AzTrials
AzTrials

SARS-CoV InfectionPhase 2SARSNCT04761822

COVID19 SARS Vaccinations: Systemic Allergic Reactions to SARS-CoV-2 Vaccinations

A Phase 2 study testing Moderna COVID-19 Vaccine and Pfizer-BioNTech COVID-19 Vaccine in people with SARS-CoV Infection and COVID-19, run by National Institute of Allergy and Infectious Diseases (NIAID) at 29 sites in United States.

Completed

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

Official record
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Trial summary

Background: Allergic reactions have been reported to occur after vaccination with both the Pfizer-BioNTech COVID-19 Vaccine and Moderna COVID-19 Vaccine. Allergic reactions range from mild to severe and include life- threatening anaphylactic reactions, although no deaths have been reported with either vaccine. Read more about this study

Who is it for?
Ages 5 years and olderHealthy volunteers can take part
Conditions the study is for
SARS-CoV Infection, COVID-19, Allergic Reaction
What is being tested?
Moderna COVID-19 Vaccine and Pfizer-BioNTech COVID-19 Vaccine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
746 participants
Where
29 sitesUnited States
Study dates
7 Apr 2021to 27 Apr 2022
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 5 years and older
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

  • Individuals who meet all of the following criteria are eligible for enrollment as study participants:
  • Both groups (e.g., High-Allergy and Mast Cell Disorder (HA/MCD) Group and Comparison Group):
  • Able to understand and provide informed consent
  • Male or non-pregnant female ≥12 years of age on the date of first study vaccination/placebo administration (protocol versions 1.0 - 4.0) OR male or non-pregnant female 5-17 years of age on the date of first study vaccination/placebo administration (protocol version 5.0)
  • Females of childbearing potential must have a negative pregnancy test prior to the first vaccination and placebo administration, if applicable.
  • --If a participant becomes pregnant after receiving a placebo dose but prior to receiving study vaccination, she will be discontinued from the study
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  • Females of reproductive potential° and sexually active must agree to use FDA approved methods of birth control for the duration of the study. These include hormonal contraceptives, intrauterine device, double barrier contraception (i.e., condom plus diaphragm), or male partner with documented vasectomy.
  • Menopause is defined as at least 12 consecutive months without menses; if in question, a follicle stimulating hormone of ≥25 U/mL must be documented.
  • Hysterectomy, bilateral oophorectomy, or bilateral tubal ligation must be documented, as applicable; if documented, women with these conditions are not required to use additional contraception.
  • High-Allergy and Mast Cell Disorder (HA/MCD) Group:
  • Individuals who meet at least one of the following criteria are eligible for enrollment in the HA/MCD group:
  • History of a severe allergic reaction to food(s), allergen immunotherapy, insect venom(s), or latex with use of epinephrine within the last 15 years
  • History of an Emergency Department visit with convincing evidence of a systemic allergic reaction (consistent with CoFAR Grade 3 or higher) to food(s), allergen immunotherapy, insect venom(s), or latex within the last 15 years
  • History of documented, immediate allergic reactions to 2 or more unrelated drugs within the last 15 years
  • A convincing clinical history, or a history that is accompanied by a positive skin test, of an immediate reaction to a drug, vaccine, or latex within the last 15 years
  • History of physician-diagnosed idiopathic anaphylaxis requiring epinephrine or an Emergency Department visit in the last 15 years
  • History of a physician-diagnosed mast cell disorder (e.g., mastocytosis, mast cell activation syndrome [MCAS], or hereditary alpha-tryptasemia). MCAS must meet consensus criteria as defined below:
  • Criterion A: Typical clinical signs of severe, recurrent (episodic) systemic Mast Cell Activation are present (often in form of anaphylaxis)
  • ---Definition of systemic: involving at least 2 organ systems
  • Criterion B: Involvement of Mast Cell (MC) is documented by biochemical studies
  • --- Preferred marker: increase in serum tryptase level from the individual's baseline to plus 20% + 2 ng/ml
  • Criterion C: Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production or drugs blocking mediator release or effects of MC-derived mediators
  • NOTE: All 3 Mast Cell Activation Syndrome (MCAS) criteria (A + B + C) must be fulfilled to call a condition MCAS.
  • Comparison Group:
  • Individuals who meet all of the following criteria are eligible for enrollment in the comparison group:
  • No history of allergic asthma or atopic dermatitis within the last 10 years
  • No history of chronic spontaneous urticaria, or angioedema
  • No history of allergic reactions to foods or insect venoms
  • No history of allergic reactions to drugs or vaccines
  • No history of anaphylaxis
  • No history of a mast cell disorder (e.g., mastocytosis, mast cell activation syndrome [MCAS], or hereditary alpha- tryptasemia)

Who cannot join

  • Individuals who meet any of these criteria are not eligible for enrollment as study participants:
  • Inability or unwillingness of a participant and/or parent/legal guardian to give written informed consent and/or assent, as applicable, or to comply with study protocol
  • Weight less than 15 kg (33 lbs)
  • Prior receipt of any doses of the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) Vaccine, Moderna COVID-19 Vaccine, or any other COVID-19 vaccine
  • History of a severe reaction to any component of the Pfizer-BioNTech COVID-19 Vaccine or Moderna COVID-19 Vaccine
  • History of contact dermatitis with confirmed patch test reaction to Prevalence of polyethylene glycol (PEG)
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  • History of reaction to Doxil®
  • Known exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and still within the quarantine window
  • Symptoms consistent with acute COVID-19 infection or known COVID-19 infection (positive Polymerase chain reaction [PCR] or antigen test) and still within the quarantine window
  • Have an acute illness, including body temperature greater than 100.4 degrees Fahrenheit, within 14 days of the first study vaccination/placebo administration or 3 days prior to each subsequent vaccination
  • History of autoimmune or other disorders requiring systemic immune modulators
  • History of acute urticaria within 28 days of randomization
  • Pregnant
  • Have received any vaccines within 14 days of the first study vaccination/placebo administration or plan to receive other vaccines during the study period
  • Had any allergen immunotherapy administration within 24 hours prior to vaccination/placebo administration or plan to receive within 24 hours after vaccination/placebo administration
  • Have received a biologic therapy within 6 months of randomization
  • Use of systemic steroids for any reason within 28 days of randomization
  • Use of Zileuton® within 14 days of randomization
  • Use of any monoclonal antibody agent for treatment or prevention of COVID-19 within 3 months of randomization
  • Coronary artery disease, peripheral or cerebral vascular disease, unstable angina, or cardiac arrhythmia, other than supraventricular tachycardia (SVT)
  • Medically unstable hypertension
  • Current use of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, monoamine oxidase (MAO) inhibitors, tricyclic anti-depressants or other agents that could interfere with the treatment of anaphylaxis, in the opinion of the investigator
  • Unstable asthma within 3 months of randomization or symptomatic asthma on the day of vaccination, as assessed by the site investigator
  • Have past or current medical problems or findings from physical exam or laboratory testing not listed above, which in the opinion of the investigator, may pose additional risks from participation in the study or which may interfere with the ability to comply with study requirements --This includes individuals with underlying conditions or other medications that, in the opinion of the investigator, may increase risk in the event of an anaphylactic reaction or lead to complications following administration of epinephrine

Trial locations and contacts

29 sites in 1 country.

29 sites in 1 country

United States29 sites

  • University of Michigan Health

    Ann Arbor, Michigan, 48109

  • Emory University School of Medicine, Emory Healthcare: Emory Clinic Allergy and Immunology

    Atlanta, Georgia, 30324

  • Johns Hopkins Bayview Medical Center

    Baltimore, Maryland, 21224

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • North Carolina Translational and Clinical Sciences Institute-Clinical & Translational Research Center (CTRC) at the University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • University of Virginia Health System: Department of Medicine, Division of Allergy and Immunology

    Charlottesville, Virginia, 22908

  • Sinus and Allergy Center of Northwestern University

    Chicago, Illinois, 60611

  • Cleveland Clinic, Allergy & Clinical Immunology

    Cleveland, Ohio, 44195

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • National Jewish Health

    Denver, Colorado, 80206

  • Henry Ford Hospital and Health System

    Detroit, Michigan, 48202

  • Penn State Health Allergy, Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Baylor College of Medicine Medical Center

    Houston, Texas, 77030

  • University of Iowa Health Care

    Iowa City, Iowa, 52242

  • Arkansas Children's, University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72202

  • University of California, Los Angeles Medical Center

    Los Angeles, California, 90095

  • University of Wisconsin Asthma Allergy Pulmonary Research

    Madison, Wisconsin, 53792

  • University Health, University of Miami Health System

    Miami, Florida, 33136

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Mount Sinai Hospital, Department of Medicine, Division of Clinical Immunology

    New York, New York, 10029

  • Columbia University Irving Medical Center

    New York, New York, 10032

  • Virginia Commonwealth University, Department of Internal Medicine, Division of Rheumatology, Allergy & Immunology

    Richmond, Virginia, 23298

  • Rochester Regional Health

    Rochester, New York, 14607

  • NorthShore University HealthSystem, Dermatology Clinical Trials Unit

    Skokie, Illinois, 60077

  • Saint Louis University Care Center for Specialized Medicine

    St Louis, Missouri, 63104

  • Stanford Medicine, Sean N. Parker Center for Allergy & Asthma Research

    Stanford, California, 94040

  • University of South Florida Asthma Allergy and Immunology Clinical Research Unit

    Tampa, Florida, 33613

  • University of Arizona Health Sciences, College of Medicine Tucson, Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine

    Tucson, Arizona, 85724

Other trials in United States

About this study

Official title: Systemic Allergic Reactions to SARS-CoV-2 Vaccination

Background: Allergic reactions have been reported to occur after vaccination with both the Pfizer-BioNTech COVID-19 Vaccine and Moderna COVID-19 Vaccine. Allergic reactions range from mild to severe and include life- threatening anaphylactic reactions, although no deaths have been reported with either vaccine.

This study is designed with two principal aims:

  • To estimate the proportions of systemic allergic reactions to the Pfizer-BioNTech COVID-19 Vaccine and the Moderna COVID-19 Vaccine in a High-Allergy/Mast Cell Disorder (HA/MCD) population, and
  • If the risk in the HA/MCD is demonstrable, to determine whether the proportions are higher in the HA/MCD in comparison to a representative population without severe allergies or mast cell disorders
Read the detailed description

This is a multicenter, randomized, initially blinded (masked), phase 2 trial to assess SARS-CoV-2 vaccination reactions in two populations:

  • One population including individuals with a history of allergic reactions or Mast Cell Disorder (HA/MCD), and
  • One comparison population without severe allergies or mast cell disorders.

Approximately 2040 HA/MCD and 1360 comparison participants will be enrolled across participating sites in the United States. Approximately two-thirds of participants enrolled in each of the 2 groups will be female. This is because the vast majority of cases of anaphylaxis to the COVID-19 vaccines have occurred in women. Enrollment of participants who qualify only on the basis of reactions to multiple unrelated drugs will be limited to approximately 300.

Enrollment of the MCD group is anticipated to be at least 200 participants, and not more than 300 participants.

Participants in each population will be randomized 2:2:1:1 to receive the Pfizer-BioNTech COVID-19 Vaccine, Moderna COVID-19 Vaccine, placebo + Pfizer-BioNTech COVID-19 Vaccine, or placebo + Moderna COVID-19 Vaccine, if enrolled in the initial study period under protocol versions 1.0 -4.0. Participants enrolled under protocol version 5.0 will be randomized 2:1 to receive the Pfizer-BioNTech COVID-19 Vaccine or placebo + Pfizer-BioNTech COVID-19 Vaccine. If enrollment under protocol version 5.0 is robust and sustained, the active vaccine randomization may be changed to the Moderna COVID-19 Vaccine.

Participants randomized to one of the placebo groups will receive placebo as a first dose and will receive two doses of their assigned active vaccine at subsequent visits. During the first visit, all participants will be initially-blinded to whether they are receiving placebo or vaccine, and to which vaccine they are receiving (if enrolling under protocol versions 1.0 -4.0).

Due to the different dosing schedules for the Pfizer-BioNTech COVID-19 Vaccine and Moderna COVID-19 Vaccine, it will become apparent to both the site staff and the study participant which vaccine has been assigned, once the second injection visit is scheduled. However, the blind over placebo versus vaccine will remain in effect until after the second visit. During a follow-up call, scheduled 3 days after the second injection, participants will be unblinded as to whether they received placebo or active vaccine.

However under protocol version 5.0, participants will be told if they received placebo as the first injection during the following up conducted 3 days after. Participants in this phase of the study will also know which company's vaccine they are receiving, as the vaccines are anticipated to be used sequentially and will also be noted in the consent form.

Study Duration: Randomized and vaccinated participants will complete study participation in approximately 29 days if vaccinated with the Pfizer-BioNTech COVID-19 Vaccine, 36 days if vaccinated with the Moderna COVID-19 Vaccine. Participants enrolled under protocol versions 1.0 -4.0 will complete study participation in 50 or 64 days if administered placebo before receiving two doses of either the Pfizer-BioNTech COVID-19 Vaccine or the Moderna COVID-19 Vaccine, respectively and participants enrolled under protocol version 5.0 will complete participation in approximately 36 of 43 days, respectively, if they receive placebo first.

Being tested
Moderna COVID-19 Vaccine, Pfizer-BioNTech COVID-19 Vaccine, Placebo
Keywords
SARS-CoV-2 vaccination, COVID-19 vaccination, Systemic Allergic Reactions to SARS-CoV-2 vaccination
Medical subject headings
Severe Acute Respiratory Syndrome, COVID-19, Hypersensitivity, Mastocytosis

What participants receive

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

  • Moderna COVID-19 VaccineBiological

    Also called mRNA-1273

    Intramuscular injection

  • Pfizer-BioNTech COVID-19 VaccineBiological

    Also called BNT162b2

    Intramuscular injection

  • PlaceboBiological

    Also called sterile, preservative-free 0.9% Sodium Chloride Injection

    Intramuscular injection

Study groups in NCT04761822
Study groupRoleWhat they receive
Moderna COVID-19 VaccineExperimentalThe Moderna COVID-19 Vaccine (0.5 mL) will be administered intramuscularly in the deltoid, as a series of two doses (0.5 mL each) administered 1 month (28 days) apart.
Receives: Biological: Moderna COVID-19 Vaccine
Pfizer-BioNTech COVID-19 VaccineExperimentalThe Pfizer-BioNTech COVID-19 Vaccine (0.3 mL) will be administered intramuscularly in the deltoid, as a series of two doses (0.3 mL each) administered 3 weeks (21 days) apart.
Receives: Biological: Pfizer-BioNTech COVID-19 Vaccine
Placebo +Moderna COVID-19 VaccineExperimentalParticipants will receive placebo as a first dose followed by two doses of their assigned active vaccine at subsequent visits. 0.5 mL of placebo will be administered intramuscularly in the deltoid. The placebo dose will be followed by two doses of Moderna COVID-19 Vaccine, with the first dose administered 1 month later. The Moderna COVID-19 Vaccine (0.5 mL) will be administered intramuscularly in the deltoid, as a series of two doses (0.5 mL each) administered 1 month (28 days) apart.
Receives: Biological: Moderna COVID-19 Vaccine; Biological: Placebo
Placebo+Pfizer-BioNTech COVID-19 VaccineExperimentalParticipants will receive placebo as a first dose followed by two doses of their assigned active vaccine at subsequent visits. 0.3 mL of placebo will be administered intramuscularly in the deltoid. The placebo dose will be followed by two doses of Pfizer-BioNTech COVID-19 Vaccine, with the first dose administered 1 month later. The Pfizer-BioNTech COVID-19 Vaccine (0.3 mL) will be administered intramuscularly in the deltoid, as a series of two doses (0.3 mL each) administered 3 weeks (21 days) apart.
Receives: Biological: Pfizer-BioNTech COVID-19 Vaccine; Biological: Placebo

What is being measured

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

  1. Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+ Regardless of Tryptase or CoFAR Grade 1 With Elevated Tryptase) Within 90 Minutes Post-vaccination to Either Dose of Pfizer-BioNTech COVID-19 Vaccine.

    Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Tryptase is an enzyme released into the blood during an allergic reaction. An elevation in tryptase is defined as a value that is higher than 1.2 x the baseline tryptase plus 2 ng/ml. Subjects who did not receive their second dose of the vaccine were not included unless they reacted (per the endpoint) to the first dose. The comparison is between the High Allergy/Mast Cell Disorder and Comparison populations.

    Measured: Within the 90-minute post-vaccination observation period to either dose of the Pfizer-BioNTech COVID-19 Vaccine.

  2. Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+ Regardless of Tryptase or CoFAR Grade 1 With Elevated Tryptase) Within 90 Minutes Post-vaccination to Either Dose of the Moderna COVID-19 Vaccine.

    Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Tryptase is an enzyme released into the blood during an allergic reaction. An elevation in tryptase is defined as a value that is higher than 1.2 x the baseline tryptase plus 2 ng/ml. Subjects who did not receive their second dose of the vaccine were not included unless they reacted (per the endpoint) to the first dose. The comparison is between the High Allergy/Mast Cell Disorder and Comparison populations.

    Measured: Within the 90-minute post-vaccination observation period to either dose of the Moderna COVID-19 Vaccine.

Secondary outcomes (12)

  1. The Proportion of Participants Who Experienced a Severe (CoFAR Grade 3+) Systemic Allergic Reaction Within 90 Minutes Post-vaccination to Either Dose of the Pfizer-BioNTech COVID-19 Vaccine.

    Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Subjects who did not receive their second dose of the vaccine were not included unless they reacted (per the endpoint) to the first dose. The comparison is between the High Allergy/Mast Cell Disorder and Comparison populations.

    Measured: Within the 90-minute post-vaccination observation period to either dose of the Pfizer-BioNTech COVID-19 Vaccine.

  2. The Proportion of Participants Who Experienced a Severe (CoFAR Grade 3+) Systemic Allergic Reaction Within the 90-minute Post-vaccination Observation Period to Either Dose of the Moderna COVID-19 Vaccine.

    Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Subjects who did not receive their second dose of the vaccine were not included unless they reacted (per the endpoint) to the first dose. The comparison is between the High Allergy/Mast Cell Disorder and Comparison populations.

    Measured: Within the 90-minute post-vaccination observation period to either dose of the Moderna COVID-19 Vaccine.

  3. The Proportion of Participants Who Experienced an Anaphylactic Reaction Per Brighton Collaboration Criteria (Levels 1-3) Within 90 Minutes Post-vaccination to Either Dose of the Pfizer-BioNTech COVID-19 Vaccine.

    Allergic reactions were graded using the Brighton Collaboration Criteria. The scale ranges from level 1 through 3. Level 1 represents the highest level of diagnostic certainty that a reported case is anaphylaxis, levels 2 and 3 represent successively lower levels of diagnostic certainty. Subjects who did not receive their second dose of the vaccine were not included unless they reacted (per the endpoint) to the first dose. The comparison is between the High Allergy/Mast Cell Disorder and Comparison populations.

    Measured: Within the 90-minute post-vaccination observation period to either dose of the Pfizer-BioNTech COVID-19 Vaccine.

  4. The Proportion of Participants Who Experienced an Anaphylactic Reaction Per Brighton Collaboration Criteria (Levels 1-3) Within 90 Minutes Post-vaccination to Either Dose of the Moderna COVID-19 Vaccine.

    Allergic reactions were graded using the Brighton Collaboration Criteria. The scale ranges from level 1 through 3. Level 1 represents the highest level of diagnostic certainty that a reported case is anaphylaxis, levels 2 and 3 represent successively lower levels of diagnostic certainty. Subjects who did not receive their second dose of the vaccine were not included unless they reacted (per the endpoint) to the first dose. The comparison is between the High Allergy/Mast Cell Disorder and Comparison populations.

    Measured: Within the 90-minute post-vaccination observation period to either dose of the Moderna COVID-19 Vaccine.

  5. Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+ Regardless of Tryptase or CoFAR Grade 1 With Elevated Tryptase) Within 90 Minutes Post-vaccination to the First Dose of the Pfizer-BioNTech COVID-19 Vaccine.

    Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Tryptase is an enzyme released into the blood during an allergic reaction. An elevation in tryptase is defined as a value that is higher than 1.2 x the baseline tryptase plus 2 ng/ml. The comparison is between the participants who received active vaccine as their first, fully blinded, injection (assigned to the Pfizer-BioNTech COVID-19 Vaccine arm) and participants who received their first active vaccine as their second injection (assigned to the Placebo + Pfizer-BioNTech COVID-19 Vaccine arm). Due to the design of the trial, participants would have understood that the second dose in any arm must be an active vaccination.

    Measured: Within the 90-minute post-vaccination observation period to the first dose of the Pfizer-BioNTech COVID-19 Vaccine.

  6. Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+ Regardless of Tryptase or CoFAR Grade 1 With Elevated Tryptase) Within 90 Minutes Post-vaccination to the First Dose of the Moderna COVID-19 Vaccine.

    Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Tryptase is an enzyme released into the blood during an allergic reaction. An elevation in tryptase is defined as a value that is higher than 1.2 x the baseline tryptase plus 2 ng/ml. The comparison is between the participants who received active vaccine as their first, fully blinded, injection (assigned to the Moderna COVID-19 Vaccine arm) and participants who received their first active vaccine as their second injection (assigned to the Placebo + Moderna COVID-19 Vaccine arm). Due to the design of the trial, participants would have understood that the second dose in any arm must be an active vaccination.

    Measured: Within the 90-minute post-vaccination observation period to the first dose of the Moderna COVID-19 Vaccine.

  7. Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+ Regardless of Tryptase or CoFAR Grade 1 With Elevated Tryptase) Within 90 Minutes Post-vaccination to the Second Dose of the Pfizer-BioNTech COVID-19 Vaccine.

    Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Tryptase is an enzyme released into the blood during an allergic reaction. An elevation in tryptase is defined as a value that is higher than 1.2 x the baseline tryptase plus 2 ng/ml. The comparison is between the participants who received the second active vaccine as their second injection (assigned to the Pfizer-BioNTech COVID-19 Vaccine arm) and participants who received the second active vaccine as their third injection (assigned to the Placebo + Pfizer-BioNTech COVID-19 Vaccine arm). This comparison is conditional on there being no systemic allergic reaction to the first dose.

    Measured: Within the 90-minute post-vaccination observation period to the second dose of the Pfizer-BioNTech COVID-19 Vaccine.

  8. Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+ Regardless of Tryptase or CoFAR Grade 1 With Elevated Tryptase) Within 90 Minutes Post-vaccination to the Second Dose of the Moderna COVID-19 Vaccine.

    Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale is ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Tryptase is an enzyme released into the blood during an allergic reaction. An elevation in tryptase is defined as a value that is higher than 1.2 x the baseline tryptase plus 2 ng/ml. The comparison is between the participants who received the second active vaccine as their second injection (assigned to the Moderna COVID-19 Vaccine arm) and participants who received the second active vaccine as their third injection (assigned to the Placebo + Moderna COVID-19 Vaccine arm). This comparison is conditional on there being no systemic allergic reaction to the first dose.

    Measured: Within the 90-minute post-vaccination observation period to the second dose of the Moderna COVID-19 Vaccine.

  9. The Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+ Regardless of Tryptase or CoFAR Grade 1 With Elevated Tryptase) Within 90 Minutes Post-vaccination to the First Dose, Adjusting for Placebo.

    Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Tryptase is an enzyme released into the blood during an allergic reaction. An elevation in tryptase is defined as a value that is higher than 1.2 x the baseline tryptase plus 2 ng/ml. The comparison is between participants who had placebo as their first injection (either vaccine) and participants who had Pfizer-BioNTech COVID-19 Vaccine as their first injection. The comparison only includes subjects in the HA/MCD cohort.

    Measured: Within the 90-minute post-vaccination observation period to the first injection (placebo or active).

  10. The Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+ Regardless of Tryptase or CoFAR Grade 1 With Elevated Tryptase) Within 90 Minutes Post-vaccination to the First Dose, Adjusting for Placebo.

    Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale is ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Tryptase is an enzyme released into the blood during an allergic reaction. An elevation in tryptase is defined as a value that is higher than 1.2 x the baseline tryptase plus 2 ng/ml. The comparison is between participants who had placebo as their first injection and participants who had Moderna COVID-19 Vaccine as their first injection. The comparison only includes subjects in the HA/MCD cohort.

    Measured: Within the 90-minute post-vaccination observation period to the first injection.

  11. The Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+) Within 48-hours Post-vaccination to Either Dose of the Pfizer-BioNTech COVID-19 Vaccine.

    Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Subjects who did not receive their second dose of the vaccine were not included unless they reacted (per the endpoint) to the first dose. The comparison is between the High Allergy/Mast Cell Disorder and Comparison populations.

    Measured: After the 90 minute observation period to 48-hours post-vaccination to either dose of the Pfizer-BioNTech COVID-19 Vaccine.

  12. The Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+) Within 48-hours Post-vaccination to Either Dose of the Moderna COVID-19 Vaccine.

    Allergic reactions were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale ranges from grade 1 through 5. The higher the grade, the more severe the allergic reaction. Subjects who did not receive their second dose of the vaccine were not included unless they reacted (per the endpoint) to the first dose. The comparison is between the High Allergy/Mast Cell Disorder and Comparison populations.

    Measured: After the 90 minute observation period to 48-hours post-vaccination to either dose of the Moderna COVID-19 Vaccine.

Timeline

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

  1. First posted21 Feb 2021
  2. Study start7 Apr 2021
  3. Primary completion20 Apr 2022
  4. Study completion27 Apr 2022

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
746 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04761822
Sponsor's protocol ID
DAIT COVID-19-004
Other IDs
NIAID CRMS ID#: 38814
Acronym
SARS
Status last verified
Jul 2025
First submitted
17 Feb 2021
Last updated
12 Aug 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Participant level data access and additional relevant materials will be made available upon completion of the trial.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Moderna COVID-19 Vaccine and Pfizer-BioNTech COVID-19 Vaccine in people with SARS-CoV Infection and COVID-19, run by National Institute of Allergy and Infectious Diseases (NIAID) at 29 sites in United States.

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 24 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 12 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in United States. 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 15 Jun 2023). 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?

Proportion of Participants Who Experienced a Systemic Allergic Reaction (CoFAR Grade 2+ Regardless of Tryptase or CoFAR Grade 1 With Elevated Tryptase) Within 90 Minutes Post-vaccination to Either Dose of Pfizer-BioNTech COVID-19 Vaccine. (time frame: Within the 90-minute post-vaccination observation period to either dose of the Pfizer-BioNTech COVID-19 Vaccine.). The study lists 2 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 NCT04761822.

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 12 Aug 2025.

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