SARS-CoV-2 InfectionPhase 2NCT05004181
Safety and Immunogenicity of RNA-based Vaccines Against SARS-CoV-2 Variants in Healthy Participants
A Phase 2 study testing BNT162b2, Multivalent BNT162b2 (B.1.1.7 + B.1.617.2) and Monovalent BNT162b2 (B.1.1.7) in people with SARS-CoV-2 Infection and COVID-19, run by BioNTech SE at 35 sites in 4 countries.
Trial summary
This trial consisted of three parts, Part A, Part B, and Part C, and evaluated the safety and immunogenicity of a third (booster) injection of the multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), and the safety and immunogenicity of a third booster injection of the monovalent vaccine BNT162b2 (B.1.617.2) or… Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- SARS-CoV-2 Infection, COVID-19, SARS-CoV-2 Acute Respiratory Disease
- What is being tested?
- BNT162b2, Multivalent BNT162b2 (B.1.1.7 + B.1.617.2) and Monovalent BNT162b2 (B.1.1.7)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,380 participants
- Where
- 35 sitesin 4 countries
- Study dates
- 25 Aug 2021to 4 Oct 2023
- Phase
- Phase 2
- 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 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Had given informed consent by signing the informed consent form (ICF) before initiation of any trial-specific procedures.
- Volunteers who at the time of consent were:
- Part A: 18 to 55 years old.
- Part B and Part C: 18 to 85 years old (~60% should be 18 to 55 years old and ~40% 56 to 85 years old).
- For Cohorts 1 to 5: In Part A, who had received BNT162b2 vaccine (30 µg, two-dose regimen) in either a clinical trial or as part of the governmental vaccination programs at least 6 months before Visit 0. Participants who were currently enrolled in the Phase III BNT162-02 / C4591001 (NCT04368728) trial, had already been unblinded, and had previously received two doses of BNT162b2 at least 6 months earlier could be included (for Cohorts 1 and 4 in Part B, prior enrollment and dosing in the C4591001 trial was mandatory). At enrollment into Part B of this trial, their participation in the C4591001 trial was terminated. Participants should have not had experienced COVID-19 based on medical history.
- For Cohort 6: Were COVID-19 vaccine-naïve and had not experienced COVID-19 based on their medical history.
Show all 19Show fewer
- Were willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other trial procedures.
- Were overall healthy at Visit 0 in the clinical judgment of the investigator based on the medical history, clinical assessment (including physical examination, vital signs, blood and urine clinical laboratory tests, 12-lead electrocardiogram (ECG), and oral swab for Nucleic Acid Amplification-based Test (NAAT)-based Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing).
- Note: Healthy volunteers with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 12 weeks before Visit 0, could be included.
- Note: Volunteers who had hepatitis C (HCV) infection, but had completed curative treatment based on the medical history could be included. Volunteers who had or have hepatitis B (HBV) or human immunodeficiency virus (HIV) based on the medical history could not be included.
- Agreed not to enroll in another trial of an Investigational Medicinal Product (IMP), starting after Visit 0 and continuously until the last planned visit in this trial.
- Women of childbearing potential (WOCBP) had to test negative in a urine beta-human chorionic gonadotropin (β-HCG) test at Visits 0 and 1.
- WOCBP had to agree to practice a highly effective form of contraception starting at Visit 0 and continuously until 28 days after their last IMP administration in this trial.
- WOCBP had to confirm that they practiced an acceptable form of contraception for the 14 days prior to Visit 0.
- WOCBP had to agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction starting after Visit 0 and continuously until 28 days after their last IMP injection in this trial.
- Men who are sexually active with a WOCBP and had not had a vasectomy had to agree to use a highly effective form of contraception with their female partner of childbearing potential starting after Visit 0 and continuously until 28 days after their last IMP injection in this trial.
- Men had to be willing to refrain from sperm donation, starting after Visit 0 and continuously until 28 days after their last vaccination.
- For Part C, Cohorts 7, 8, and 9: Had received two or three documented doses of any authorized COVID-19 RNA-based vaccine (e.g., BNT162b2 [Comirnaty] or the Moderna vaccine [Spikevax]) prior to being diagnosed with SARS-CoV-2 infection from January 2022 onwards (and limited to a period when there was a high prevalence of SARS-CoV-2 Omicron infections).
- Note: The interval between the last COVID-19 RNA-based vaccine administered and randomization should have been >4 months. The latest prior diagnosed SARS-CoV-2 infection should have been at least 2 months before randomization. The latest SARS-CoV-2 infection should have been documented with a result from a NAAT (as a preferable option). In case no historic NAAT result was available proving prior SARS-CoV-2 infection, the local positive result of SARS-CoV-2 N-binding antibodies done at screening was sufficient.
Who cannot join
- Any existing condition which could have affected vaccine injection and/or assessment of local reactions assessment, e.g., tattoos, severe scars, etc.
- Any bleeding diathesis or condition associated with prolonged bleeding that could have, in the opinion of the investigator, contraindicated intramuscular injection.
- Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that, in the investigator's judgment, made the participant inappropriate for the trial.
- Any current febrile illness (body temperature ≥38.0°C/≥100.4°F) or other acute illness within 48 h prior to Day 1/IMP injection in this trial.
- Any current or history of cardiovascular diseases, e.g., myocarditis, pericarditis, myocardial infarction, congestive heart failure, cardiomyopathy or clinically significant arrhythmias, unless such disease was not considered relevant for participation in this trial in the investigator's judgment.
- History of COVID-19 and/or 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) evidence of prior infection with SARS CoV 2 at screening (Visit 0).
Show all 22Show fewer
- Note: not applicable for Part C.
- History of Guillain-Barré syndrome.
- Known or suspected immunodeficiency.
- History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the trial IMPs.
- History or known allergy, hypersensitivity, or intolerance to the trial IMP including any excipients of the IMPs in this trial.
- Had received any SARS CoV 2 vaccination other than BNT162b2 (30 µg BNT162b2 given as a course of two doses approximately 21 days apart).
- Note: not applicable for Part C.
- Had received a live or live attenuated vaccine within 28 days prior to Day 1/IMP injection.
- Had received any other vaccines within 14 days before or after any IMP injection, e.g., influenza, tetanus, pneumococcal, hepatitis A or B. When possible standard of care vaccinations should been planned with the trial IMP administrations in mind.
- Individuals who received treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids were administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent), e.g., for cancer or an autoimmune disease, or planned receipt throughout this trial. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids were permitted.
- Receipt of blood/plasma products or immunoglobulin, from 60 days before IMP administration or planned receipt throughout this trial.
- Participation in other trials involving IMP within 28 days or 5 half-lives (whichever was longer) prior to Visit 1 and/or during trial participation, besides participation in trials with BNT162b2.
- Were pregnant or breastfeeding or are planning pregnancy within 28 days after last IMP treatment.
- Were vulnerable individuals as per International Conference on Harmonisation (ICH) E6 definition, i.e., are individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.
- For Part C, Cohorts 7, 8, and 9: Vaccination with other non-RNA or unauthorized COVID-19 vaccines.
- For Part C, Cohorts 7, 8, and 9: Vaccination with any COVID-19 vaccine after SARS-CoV-2 infection from January 2022 onwards (and limited to a period when there was a high prevalence of SARS-CoV-2 Omicron infections).
Trial locations and contacts
35 sites in 4 countries.
35 sites in 4 countries
United States14 sites
Atlanta Center for Medical Research
Atlanta, Georgia, 30331
ARC Clinical Research
Austin, Texas, 78745
Aventiv Research Inc.
Columbus, Ohio, 43213
North Texas Infectious Diseases Consultants
Dallas, Texas, 75246
Medpharmics, LLC
Gulfport, Mississippi, 39503
Collaborative Neuroscience Network LLC
Long Beach, California, 90806
Clinical Research Consulting, Llc
Milford, Connecticut, 06460
Rochester Clinical Research
Rochester, New York, 14609
Clinical Trials of Texas Inc.
San Antonio, Texas, 78229
Diagnostics Research Group
San Antonio, Texas, 78229
California Research Foundation
San Diego, California, 92123
Meridian Clinical Research
Savannah, Georgia, 31406
Stamford Therapeutics Consortium
Stamford, Connecticut, 06905
Amici Clinical Research
Warren Township, New Jersey, 07059
South Africa12 sites
Worthwhile Clinical Trials
Benoni, 01501
JOSHA Research
Bloemfontein, Free State, 09301
Tiervlei Trial Centre
Cape Town, 07530
Midrand Medical Centre
Halfway House, 01685
Newtown Clinical Research
Johannesburg, 02113
Langeberg Medicross Medical Centre
Kraaifontein, Western Cape, 75070
Paarl Research Centre
Paarl, Western Cape, 07646
Global Clinical Trials
Pretoria, 00001
Botho ke Bontle Health Service
Pretoria, 00122
Synexus SA Stanza Clinical Research Centre
Pretoria, 00122
Jongaie Research, Medicross Pretoria West
Pretoria, 00183
Synexus Helderberg Clinical Trial Centre
Somerset West, Western Cape, 07130
Turkey (Türkiye)5 sites
Ankara University Faculty of Medicine, Avicenna Hospital
Ankara, 06100
Hacettepe University Hospital
Ankara, 06100
Bagcilar Medipol Mega University Hospital
Istanbul, 34214
Istanbul University Medical Faculty
Istanbul, 34390
Kocaeli Universitesi Tip Fakultesi
Kocaeli, 41380
Germany4 sites
CRS Clinical Research Services Berlin
Berlin, 13353
IKF Institut fuer klinische Forschung Frankfurt
Frankfurt am Main, 60596
CRS Clinical Research Services Mannheim GmbH
Mannheim, 68167
Studienzentrum Brinkum Dr. Lars Pohlmeier und Torsten Drescher
Stuhr, 28816
About this study
Official title: A Phase II Trial to Evaluate the Safety and Immunogenicity of SARS-CoV-2 Monovalent and Multivalent RNA-based Vaccines in Healthy Subjects
This trial consisted of three parts, Part A, Part B, and Part C, and evaluated the safety and immunogenicity of a third (booster) injection of the multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), and the safety and immunogenicity of a third booster injection of the monovalent vaccine BNT162b2 (B.1.617.2) or BNT162b2 (B.1.1.7), in participants who had received two doses of the parent vaccine BNT162b2 at 30 µg, at least 6 months after the second dose of BNT162b2. It also evaluated the safety and immunogenicity of a three-dose regimen of BNT162b2 (B.1.1.7 + B.1.617.2) in participants who had not received prior Coronavirus Disease 2019 (COVID-19) vaccination. In addition, the safety and immunogenicity of BNT162b2 (B.1.1.529.1) or BNT162b2 given as a third or fourth vaccine dose to RNA COVID-19 vaccine-experienced participants with history of SARS-CoV-2 Omicron variant infection was evaluated and contrasted with the natural immune response reached after infection with the SARS-CoV-2 Omicron variant in RNA COVID-19 vaccine-experienced participants.
Read the detailed description
Trial participants in Part A were assigned to one of 6 cohorts (Cohort 1-6). Trial participants in Part B were assigned to one of 3 cohorts (Cohort 1, 4, and 6). Trial participants in Part C were randomized in a 2:2:1 ratio into 3 cohorts (Cohort 7-9).
- Being tested
- BNT162b2, Multivalent BNT162b2 (B.1.1.7 + B.1.617.2), Monovalent BNT162b2 (B.1.1.7), Monovalent BNT162b2 (B.1.617.2), Monovalent BNT162b2 (B.1.1.529.1)
- Medical subject headings
- COVID-19, Severe Acute Respiratory Syndrome, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BNT162b2Biological
Intramuscular (IM)
Multivalent BNT162b2 (B.1.1.7 + B.1.617.2)Biological
Intramuscular (IM)
Monovalent BNT162b2 (B.1.1.7)Biological
Intramuscular (IM)
Monovalent BNT162b2 (B.1.617.2)Biological
Intramuscular (IM)
Monovalent BNT162b2 (B.1.1.529.1)Biological
Intramuscular (IM)
ObservationalOther
No vaccination within 3 months after Visit 1.
| Study group | Role | What they receive |
|---|---|---|
| Part A - Cohort 1: 18 to 55 years of age | Experimental | Participants received 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg. Receives: Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2) |
| Part A - Cohort 2: 18 to 55 years of age | Experimental | Participants received 2 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg. Receives: Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2) |
| Part A - Cohort 3: 18 to 55 years of age | Experimental | Participants received1 dose of BNT162b2 (B.1.1.7) of 30 µg. Receives: Biological: Monovalent BNT162b2 (B.1.1.7) |
| Part A - Cohort 4: 18 to 55 years of age | Experimental | Participants received 1 dose of BNT162b2 (B.1.617.2) of 30 µg. Receives: Biological: Monovalent BNT162b2 (B.1.617.2) |
| Part A - Cohort 5: 18 to 55 years of age | Experimental | Participants received 1 dose of BNT162b2 of 30 µg. Receives: Biological: BNT162b2 |
| Part A - Cohort 6: 18 to 55 years of age | Experimental | Participants received 3 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg. Receives: Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2) |
| Part B - Cohort 1: 18 to 85 years of age | Experimental | Participants received 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg. Receives: Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2) |
| Part B - Cohort 4: 18 to 85 years of age | Experimental | Participants received 1 dose of BNT162b2 (B.1.617.2) of 30 µg. Receives: Biological: Monovalent BNT162b2 (B.1.617.2) |
| Part B - Cohort 6: 18 to 85 years of age | Experimental | Participants received 3 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg. Receives: Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2) |
| Part C - Cohort 7: 18 to 85 years of age | Experimental | Participants received 1 dose of BNT162b2 (B.1.1.529.1) of 30 µg. Receives: Biological: Monovalent BNT162b2 (B.1.1.529.1) |
| Part C - Cohort 8: 18 to 85 years of age | Experimental | Participants received 1 dose of BNT162b2 of 30 µg. Receives: Biological: BNT162b2 |
| Part C - Cohort 9: 18 to 85 years of age | Other | Participants received no vaccination within 3 months after Visit 1. Receives: Other: Observational |
What is being measured
The primary outcome is the main question the study is designed to answer.
All Parts - Percentage of Participants Reporting Local Reactions at the Injection Site (Pain, Tenderness, Erythema/Redness, Induration/Swelling)
Local reactions of any grade are reported. Local reactions were graded using criteria based on the US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"; the guidance uses the Grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening). The reporting of systemic reactions was based on the participant's assessments collected in the electronic diary (e-diary) or mapped from the adverse event case report form from Day 1 to Day 7 after each IMP dose. For Erythema/redness and Induration/swelling, the reported size had to be at least 2.5 cm to be deemed as a local reaction. Local reactions with a size less than 2.5 cm are not included in the analysis. Subjects in Cohort 9 did not receive a vaccination and are not included in this analysis.
Measured: from Day 1 to Day 7 after each IMP dose
All Parts - Percentage of Participants Reporting Systemic Events (Fever, Fatigue, Headache, Chills, Vomiting, Nausea, Diarrhea, New or Worsened Muscle Pain, and New or Worsened Joint Pain)
Systemic reactions of any grade are reported. Systemic reactions were graded using criteria based on the guidance given in the US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"; the guidance uses the Grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening). The reporting of systemic reactions was based on the participant's assessments collected in the e-diary or mapped from the adverse event case report form from Day 1 to Day 7 after each IMP dose. For Fever, the reported oral temperature had to be ≥38.0°C to be deemed as a systemic event. Oral temperature less than 38.0°C are not included in the analysis. Subjects in Cohort 9 did not receive a vaccination and are not included in this analysis.
Measured: from Day 1 to Day 7 after each IMP dose
All Parts - Percentage of Participants Reporting Adverse Events (AEs)
An AE is defined as TEAE if the event onset date and time is after the first IMP dose (if the event was absent before the first administration of the IMP) or worsened after the first IMP dose (if the event was present before the first administration of the IMP). In the event of an incomplete onset date, the event is considered as treatment-emergent unless the partial onset date information or complete or partial end date confirms the onset date or the event end prior to the first dose of IMP. Percentages for dose 1, dose 2, dose 3 and overall summaries are based upon the number of participants who received the respective IMP dose.
Measured: Dose 1 up to 1 month after each dose (all parts)
All Parts - Percentage of Participants Reporting Serious Adverse Events (SAEs)
An SAE was any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/ incapacity; was a congenital anomaly/birth defect and/or was another important medical event. SAEs from dose 1 up to 6 months post last IMP dose are presented. MedDRA (version 26.1) coding dictionary applied. An SAE is defined as TESAE if the event onset date and time is after the first IMP dose (if the event was absent before the first administration of the IMP) or worsened after the first IMP dose (if the event was present before the first administration of the IMP).
In the event of an incomplete onset date, the event is considered as treatment-emergent unless the partial onset date information or complete or partial end date confirms the onset date or the event end prior to the first dose of IMP.
Measured: Dose 1 up to 6 months after the last dose
Part B - GMR of B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial
GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and vaccine group. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.1.7 and reference strain respectively at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which GMR was derived) were secondary endpoints and are presented in outcome measure 22.
GMR = Geometric mean ratio; NT = neutralizing titers
Measured: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial
GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.617.2 and reference strain respectively at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which GMR was derived) were secondary endpoints and are presented in outcome measure 22.
GMR = Geometric mean ratio; NT = neutralizing titers
Measured: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial
GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.617.2 and reference strain respectively at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which GMR was derived) were secondary endpoints and are presented in outcome measure 24.
Measured: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - Difference in Seroresponse (SR) to B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)
Seroresponse was defined as a ≥4-fold rise in neutralizing titer from baseline. For subjects with a baseline titer less than the lower limit of quantitation (<LLOQ), seroresponse was defined as a post-vaccination titer of ≥4× LLOQ. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in seroresponse data are presented below as per the primary endpoint defined in the protocol. Seroresponses for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 23.
Measured: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)
Seroresponse was defined as a ≥4-fold rise in neutralizing titer from baseline. For subjects with a baseline titer less than the lower limit of quantitation (<LLOQ), seroresponse was defined as a post-vaccination titer of ≥4× LLOQ. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in seroresponse data are presented below as per the primary endpoint defined in the protocol. Seroresponses for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 23.
Measured: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)
Seroresponse was defined as a ≥4-fold rise in neutralizing titer from baseline. For subjects with a baseline titer less than the lower limit of quantitation (<LLOQ), seroresponse was defined as a post-vaccination titer of ≥4× LLOQ. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in seroresponse data are presented below as per the primary endpoint defined in the protocol. Seroresponses for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 25.
Measured: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - GMR of B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial
Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that the non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore, data were not available to calculate the GMR. Available GMT data for the 17 Cohort B6 participants without evidence of infection were analyzed and are presented in Outcome Measure 28.
Measured: 1 month
Part B - GMR of B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial
Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that the non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore, data were not available to calculate the GMR. Available GMT data for the 17 Part B Cohort 6 participants without evidence of infection were analyzed and are presented in Outcome Measure 28.
Measured: 1 month
Part B - The Difference in SR to B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial
Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore, data were not available to calculate difference in SR. Available SR data for the 17 Part B Cohort 6 participants without evidence of infection were analyzed and presented in Outcome Measure 31.
Measured: 1 month
Part B - The Difference in SR to B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial
Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that the non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore data were not available to calculate difference in SR. Available SR data for the 17 Part B Cohort 6 participants without evidence of infection were analyzed and presented in Outcome Measure 31.
Measured: 1 month
Part B - GMR of Reference Strain NT After One Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in Participants With Evidence of Prior Infection to the Reference Strain NT After 2 Doses of BNT162b2 in Participants Without Evidence of Infection
GMR of reference strain NT 3 weeks (3W) after one dose (PD1) of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection to the reference strain NT 1 month after two doses of BNT162b2 in participants without evidence of infection (COVID-19 Vaccine-naïve Participants) from the Phase III trial C4591001 (NCT04368728). GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and corresponding CIs (based on the Student t distribution). Assay results below LLOQ were set to 0.5 × LLOQ. GMTs of NTs are presented in the descriptive data section of this outcome measure. GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of LS means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. GMR data are presented in the statistical analysis section.
Measured: 3 weeks post Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - The Difference in SRs to the Reference Strain NT in Subjects With Evidence of Prior Infection and to the Reference Strain NT in Participants Without Evidence of Infection (COVID-19 Vaccine-naïve Participants)
The difference in SRs to the reference strain NT 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection to the reference strain NT 1 month after two doses of BNT162b2 in participants without evidence of infection from the Phase III trial C4591001 (NCT04368728). SR was defined as achieving a ≥4-fold rise from baseline. If the baseline measurement was below the LLOQ, a post-vaccination assay result ≥4 × LLOQ was considered a SR. SR to the reference strain NTs are presented in the descriptive data section of this outcome measure. Adjusted difference in proportions was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. 2-Sided CI was based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in SR data are presented in the statistical analysis section.
Measured: 3 weeks post Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part C - GMR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 and 8.
GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age and number of prior doses. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.1.529.1 at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 32.
Measured: 1 month after 1 dose of BNT162b2 or BNT162b2 (B.1.1.529.1)
Part C - The Difference in SR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 & 8.
SR was defined as a ≥4-fold rise in neutralizing titer from baseline. For participants with a baseline titer less than the lower limit of quantitation (<LLOQ), SR was defined as a post-vaccination titer of ≥4× LLOQ. SR to the reference strain NTs are presented in the descriptive data section of this outcome measure. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI were based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in SR data are presented in the statistical analysis section.
Measured: 1 month after 1 dose of BNT162b2 or BNT162b2 (B.1.1.529.1)
Secondary outcomes (14)
Part A - Geometric Mean Titer (GMT) at Each Timepoint
For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and variant(s) of concern (VOC) specific NT.
GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ.
Cohorts 1, 3, 4 and 5 received only 1 dose of IMP. Cohort 2 received dose 2 on Day 56 and did not receive dose 3. Cohort 6 received dose 2 on Day 21 and received dose 3 approximately 6 months after dose 2.
Measured: Day 1 up to Day 421
Part A - Geometric Mean Fold Rises (GMFR) From Before Vaccination to Each Subsequent Time Point After Vaccination
For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and VOC specific NT.
GMFR is calculated as the mean of the difference of logarithmically transformed neutralization titers or antibody levels (later result minus earlier result) and exponentiating the mean. The associated 2-sided 95% CIs are obtained by constructing CIs using Student's t-distribution for the mean difference on the natural log scale and exponentiating the confidence limits. Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ.
Cohorts 1, 3, 4 and 5 received only 1 dose of IMP. Cohort 2 received dose 2 on Day 56 and did not receive dose 3. Cohort 6 received dose 2 on Day 21 and received dose 3 approximately 6 months after dose 2.
Measured: Day 1 to Day 421
Part A - Percentage of Participants Achieving SR in Terms of NT at Each Post Vaccination Time Point
For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and VOC specific NT.
SR is defined as a ≥4-fold rise in neutralizing titer from baseline (pre IMP dose 1). For subjects with a baseline titer less than the LLOQ, SR is defined as a post-vaccination titer of ≥4 × LLOQ. Pre IMP dose 2 is also 2 months post dose 1 for Cohort 2 and 3 weeks post dose 1 for Cohort 6.
Cohorts 1, 3, 4 and 5 received only 1 dose of IMP. Cohort 2 received dose 2 on Day 56 and did not receive dose 3. Cohort 6 received dose 2 on Day 21 and received dose 3 approximately 6 months after dose 2.
Measured: Day 1 to Day 421
Part B - GMT of VOCs and Reference Strains in Part B Cohort 1 and Control
GMTs of VOCs (B.1.1.7 and B.1.617.2) and reference strain 1 month after 1 dose of BNT162 (B.1.1.7+B.1.167.2) in participants from Part B Cohort 1 of the BNT162-17 trial (BNT162b2-experienced participants), and reference strain 1 month after 2 doses of BNT162b2 in selected participants from the Phase III C4591001 (NCT04368728) trial.
GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ.
Measured: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - SR of of VOCs and Reference Strains in Part B Cohort 1 and Control
Percentage of participants achieving SR at 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants (Cohort 1) and 1 month after 2 doses of BNT162b2 primary series (participants from C4591001 [NCT04368728]). SR is defined as a ≥4-fold rise in neutralizing titer from baseline (pre IMP dose 1). For participants with a baseline titer less than the LLOQ, SR is defined as a post-vaccination titer of ≥4 × LLOQ.
Measured: 1 month after Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - GMT of VOCs and Reference Strains in Part B Cohort 4 and Control
GMTs of VOCs (B.1.617.2) and reference strain 1 month after 1 dose of BNT162 (B.1.167.2) in participants from Part B Cohort 4 of the BNT162-17 trial (BNT162b2-experienced participants), and 1 month after 2 doses of BNT162b2 in selected participants from the Phase III C4591001 (NCT04368728) trial.
GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ.
Measured: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - SR of of VOCs and Reference Strains in Part B Cohort 4 and Control
Percentage of participants achieving SR at 1 month after 1 dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced subjects (Part B - Cohort 4) and 1 month after 2 doses of BNT162b2 primary series (participants from C4591001 [NCT04368728]). SR is defined as a ≥4-fold rise in neutralizing titer from baseline (pre IMP dose 1). For participants with a baseline titer less than the LLOQ, SR is defined as a post-vaccination titer of ≥4 × LLOQ.
Measured: 1 month after Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - GMT of VOCs and Reference Strain in Part B Cohort 6 1 Month After Dose 2 and 1 Month After Dose 3
GMTs of VOCs and reference strain NT 1 month after dose 2 and dose 3 of BNT162b2 (B.1.1.7 + B.1.617.2) (Part B - Cohort 6). GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ.
Measured: 1 month after Dose 2 and 1 month after Dose 3
Part B - Cohort 6 - Percentages With SRs to VOCs (B.1.1.7, B.1.617.2) and Reference Strain
Percentage of participants achieving SR to VOCs (B.1.1.7, B.1.617.2) and reference strain at 1 month after dose 2 and dose 3 of BNT162b2 (B.1.1.7 + B.1.617.2) (Part B - Cohort 6).
SR is defined as a ≥4-fold rise in neutralizing titer from baseline (pre IMP dose 1). For participants with a baseline titer less than the LLOQ, SR is defined as a post vaccination titer of ≥4 × LLOQ. Pre IMP dose 2 is also 3 weeks post dose 1 for Cohort 6.
Measured: 1 month after Dose 2 and 1 month after Dose 3
Part B - GMTs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection in Part B C6 (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection in Part B C1 (1 Booster Dose)
GMTs of VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 [Omicron BA.5]) 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection (Cohort 6), 1 month after two doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants without evidence of infection (Cohort 6), and 1 month after one booster dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants without evidence of infection (Cohort 1). GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5 × LLOQ; assay results above the ULOQ were set to ULOQ.
Measured: Day 1 up to 1 month after 1 booster dose in Part B Cohort 1 without evidence of infection, up to 1 month after 2 doses in Part B Cohort 6 without evidence of infection and up to 3 weeks after 1 dose in Part B Cohort 6 with evidence of prior infection
Part B - GMRs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)
GMR of VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 [Omicron BA.5]) 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection (Cohort 6) to the VOCs NTs 1 month after two doses of BNT162b2 (B.1.1.7 + B.1.617.2) in participants without evidence of infection (Cohort 6), and to the VOCs NTs 1 month after one booster dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants without evidence of infection (Cohort 1). GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of the LS means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. A separate model was fit for each comparison. Assay results below the LLOQ were set to 0.5 × LLOQ; assay results above the ULOQ were set to ULOQ.
Measured: Day 1 to Day 29
Part B - Difference in SRs to VOCs in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)
The difference in SRs to VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 [Omicron BA.5]) 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection (Cohort 6) to those 1 month after two doses of BNT162b2 (B.1.1.7 + B.1.617.2) in participants without evidence of infection (Cohort 6), and to those 1 month after one booster dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants without evidence of infection (Cohort 1). Adjusted difference in proportions estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. 2-Sided CI based on the Newcombe method stratified by sex and age group (18 to 55 years, 56 to 85 years) with minimum risk weights for the difference in proportions.
Measured: Day 1 to Day 29
Part B - SR of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)
SRs of VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 [Omicron BA.5]) 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection (Cohort 6) 1 month after two doses of BNT162b2 (B.1.1.7 + B.1.617.2) in participants without evidence of infection (Cohort 6), and 1 month after one booster dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants without evidence of infection (Cohort 1). Seroresponse was defined as achieving a ≥4-fold rise from baseline. If the baseline measurement was below the LLOQ, a postvaccination assay result ≥4 × LLOQ was considered a seroresponse.
Measured: 3 weeks after one dose in participants with evidence of prior infection (Cohort 6), 1 month after two doses in participants without evidence of infection (Cohort 6), and 1 month after one booster dose (Cohort 1)
Part C - GMT - B.1.1.529.1 in RNA Based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection
VOC NT in RNA-based COVID-19 vaccine-experienced participants with history of SARS-CoV-2 infection at baseline and 7 days, 1 month, and 3 months after the trial start for Cohorts 7, 8, and 9, and 6 and 12 months after the trial start for Cohorts 7 and 8.
GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ. Number of subjects with valid and determinate assay results for the specified variant at the given dose/sampling time point. No vaccination was given to Cohort 9 participants within 3 months after Visit 1. The term "post IMP" does not apply for Cohort 9 since no IMP was given, but blood was collected at the same timepoints post randomization.
Measured: Day 1 to Day 360
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2021
- Study start25 Aug 2021
- Primary completion16 Aug 2023
- Study completion4 Oct 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 (3)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 2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,380 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioNTech SE
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- BioNTech Responsible Person, Study director, BioNTech SE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05004181
- Sponsor's protocol ID
- BNT162-17
- Other IDs
- 2021-003458-22
- Status last verified
- Nov 2024
- First submitted
- 5 Aug 2021
- Last updated
- 22 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Muik A, Quandt J, Lui BG, Bacher M, Lutz S, Grunenthal M, Toker A, Grosser J, Ozhelvaci O, Blokhina O, Shpyro S, Vogler I, Salisch N, Tureci O, Sahin U. Immunity against conserved epitopes dominates after two consecutive exposures to SARS-CoV-2 Omicron BA.1. Cell Rep. 2024 Aug 27;43(8):114567. doi: 10.1016/j.celrep.2024.114567. Epub 2024 Aug 3.
PubMed 39097927Muik 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 37527039Muik A, Lui BG, Bacher M, Wallisch AK, Toker A, Couto CIC, Guler A, Mampilli V, Schmitt GJ, Mottl J, Ziegenhals T, Fesser S, Reinholz J, Wernig F, Schraut KG, Hefesha H, Cai H, Yang Q, Walzer KC, Grosser J, Strauss S, Finlayson A, Kruger K, Ozhelvaci O, Grikscheit K, Kohmer N, Ciesek S, Swanson KA, Vogel AB, Tureci O, Sahin U. Exposure to BA.4/5 S protein drives neutralization of Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5 in vaccine-experienced humans and mice. Sci Immunol. 2022 Dec 23;7(78):eade9888. doi: 10.1126/sciimmunol.ade9888. Epub 2022 Dec 23.
PubMed 36378074
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial to Evaluate the Safety and Immunogenicity of SARS-CoV-2 Monovalent and Multivalent RNA-based Vaccines in Healthy Subjects
- ClinicalTrials.gov ID
- NCT05004181
- Acronym / sponsor ID
- BNT162-17
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,380 participants (actual)
- Lead sponsor
- BioNTech SEIndustry (pharma, biotech, devices)
- Study start
- 25 Aug 2021 (actual)
- Primary completion
- 16 Aug 2023 (actual)
- Study completion
- 4 Oct 2023 (actual)
- First posted
- 13 Aug 2021 (actual)
- Results
- Posted 22 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial consisted of three parts, Part A, Part B, and Part C, and evaluated the safety and immunogenicity of a third (booster) injection of the multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), and the safety and immunogenicity of a third booster injection of the monovalent vaccine BNT162b2 (B.1.617.2) or BNT162b2 (B.1.1.7), in participants who had received two doses of the parent vaccine BNT162b2 at 30 µg, at least 6 months after the second dose of BNT162b2. It also evaluated the safety and immunogenicity of a three-dose regimen of BNT162b2 (B.1.1.7 + B.1.617.2) in participants who had not received prior Coronavirus Disease 2019 (COVID-19) vaccination. In addition, the safety and immunogenicity of BNT162b2 (B.1.1.529.1) or BNT162b2 given as a third or fourth vaccine dose to RNA COVID-19 vaccine-experienced participants with history of SARS-CoV-2 Omicron variant infection was evaluated and contrasted with the natural immune response reached after infection with the SARS-CoV-2 Omicron variant in RNA COVID-19 vaccine-experienced participants.
Detailed description
Trial participants in Part A were assigned to one of 6 cohorts (Cohort 1-6). Trial participants in Part B were assigned to one of 3 cohorts (Cohort 1, 4, and 6). Trial participants in Part C were randomized in a 2:2:1 ratio into 3 cohorts (Cohort 7-9).
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Part A - Cohort 1: 18 to 55 years of age | Experimental | Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2)Participants received 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg. |
| Part A - Cohort 2: 18 to 55 years of age | Experimental | Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2)Participants received 2 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg. |
| Part A - Cohort 3: 18 to 55 years of age | Experimental | Biological: Monovalent BNT162b2 (B.1.1.7)Participants received1 dose of BNT162b2 (B.1.1.7) of 30 µg. |
| Part A - Cohort 4: 18 to 55 years of age | Experimental | Biological: Monovalent BNT162b2 (B.1.617.2)Participants received 1 dose of BNT162b2 (B.1.617.2) of 30 µg. |
| Part A - Cohort 5: 18 to 55 years of age | Experimental | Biological: BNT162b2Participants received 1 dose of BNT162b2 of 30 µg. |
| Part A - Cohort 6: 18 to 55 years of age | Experimental | Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2)Participants received 3 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg. |
| Part B - Cohort 1: 18 to 85 years of age | Experimental | Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2)Participants received 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg. |
| Part B - Cohort 4: 18 to 85 years of age | Experimental | Biological: Monovalent BNT162b2 (B.1.617.2)Participants received 1 dose of BNT162b2 (B.1.617.2) of 30 µg. |
| Part B - Cohort 6: 18 to 85 years of age | Experimental | Biological: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2)Participants received 3 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg. |
| Part C - Cohort 7: 18 to 85 years of age | Experimental | Biological: Monovalent BNT162b2 (B.1.1.529.1)Participants received 1 dose of BNT162b2 (B.1.1.529.1) of 30 µg. |
| Part C - Cohort 8: 18 to 85 years of age | Experimental | Biological: BNT162b2Participants received 1 dose of BNT162b2 of 30 µg. |
| Part C - Cohort 9: 18 to 85 years of age | Other | Other: ObservationalParticipants received no vaccination within 3 months after Visit 1. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Had given informed consent by signing the informed consent form (ICF) before initiation of any trial-specific procedures.
- Volunteers who at the time of consent were:
- Part A: 18 to 55 years old.
- Part B and Part C: 18 to 85 years old (~60% should be 18 to 55 years old and ~40% 56 to 85 years old).
- For Cohorts 1 to 5: In Part A, who had received BNT162b2 vaccine (30 µg, two-dose regimen) in either a clinical trial or as part of the governmental vaccination programs at least 6 months before Visit 0. Participants who were currently enrolled in the Phase III BNT162-02 / C4591001 (NCT04368728) trial, had already been unblinded, and had previously received two doses of BNT162b2 at least 6 months earlier could be included (for Cohorts 1 and 4 in Part B, prior enrollment and dosing in the C4591001 trial was mandatory). At enrollment into Part B of this trial, their participation in the C4591001 trial was terminated. Participants should have not had experienced COVID-19 based on medical history.
Key exclusion criteria (22 listed)
- Any existing condition which could have affected vaccine injection and/or assessment of local reactions assessment, e.g., tattoos, severe scars, etc.
- Any bleeding diathesis or condition associated with prolonged bleeding that could have, in the opinion of the investigator, contraindicated intramuscular injection.
- Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that, in the investigator's judgment, made the participant inappropriate for the trial.
- Any current febrile illness (body temperature ≥38.0°C/≥100.4°F) or other acute illness within 48 h prior to Day 1/IMP injection in this trial.
- Any current or history of cardiovascular diseases, e.g., myocarditis, pericarditis, myocardial infarction, congestive heart failure, cardiomyopathy or clinically significant arrhythmias, unless such disease was not considered relevant for participation in this trial in the investigator's judgment.
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 (IM) | Biological | Part A - Cohort 5: 18 to 55 years of age, Part C - Cohort 8: 18 to 85 years of age |
| Multivalent BNT162b2 (B.1.1.7 + B.1.617.2)Intramuscular (IM) | Biological | Part A - Cohort 1: 18 to 55 years of age, Part A - Cohort 2: 18 to 55 years of age, Part A - Cohort 6: 18 to 55 years of age, Part B - Cohort 1: 18 to 85 years of age, Part B - Cohort 6: 18 to 85 years of age |
| Monovalent BNT162b2 (B.1.1.7)Intramuscular (IM) | Biological | Part A - Cohort 3: 18 to 55 years of age |
| Monovalent BNT162b2 (B.1.617.2)Intramuscular (IM) | Biological | Part A - Cohort 4: 18 to 55 years of age, Part B - Cohort 4: 18 to 85 years of age |
| Monovalent BNT162b2 (B.1.1.529.1)Intramuscular (IM) | Biological | Part C - Cohort 7: 18 to 85 years of age |
| ObservationalNo vaccination within 3 months after Visit 1. | Other | Part C - Cohort 9: 18 to 85 years of age |
Primary outcome
All Parts - Percentage of Participants Reporting Local Reactions at the Injection Site (Pain, Tenderness, Erythema/Redness, Induration/Swelling)
Time frame: from Day 1 to Day 7 after each IMP dose
Local reactions of any grade are reported. Local reactions were graded using criteria based on the US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"; the guidance uses the Grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening). The reporting of systemic reactions was based on the participant's assessments collected in the electronic diary (e-diary) or mapped from the adverse event case report form from Day 1 to Day 7 after each IMP dose. For Erythema/redness and Induration/swelling, the reported size had to be at least 2.5 cm to be deemed as a local reaction. Local reactions with a size less than 2.5 cm are not included in the analysis. Subjects in Cohort 9 did not receive a vaccination and are not included in this analysis.
All Parts - Percentage of Participants Reporting Systemic Events (Fever, Fatigue, Headache, Chills, Vomiting, Nausea, Diarrhea, New or Worsened Muscle Pain, and New or Worsened Joint Pain)
Time frame: from Day 1 to Day 7 after each IMP dose
Systemic reactions of any grade are reported. Systemic reactions were graded using criteria based on the guidance given in the US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"; the guidance uses the Grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening). The reporting of systemic reactions was based on the participant's assessments collected in the e-diary or mapped from the adverse event case report form from Day 1 to Day 7 after each IMP dose. For Fever, the reported oral temperature had to be ≥38.0°C to be deemed as a systemic event. Oral temperature less than 38.0°C are not included in the analysis. Subjects in Cohort 9 did not receive a vaccination and are not included in this analysis.
All Parts - Percentage of Participants Reporting Adverse Events (AEs)
Time frame: Dose 1 up to 1 month after each dose (all parts)
An AE is defined as TEAE if the event onset date and time is after the first IMP dose (if the event was absent before the first administration of the IMP) or worsened after the first IMP dose (if the event was present before the first administration of the IMP). In the event of an incomplete onset date, the event is considered as treatment-emergent unless the partial onset date information or complete or partial end date confirms the onset date or the event end prior to the first dose of IMP. Percentages for dose 1, dose 2, dose 3 and overall summaries are based upon the number of participants who received the respective IMP dose.
All Parts - Percentage of Participants Reporting Serious Adverse Events (SAEs)
Time frame: Dose 1 up to 6 months after the last dose
An SAE was any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/ incapacity; was a congenital anomaly/birth defect and/or was another important medical event. SAEs from dose 1 up to 6 months post last IMP dose are presented. MedDRA (version 26.1) coding dictionary applied. An SAE is defined as TESAE if the event onset date and time is after the first IMP dose (if the event was absent before the first administration of the IMP) or worsened after the first IMP dose (if the event was present before the first administration of the IMP). In the event of an incomplete onset date, the event is considered as treatment-emergent unless the partial onset date information or complete or partial end date confirms the onset date or the event end prior to the first dose of IMP.
Part B - GMR of B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial
Time frame: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and vaccine group. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.1.7 and reference strain respectively at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which GMR was derived) were secondary endpoints and are presented in outcome measure 22. GMR = Geometric mean ratio; NT = neutralizing titers
Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial
Time frame: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.617.2 and reference strain respectively at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which GMR was derived) were secondary endpoints and are presented in outcome measure 22. GMR = Geometric mean ratio; NT = neutralizing titers
Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial
Time frame: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.617.2 and reference strain respectively at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which GMR was derived) were secondary endpoints and are presented in outcome measure 24.
Part B - Difference in Seroresponse (SR) to B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)
Time frame: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Seroresponse was defined as a ≥4-fold rise in neutralizing titer from baseline. For subjects with a baseline titer less than the lower limit of quantitation (<LLOQ), seroresponse was defined as a post-vaccination titer of ≥4× LLOQ. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in seroresponse data are presented below as per the primary endpoint defined in the protocol. Seroresponses for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 23.
Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)
Time frame: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Seroresponse was defined as a ≥4-fold rise in neutralizing titer from baseline. For subjects with a baseline titer less than the lower limit of quantitation (<LLOQ), seroresponse was defined as a post-vaccination titer of ≥4× LLOQ. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in seroresponse data are presented below as per the primary endpoint defined in the protocol. Seroresponses for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 23.
Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (NCT04368728)
Time frame: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Seroresponse was defined as a ≥4-fold rise in neutralizing titer from baseline. For subjects with a baseline titer less than the lower limit of quantitation (<LLOQ), seroresponse was defined as a post-vaccination titer of ≥4× LLOQ. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in seroresponse data are presented below as per the primary endpoint defined in the protocol. Seroresponses for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 25.
Part B - GMR of B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial
Time frame: 1 month
Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that the non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore, data were not available to calculate the GMR. Available GMT data for the 17 Cohort B6 participants without evidence of infection were analyzed and are presented in Outcome Measure 28.
Part B - GMR of B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial
Time frame: 1 month
Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that the non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore, data were not available to calculate the GMR. Available GMT data for the 17 Part B Cohort 6 participants without evidence of infection were analyzed and are presented in Outcome Measure 28.
Part B - The Difference in SR to B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial
Time frame: 1 month
Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore, data were not available to calculate difference in SR. Available SR data for the 17 Part B Cohort 6 participants without evidence of infection were analyzed and presented in Outcome Measure 31.
Part B - The Difference in SR to B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the C4591001 (NCT04368728) Trial
Time frame: 1 month
Cohort B6 aimed to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment of baseline samples. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control group (C4591001/NCT04368728). Procedurally, submission of a protocol amendment was not possible. However, the Statistical Analysis Plan was amended to describe that the non-inferiority analysis could not be performed according to the protocol. Control participants were not selected as planned; therefore data were not available to calculate difference in SR. Available SR data for the 17 Part B Cohort 6 participants without evidence of infection were analyzed and presented in Outcome Measure 31.
Part B - GMR of Reference Strain NT After One Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in Participants With Evidence of Prior Infection to the Reference Strain NT After 2 Doses of BNT162b2 in Participants Without Evidence of Infection
Time frame: 3 weeks post Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
GMR of reference strain NT 3 weeks (3W) after one dose (PD1) of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection to the reference strain NT 1 month after two doses of BNT162b2 in participants without evidence of infection (COVID-19 Vaccine-naïve Participants) from the Phase III trial C4591001 (NCT04368728). GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and corresponding CIs (based on the Student t distribution). Assay results below LLOQ were set to 0.5 × LLOQ. GMTs of NTs are presented in the descriptive data section of this outcome measure. GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of LS means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. GMR data are presented in the statistical analysis section.
Part B - The Difference in SRs to the Reference Strain NT in Subjects With Evidence of Prior Infection and to the Reference Strain NT in Participants Without Evidence of Infection (COVID-19 Vaccine-naïve Participants)
Time frame: 3 weeks post Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
The difference in SRs to the reference strain NT 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection to the reference strain NT 1 month after two doses of BNT162b2 in participants without evidence of infection from the Phase III trial C4591001 (NCT04368728). SR was defined as achieving a ≥4-fold rise from baseline. If the baseline measurement was below the LLOQ, a post-vaccination assay result ≥4 × LLOQ was considered a SR. SR to the reference strain NTs are presented in the descriptive data section of this outcome measure. Adjusted difference in proportions was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. 2-Sided CI was based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in SR data are presented in the statistical analysis section.
Part C - GMR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 and 8.
Time frame: 1 month after 1 dose of BNT162b2 or BNT162b2 (B.1.1.529.1)
GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age and number of prior doses. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.1.529.1 at the given dose/sampling time point within the specified window. GMR data are presented below as per the primary endpoint defined in the protocol. GMTs for the individual arms (from which the difference was derived) were secondary endpoints and are presented in outcome measure 32.
Part C - The Difference in SR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 & 8.
Time frame: 1 month after 1 dose of BNT162b2 or BNT162b2 (B.1.1.529.1)
SR was defined as a ≥4-fold rise in neutralizing titer from baseline. For participants with a baseline titer less than the lower limit of quantitation (<LLOQ), SR was defined as a post-vaccination titer of ≥4× LLOQ. SR to the reference strain NTs are presented in the descriptive data section of this outcome measure. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI were based on the Newcombe method with minimum risk weights for the difference in proportions. Difference in SR data are presented in the statistical analysis section.
14 secondary outcomes
Part A - Geometric Mean Titer (GMT) at Each Timepoint
Time frame: Day 1 up to Day 421
Part A - Geometric Mean Fold Rises (GMFR) From Before Vaccination to Each Subsequent Time Point After Vaccination
Time frame: Day 1 to Day 421
Part A - Percentage of Participants Achieving SR in Terms of NT at Each Post Vaccination Time Point
Time frame: Day 1 to Day 421
Part B - GMT of VOCs and Reference Strains in Part B Cohort 1 and Control
Time frame: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - SR of of VOCs and Reference Strains in Part B Cohort 1 and Control
Time frame: 1 month after Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - GMT of VOCs and Reference Strains in Part B Cohort 4 and Control
Time frame: 1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - SR of of VOCs and Reference Strains in Part B Cohort 4 and Control
Time frame: 1 month after Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (NCT04368728) trial
Part B - GMT of VOCs and Reference Strain in Part B Cohort 6 1 Month After Dose 2 and 1 Month After Dose 3
Time frame: 1 month after Dose 2 and 1 month after Dose 3
Part B - Cohort 6 - Percentages With SRs to VOCs (B.1.1.7, B.1.617.2) and Reference Strain
Time frame: 1 month after Dose 2 and 1 month after Dose 3
Part B - GMTs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection in Part B C6 (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection in Part B C1 (1 Booster Dose)
Time frame: Day 1 up to 1 month after 1 booster dose in Part B Cohort 1 without evidence of infection, up to 1 month after 2 doses in Part B Cohort 6 without evidence of infection and up to 3 weeks after 1 dose in Part B Cohort 6 with evidence of prior infection
Part B - GMRs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)
Time frame: Day 1 to Day 29
Part B - Difference in SRs to VOCs in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)
Time frame: Day 1 to Day 29
Part B - SR of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 Primary Doses Respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)
Time frame: 3 weeks after one dose in participants with evidence of prior infection (Cohort 6), 1 month after two doses in participants without evidence of infection (Cohort 6), and 1 month after one booster dose (Cohort 1)
Part C - GMT - B.1.1.529.1 in RNA Based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection
Time frame: Day 1 to Day 360
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39097927Muik A, Quandt J, Lui BG, Bacher M, Lutz S, Grunenthal M, Toker A, Grosser J, Ozhelvaci O, Blokhina O, Shpyro S, Vogler I, Salisch N, Tureci O, Sahin U. Immunity against conserved epitopes dominates after two consecutive exposures to SARS-CoV-2 Omicron BA.1. Cell Rep. 2024 Aug 27;43(8):114567. doi: 10.1016/j.celrep.2024.114567. Epub 2024 Aug 3.
- 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 36378074Muik A, Lui BG, Bacher M, Wallisch AK, Toker A, Couto CIC, Guler A, Mampilli V, Schmitt GJ, Mottl J, Ziegenhals T, Fesser S, Reinholz J, Wernig F, Schraut KG, Hefesha H, Cai H, Yang Q, Walzer KC, Grosser J, Strauss S, Finlayson A, Kruger K, Ozhelvaci O, Grikscheit K, Kohmer N, Ciesek S, Swanson KA, Vogel AB, Tureci O, Sahin U. Exposure to BA.4/5 S protein drives neutralization of Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5 in vaccine-experienced humans and mice. Sci Immunol. 2022 Dec 23;7(78):eade9888. doi: 10.1126/sciimmunol.ade9888. Epub 2022 Dec 23.
- Individual participant dataSharing planned: No
Related trials for SARS-CoV-2 Infection
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Active, not recruiting
Intervention to Address Disparate Mental Health Consequences of COVID-19 Pandemic on Latinx and African Newcomers
Mental Health Issue, Mental Health Disorder
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
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.
BioNTech Responsible Person study director
BioNTech SE
35 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BNT162b2, Multivalent BNT162b2 (B.1.1.7 + B.1.617.2) and Monovalent BNT162b2 (B.1.1.7) in people with SARS-CoV-2 Infection and COVID-19, run by BioNTech SE at 35 sites in 4 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 19 inclusion and 22 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 22 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, South Africa, Turkey (Türkiye), Germany. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 22 Nov 2024). 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?
All Parts - Percentage of Participants Reporting Local Reactions at the Injection Site (Pain, Tenderness, Erythema/Redness, Induration/Swelling) (time frame: from Day 1 to Day 7 after each IMP dose). The study lists 18 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 NCT05004181, which also lists 3 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 22 Nov 2024.