dose
SSE: GMR Based on Geometric Mean Titers of SARS-CoV-2 Reference Strain Neutralizing Titers at 1 Month After the Study Vaccination- >55 Years of Age
Time frame: 1 month after study vaccination

Results and safety

Results posted to the registry on 10 Nov 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
SSA: BNT162b2 30 mcg: Blinded and Open Label Period	5,080	421
SSA: Placebo: Blinded Period, Then BNT162b2 30 mcg Open-Label Period	5,041	22
SSB: BNT162b2 30 mcg Then Placebo	753	726
SSB: Placebo Then BNT162b2 30 mcg	732	693
SSC: BNT162b2 10 mcg	75	69
SSC: BNT162b2 30 mcg	65	58
SSD: Cohort 1: Group 1	216	197
SSD: Cohort 1: Group 2	197	183
SSD: Cohort 1: Group 2b	204	193
SSD: Cohort 2: Group 3	315	286
SSD: Cohort 2: Group 4	325	293
SSD: Cohort 3: Group 5	210	159
SSE: Sentinel Cohort (18-55 Years): BNT 30mcg + BNT OMI 30 mcg	30	28
SSE: Sentinel Cohort (18-55 Years): BNT 15 mcg +BNT OMI 15 mcg	30	30
SSE: Sentinel Cohort (18 to 55 Years): BNT162b2 OMI 60 mcg	30	27
SSE: Expanded Cohort (18-55 Years): BNT 30 mcg +BNT OMI 30 mcg	482	450
SSE: Expanded Cohort (18-55 Years): BNT 15 mcg +BNT OMI 15 mcg	159	151
SSE: Expanded Cohort (18 to 55 Years): BNT162b2 OMI 60 mcg	321	302
SSE: Sentinel Cohort (> 55 Years): BNT162b2 30 mcg	20	19
SSE: Sentinel Cohort (> 55 Years): BNT162b2 60 mcg	20	19
SSE: Sentinel Cohort (> 55 Years): BNT162b2 OMI 30 mcg	20	19
SSE: Sentinel Cohort (> 55 Years): BNT162b2 OMI 60 mcg	20	19
SSE: Sentinel Cohort (> 55 Years): BNT 15 mcg + BNT OMI 15 mcg	20	20
SSE: Sentinel Cohort (> 55 Years): BNT 30 mcg +BNT OMI 30 mcg	20	19
SSE: Expanded Cohort (> 55 Years): BNT162b2 30 mcg	305	292
SSE: Expanded Cohort (> 55 Years): BNT162b2 60 mcg	302	294
SSE: Expanded Cohort (> 55 Years): BNT162b2 OMI 30 mcg	307	291
SSE: Expanded Cohort (> 55 Years): BNT162b2 OMI 60 mcg	307	299
SSE: Expanded Cohort (> 55 Years): BNT 15 mcg + BNT OMI 15 mcg	308	294
SSE: Expanded Cohort (> 55 Years): BNT 30 mcg +BNT OMI 30 mcg	313	307
SSF: BNT162b2 30 mcg	21	21
SSF: BNT162b2 60 mcg	19	19
SSF: BNT162b2 OMI 30 mcg	21	21
SSF: BNT162b2 OMI 60 mcg	20	20
SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	20	20
SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg	21	21

Primary outcome: SSA: Occurrence of First COVID-19 Infection After Booster Dose Per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection at Interim Analysis: Evaluable Efficacy Population

Time frame: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year [PY]) for BNT162b2 was 0.823 and for Placebo was 0.792. Number. Unit: Number of first Covid-19 cases/1000 PY

Measure	SSA: BNT162b2 30 mcg: Blinded and Open Label Period n = 4659	SSA: Placebo: Blinded Period n = 4614
Value	7.290	155.303

SSA: BNT162b2 30 mcg: Blinded and Open Label Period vs SSA: Placebo: Blinded Period: Adjusted Surveillance Time: 95.3 (95% CI 89.5 to 98.3)

Population analysed: SSA evaluable efficacy population included all eligible randomized participants who received the booster vaccination as randomized and had no other important protocol deviations as determined by the clinician. Human Immunodeficiency Virus (HIV) positive participants were excluded from this analysis. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

Primary outcome: SSA: Occurrence of First COVID-19 Infection After Booster Dose Per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection at Interim Analysis: Evaluable Efficacy Population

Time frame: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 0.871 and for Placebo was 0.835. Number. Unit: Number of first Covid-19 cases/1000 PY

Measure	SSA: BNT162b2 30 mcg: Blinded and Open Label Period n = 4934	SSA: Placebo: Blinded Period n = 4863
Value	8.037	148.503

SSA: BNT162b2 30 mcg: Blinded and Open Label Period vs SSA: Placebo: Blinded Period: Adjusted Surveillance Time: 94.6 (95% CI 88.5 to 97.9)

Population analysed: SSA evaluable efficacy population included all eligible randomized participants who received the booster vaccination as randomized and had no other important protocol deviations as determined by the clinician. HIV positive participants were excluded from this analysis. Here, 'Number of Subjects Analyzed' signifies participants evaluable for this outcome measure.

Primary outcome: SSA: Occurrence of First COVID-19 Infection After Booster Dose Per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection at Final Analysis: Evaluable Efficacy Population

Time frame: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 1.098 and for Placebo was 0.932. Number. Unit: Number of first Covid-19 cases/1000 PY

Measure	SSA: BNT162b2 30 mcg: Blinded and Open Label Period n = 4639	SSA: Placebo: Blinded Period n = 4601
Value	57.377	158.798

SSA: BNT162b2 30 mcg: Blinded and Open Label Period vs SSA: Placebo: Blinded Period: Adjusted Surveillance Time: 63.9 (95% CI 51.1 to 73.5)

Population analysed: SSA evaluable efficacy population included all eligible randomized participants who received the booster vaccination as randomized and had no other important protocol deviations as determined by the clinician. HIV positive participants were excluded from this analysis. Here, 'Number of participants Analyzed' signifies participants evaluable for this outcome measure.

Primary outcome: SSA: Occurrence of First COVID-19 Infection After Booster Dose Per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection at Final Analysis: Evaluable Efficacy Population

Time frame: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 1.173 and for Placebo was 0.989. Number. Unit: Number of first Covid-19 cases/1000 PY

Measure	SSA: BNT162b2 30 mcg: Blinded and Open Label Period n = 4903	SSA: Placebo: Blinded Period n = 4846
Value	57.118	151.668

SSA: BNT162b2 30 mcg: Blinded and Open Label Period vs SSA: Placebo: Blinded Period: Adjusted Surveillance Time: 62.4 (95% CI 49.5 to 72.2)

Population analysed: SSA evaluable efficacy population included all eligible randomized participants who received the booster vaccination as randomized and had no other important protocol deviations as determined by the clinician. HIV positive participants were excluded from this analysis. Here, 'Number of participants Analyzed' signifies participants evaluable for this outcome measure.

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: Death/SAEs: 6 months after last dose (or 1 month after each dose for SSB, or 6 months after BNT162b2 for SSA original placebo). Non-SAEs: 1 month after each booster dose (or after Dose 2 for SSD naïve group, or after BNT162b2 for SSA original placebo). Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
SSA: BNT162b2 30 mcg- Blinded and Open Label Period	73 of 5,080 (1.4%)	1,201 of 5,080 (23.6%)	5 of 5,080
SSA: Placebo: Blinded Period	42 of 5,041 (0.8%)	202 of 5,041 (4%)	2 of 5,041
SSA: Original Placebo/BNT162b2 (30 mcg)- Open Label Period	45 of 4,429 (1%)	771 of 4,429 (17.4%)	5 of 4,429
SSB: BNT162b2	2 of 1,453 (0.1%)	1,180 of 1,453 (81.2%)	0 of 1,453
SSB: Placebo	2 of 1,463 (0.1%)	615 of 1,463 (42%)	0 of 1,463
SSF: BNT162b2 30 mcg	0 of 21 (0%)	17 of 21 (81%)	0 of 21
SSF: BNT162b2 60 mcg	1 of 19 (5.3%)	19 of 19 (100%)	0 of 19
SSF: BNT162b2 OMI 30 mcg	1 of 21 (4.8%)	20 of 21 (95.2%)	0 of 21
SSF: BNT162b2 OMI 60 mcg	0 of 20 (0%)	18 of 20 (90%)	0 of 20
SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	1 of 20 (5%)	18 of 20 (90%)	0 of 20
SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg	0 of 21 (0%)	20 of 21 (95.2%)	0 of 21
SSC: BNT162b2 10 mcg	0 of 75 (0%)	49 of 75 (65.3%)	0 of 75
SSC: BNT162b2 30 mcg	1 of 65 (1.5%)	57 of 65 (87.7%)	0 of 65
SSD: Cohort 1: Group 1	2 of 216 (0.9%)	124 of 216 (57.4%)	0 of 216
SSD: Cohort 1: Group 2a	3 of 197 (1.5%)	131 of 197 (66.5%)	2 of 197
SSD: Cohort 1: Group 2b	2 of 204 (1%)	109 of 204 (53.4%)	1 of 204
SSD: Cohort 2: Group 3a	5 of 315 (1.6%)

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42501282Fitz-Patrick D, Sahgal O, Fouche LF, Mitha E, Malahleha M, Gayed J, Keep G, Zhang Y, Modjarrad K, Belanger T, Xu X, Cooper D, Mensa FJ, Sahin U, Tureci Ӧ, Swanson KA, Anderson AS, Gurtman A, Kitchin N. Immunogenicity, Tolerability, and Safety of BA.1-Adapted BNT162b2 Vaccine in 18- to 55-Year-Olds Previously Vaccinated with BNT162b2 or Who Were COVID-19 Vaccine-Naive. Infect Dis Ther. 2026 Jul 25. doi: 10.1007/s40121-026-01409-1. Online ahead of print.
Derived from this study: PubMed 41560517Winokur P, Diya O, Fitz-Patrick D, Dever M, Gayed J, Lockhart S, Xu X, Zhang Y, Bangad V, Wadsworth LT, Cannon K, Cardona JF, Usdan L, Ginis J, Mensa FJ, Zou J, Xie X, Lu C, Buitrago S, Scully IL, Cooper D, Koury K, Jansen KU, Tureci O, Sahin U, Swanson KA, Gruber WC, Kitchin N. Safety and Immunogenicity of a Fourth Dose of Omicron BA.1-Adapted BNT162b2 COVID-19 Vaccines in Adults 18-55 Years Old. Clin Infect Dis. 2026 May 20;82(5):e1083-e1092. doi: 10.1093/cid/ciag026.
Derived from this study: PubMed 37527039Muik A, Lui BG, Quandt J, Diao H, Fu Y, Bacher M, Gordon J, Toker A, Grosser J, Ozhelvaci O, Grikscheit K, Hoehl S, Kohmer N, Lustig Y, Regev-Yochay G, Ciesek S, Beguir K, Poran A, Vogler I, Tureci O, Sahin U. Progressive loss of conserved spike protein neutralizing antibody sites in Omicron sublineages is balanced by preserved T cell immunity. Cell Rep. 2023 Aug 29;42(8):112888. doi: 10.1016/j.celrep.2023.112888. Epub 2023 Jul 31.
Derived from this study: PubMed 36652353Winokur P, Gayed J, Fitz-Patrick D, Thomas SJ, Diya O, Lockhart S, Xu X, Zhang Y, Bangad V, Schwartz HI, Denham D, Cardona JF, Usdan L, Ginis J, Mensa FJ, Zou J, Xie X, Shi PY, Lu C, Buitrago S, Scully IL, Cooper D, Koury K, Jansen KU, Tureci O, Sahin U, Swanson KA, Gruber WC, Kitchin N; C4591031 Clinical Trial Group. Bivalent Omicron BA.1-Adapted BNT162b2 Booster in Adults Older than 55 Years. N Engl J Med. 2023 Jan 19;388(3):214-227. doi: 10.1056/NEJMoa2213082.
Derived from this study: PubMed 35320659Moreira ED Jr, Kitchin N, Xu X, Dychter SS, Lockhart S, Gurtman A, Perez JL, Zerbini C, Dever ME, Jennings TW, Brandon DM, Cannon KD, Koren MJ, Denham DS, Berhe M, Fitz-Patrick D, Hammitt LL, Klein NP, Nell H, Keep G, Wang X, Koury K, Swanson KA, Cooper D, Lu C, Tureci O, Lagkadinou E, Tresnan DB, Dormitzer PR, Sahin U, Gruber WC, Jansen KU; C4591031 Clinical Trial Group. Safety and Efficacy of a Third Dose of BNT162b2 Covid-19 Vaccine. N Engl J Med. 2022 May 19;386(20):1910-1921. doi: 10.1056/NEJMoa2200674. Epub 2022 Mar 23.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pfizer CT.gov Call Center study director

Pfizer

154 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing BNT162b2, BNT162b2 OMI and Combination BNT162b2 and BNT162b2 OMI in people with SARS-CoV-2 Infection and COVID-19, run by BioNTech SE at 154 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 81 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 154 sites in United States, South Africa, Brazil, Germany, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

SSA: Occurrence of First COVID-19 Infection After Booster Dose Per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection at Interim Analysis: Evaluable Efficacy Population (time frame: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year [PY]) for BNT162b2 was 0.823 and for Placebo was 0.792). The study lists 100 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04955626, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2025; AzTrials last refreshed its copy on 8 Nov 2026.