Systemic Allergic ReactionPhase 2NCT04977479
The Safety of Administering a Second Dose of a COVID-19 mRNA Vaccine in Individuals Who Experienced a Systemic Allergic Reaction to an Initial Dose
A Phase 2 study testing Pfizer-BioNTech COVID-19 Vaccine (Comirnaty) and Pfizer-BioNTech COVID-19 Vaccine, Bivalent in people with Systemic Allergic Reaction, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: Some people have allergic reactions to COVID-19 mRNA vaccines. Researchers want to learn more about these reactions to provide guidance on who can safely receive the vaccines, including a second dose in people who had a reaction to the first. Read more about this study
- Who is it for?
- Ages 16 to 69 years
- Conditions the study is for
- Systemic Allergic Reaction
- What is being tested?
- Pfizer-BioNTech COVID-19 Vaccine (Comirnaty) and Pfizer-BioNTech COVID-19 Vaccine, Bivalent
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Sep 2021to 22 Feb 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 16 to 69 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Ability to provide informed consent.
- Stated willingness to comply with all study procedures (including discontinuing medications as needed and availability for the duration of the study.
- Aged 16-69 years.
- Must have experienced a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2 ng/mL] per modified CoFAR Grading Scale for Systemic Allergic Reactions Version 3.0) to the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine. Patients without documented hypoxia, hypotension, or evidence of end-organ damage who were treated with epinephrine infusion would be considered as CoFAR Grade 3 reaction and may be eligible per investigator discretion.
- Must be at least 28 days out from their first dose of the Moderna vaccine or 21 days from their first dose of the Pfizer-BioNTech vaccine before proceeding with the placebo or vaccine challenge in this study.
- Have a primary care physician or other health care provider who will manage their medical care outside of this study.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Experienced a Grade 4 systemic allergic reaction (per CoFAR Grading Scale for Systemic Allergic Reactions Version 3.0) to the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine.
- Known exposure to SARS-CoV-2 and still within the quarantine window.
- Symptoms consistent with acute COVID-19 infection or known COVID-19 infection (positive reverse transcription-polymerase chain reaction [RT-PCR] or antigen test) and still within the quarantine window
- Have an acute illness, including body temperature greater than 100.4 degrees F, within 14 days prior to enrollment.
- History of autoimmune or other disorders requiring systemic immune modulators.
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- Are moderately or severely immunocompromised.
- History of acute urticaria within 28 days prior to enrollment.
- Pregnant.
- Have received any vaccines within 14 days prior to enrollment.
- Scheduled or planned receipt of approved or experimental vaccine prior to visit 3.
- Had any allergen immunotherapy administration within 24 hours prior to the first study vaccination or plan to receive within 24 hours after the second study vaccination.
- Have received a biological therapy within 6 months prior to enrollment.
- Use of systemic steroids for any reason within 28 days prior to enrollment.
- Use of zileuton within 14 days prior to enrollment.
- Use of EUA monoclonal antibodies casirivimab and indevimab, or bamlanivimab, or any other antibody agent for treatment or prevention of COVID-19 within 3 months of randomization.
- Presence of condition(s) that, in the judgment of the investigator or the referring physician, may put the participant at undue risk or make them unsuitable for participation in the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Randomized, Placebo-controlled Crossover Study to Assess the Safety of Administering a Second Dose of a COVID-19 mRNA Vaccine in Individuals Who Experienced a Systemic Allergic Reaction to an Initial Dose
Background:
Some people have allergic reactions to COVID-19 mRNA vaccines. Researchers want to learn more about these reactions to provide guidance on who can safely receive the vaccines, including a second dose in people who had a reaction to the first.
Read more
Objective:
To study the safety of giving a second mRNA COVID-19 vaccine dose to people who had a systemic allergic reaction to their first dose.
Eligibility:
People aged 16-69 who had a systemic allergic reaction to their first dose of COVID-19 vaccine.
Design:
Individuals who have underlying health issues may need to come to the NIH for screening tests to make sure they are safe to receive the vaccine. People who are eligible to participate in the study will be admitted to the NIH hospital and stay for at least 4 days. They will give urine samples. They will have a nasal swab SARS-CoV-2 test. They will have an intravenous line placed in each arm. They will get the study vaccine (Pfizer-BioNTech COVID-19 vaccine) and one dose of placebo on different days. They will have breathing tests. They may have clinical photography if they develop a rash.
Participants will have 4 follow-up visits - 2 by phone and 2 in-person visits at the NIH campus . They will have allergy skin testing at one visit. Drops of different allergens or controls will be placed on their back or arm. The skin under each drop will be scratched with a tool. If the results are negative, a small amount of allergen will be injected just below the surface of their skin. Participants who have no or only a mild allergic reaction to the second dose of the vaccine may be eligible to receive a Booster dose at the NIH.
Participation will last for approximately 5 months.
Read the detailed description
Study Description:
This is a single-site study to determine the safety of administering a dose of the Pfizer-BioNTech mRNA coronavirus disease 2019 (COVID-19) vaccine (Comirnaty) to individuals who experienced a systemic allergic reaction to their first full dose of the same vaccine or the Moderna mRNA vaccine, and to investigate possible mechanisms underlying allergic reactions.
Objectives:
Primary Objective:
- Assess the proportion of participants who develop a systemic allergic reaction (Consortium for Food Allergy Research grade 2 reaction and above regardless of tryptase, or CoFAR grade 1 with elevated tryptase [1.2 X baseline plus 2ng/mL]) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine.
Secondary Objectives:
- Assess the proportion of participants who develop a severe systemic allergic reaction (CoFAR Grade 3 reaction or higher regardless of tryptase) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine.
- Assess the proportion of participants who develop a mild-moderate allergic reaction (CoFAR Grade 1 or 2 reaction regardless of tryptase) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine.
- Assess the proportion of participants with anaphylactic reactions (Levels 1-3) per Brighton Collaboration Criteria (see Appendix B) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine.
- Assess the proportion of participants who develop a systemic allergic reaction (CoFAR Grade 2 reaction or higher regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine compared to the rate of these reactions following placebo administration.
- Compare the severity of allergic reactions to the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine to the severity of the reaction following administration of a subsequent dose of the Pfizer-BioNTech vaccine in individuals who experienced a systemic allergic reaction (CoFAR grade 2 reaction and above regardless of tryptase, or CoFAR grade 1 with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine.
Exploratory Objectives:
- Assess the risk of having a systemic allergic reaction to a dose of the Pfizer-BioNTech COVID-19 vaccine in participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the same vaccine or the Moderna COVID-19 according to baseline covariates.
- Examine possible mechanisms of allergic reactions to mRNA-based COVID-19 vaccines.
- Assess innate and adaptive immune responses, including functional antibody levels, to the Pfizer-BioNTech COVID-19 vaccine
- Investigate mental health characteristics of participants who experience an allergic reaction to the COVID-19 vaccine.
- Assess psychological impact of allergic reactions to the COVID-19 vaccine and examine changes in stress levels over time.
- Assess anxiety levels in participants and examine changes in anxiety over time.
- Assess the proportion of participants who experience no reaction or only a mild reaction (CoFAR Grade 2 or below) to a booster dose of the Pfizer-BioNTech vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2 ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine and no allergic reaction or a mild reaction (CoFAR Grade 2 or below) to a subsequent (second) dose of the Pfizer-BioNTech vaccine.
- Assess the development of autoantibodies after COVID-19 vaccination.
Endpoints:<TAB>
Primary Endpoint:
- The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who experience a systemic allergic reaction (CoFAR Grade 2 and above reaction regardless of tryptase, or CoFAR grade 1 with elevated tryptase [1.2 X baseline plus 2ng/mL]) within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine.
Secondary Endpoints:
- The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who experience a severe systemic allergic reaction (CoFAR grade 3 reaction and above) within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine.
- The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who experience a mild-moderate allergic reaction (CoFAR grade 1 or 2 reaction regardless of tryptase) within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine.
- The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who experience an anaphylactic reaction (Levels 1-3) per Brighton Collaboration Criteria within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine.
- The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who experience a systemic allergic reaction (CoFAR grade 2 reaction and above regardless of tryptase, or CoFAR grade 1 with elevated tryptase [1.2 X baseline plus 2ng/mL]) within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine compared to the rate of these reactions following placebo administration.
- The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who develop a lower or higher grade allergic reaction within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine.
Exploratory Endpoints:
- Prevalence of polyethylene glycol (PEG) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in each participant at baseline.
- Changes in anti-PEG and SARS-CoV-2 antibodies in each participant approximately 1 and 5 months after receiving the dose of the Pfizer-BioNTech vaccine administered on study.
- Prevalence of positive skin testing to the vaccine and/or vaccine components including PEG- and polysorbate 80-containing medications.
- Changes in biomarkers from baseline to post-dose of the Pfizer-BioNTech vaccine administered on study (e.g., known mediators of systemic reactions due to mast cell activation, markers of inflammatory response, markers of basophil and neutrophil activation, markers associated with activation of the classical and alternative complement pathways or kinin system, proteomics, metabolomics).
- Changes in blood transcriptomics after vaccination.
- Changes in innate and adaptive immune responses including functional antibody levels after vaccination.
- Mental health/anxiety questionnaire scores and anxiety level ratings at baseline.
- Results of psychiatric consultation/mental health interview.
- Changes in mental health/anxiety questionnaire scores and anxiety level ratings over the study period.
- The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2 ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine and no allergic reaction or a mild reaction (CoFAR Grade 2 or below) to a subsequent (second) dose of the Pfizer-BioNTech vaccine who experience no reaction or only a mild reaction (CoFAR Grade 2 or below) to a booster dose of the Pfizer-BioNTech vaccine administered approximately 5 months after the second dose.
- Changes in blood transcriptomics after vaccination.
- Changes in innate and adaptive immune responses including functional antibody levels after vaccination.
- Mental health/anxiety questionnaire scores and anxiety level ratings at baseline.
- Results of psychiatric consultation/mental health interview.
- Changes in mental health/anxiety questionnaire scores and anxiety level ratings over the study period.
- The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2 ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine and no allergic reaction or a mild reaction (CoFAR Grade 2 or below) to a subsequent (second) dose of the Pfizer-BioNTech vaccine who experience no reaction or only a mild reaction (CoFAR Grade 2 or below) to a booster dose of the Pfizer-BioNTech vaccine administered approximately 5 months after the second dose.
- The development of autoantibodies post-second and post-booster doses of the COVID-19 mRNA vaccines.
- Conditions
- Systemic Allergic Reaction
- Being tested
- Pfizer-BioNTech COVID-19 Vaccine (Comirnaty), Placebo, Pfizer-BioNTech COVID-19 Vaccine, Bivalent
- Keywords
- polyethylene glycol (PEG), Pfizer-BioNTech COVID-19 vaccine, Moderna Covid-19 vaccine, Consortium for Food Allergy Research (CoFAR), SARS-CoV-2, Comirnaty
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pfizer-BioNTech COVID-19 Vaccine (Comirnaty)Biological
mRNA vaccine for the prevention of COVID-19. Single dose (0.3mL) via IM.
PlaceboOther
Commercially available sterile, preservative-free 0.9% Sodium Chloride Injection, USP. Volume to match active vaccine controlling for and delivered as a single dose via IM.
Pfizer-BioNTech COVID-19 Vaccine, BivalentBiological
mRNA vaccine booster bivalent (Original and Omicron BA.4/BA.5) for the prevention of COVID-19. Single dose (0.3mL) via IM.
| Study group | Role | What they receive |
|---|---|---|
| Blinded Active Vaccine 2 | Active comparator | Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the active mRNA COVID-19 vaccine (0.3mL) intramuscularly followed by a wash out period of 24 hours then crossover to receive placebo (0.3 mL normal saline) intramuscularly. Receives: Biological: Pfizer-BioNTech COVID-19 Vaccine (Comirnaty); Other: Placebo |
| Blinded Placebo | Placebo comparator | Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the placebo (0.3 mL normal saline) intramuscularly followed by a wash out period of 24 hours then crossover to receive the active mRNA COVID-19 vaccine (0.3mL) intramuscularly. Receives: Biological: Pfizer-BioNTech COVID-19 Vaccine (Comirnaty); Other: Placebo |
| Open-Label Booster Vaccine | Experimental | Participants who did not suffer from a COFAR grade 3 or higher reaction after blinded active vaccine 2 were offered to receive booster dose of the active mRNA COVID-19 vaccine (0.3 mL) intramuscularly 5 months later. Receives: Biological: Pfizer-BioNTech COVID-19 Vaccine (Comirnaty); Biological: Pfizer-BioNTech COVID-19 Vaccine, Bivalent |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Participants Who Had Recurrent Systemic Allergic Reaction to Vaccine
Proportion of participants who had recurrent systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death.
Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels.
Measured: Within the 3-hour post-vaccine observation period
Proportion of Participants Who Had Recurrent Systemic Allergic Reaction to Vaccine
Proportion of participants who had recurrent systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where
Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death.
Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels.
Measured: Within the 3-hour post-vaccine observation period
Secondary outcomes (9)
Proportion of Participants Who Developed Severe Systemic Allergic Reaction to Vaccine
Proportion of participants who developed severe systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where
Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death.
Severe systemic allergic reaction was defined as CoFAR Grade ≥ 3 reaction, regardless of tryptase levels.
Measured: Within the 3-hour post-vaccine observation period
Proportion of Participants Who Developed Mild or Moderate Systemic Allergic Reaction Following Active Vaccine Dose
Proportion of participants who developed mild or moderate systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where
Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death
Mild to moderate systemic allergic reaction was defined as CoFAR Grade 1 or 2 regardless of tryptase level.
Measured: Within the 3-hour post-vaccine observation period
Proportion of Participants Who Developed Mild or Moderate Systemic Allergic Reaction Following Active Vaccine Dose
Proportion of participants who had recurrent systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); grade 2 (moderate) = mild symptoms involving =2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to tr
Measured: Within the 3-hour post-vaccine observation period
Proportion of Participants Who Developed Anaphylactic Reaction Following Active Dose Delivered
Proportion of participants with anaphylactic reactions (Levels 1-3) per Brighton Collaboration Criteria to the COVID-19 vaccine after previously demonstrating a systemic allergic reaction to their first full dose of the COVID-19 vaccine. Anaphylaxis was defined using the Brighton Collaboration Criteria as a clinical syndrome characterized by a sudden onset and rapid progression of signs and symptoms involving ≥2 organ systems including skin, cardiovascular, respiratory, gastrointestinal or tryptase elevation (>upper normal limit). Only specific clinical features from these organ systems meet major and/or minor criteria to provide level of diagnostic certainty for anaphylactic reaction. Reaction meeting levels 1-3 diagnostic certainty are consistent with anaphylaxis
Measured: Within the 3-hour post-vaccine observation period
Proportion of Participants Who Developed Anaphylactic Reaction Following Active Vaccine Dose
Proportion of participants with anaphylactic reactions (Levels 1-3) per Brighton Collaboration Criteria to the COVID-19 vaccine after previously demonstrating a systemic allergic reaction to their first full dose of the COVID-19 vaccine. Anaphylaxis was defined using the Brighton Collaboration Criteria as a clinical syndrome characterized by a sudden onset and rapid progression of signs and symptoms involving ≥2 organ systems including skin, cardiovascular, respiratory, gastrointestinal or tryptase elevation (>upper normal limit). Only specific clinical features from these organ systems meet major and/or minor criteria to provide level of diagnostic certainty for anaphylactic reaction. Reaction meeting levels 1-3 diagnostic certainty are consistent with anaphylaxis.
Measured: Within the 3-hour post-vaccine observation period
Proportion of Participants Who Had Recurrent Systemic Allergic Reaction Following Active Vaccine Dose Compared With Rate of Reaction in Placebo
Participants with recurrent systemic allergic reaction following active vaccine dose in this study compared with reaction in placebo. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild)= mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate)= mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4= severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5= death Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase level. Outcome was calculated as risk difference estimation.
Measured: Within the 3-hour post-vaccine observation period
Proportion of Participants With Less Severe Allergic Reaction to the Vaccine Dose Delivered in This Study Than Recorded Reaction to the First Full COVID-19 Vaccine Dose
Proportion of participants with less severe allergic reaction to the vaccine dose in this study than recorded reaction to the first full COVID-19 vaccine dose (pre-study). Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where
Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death.
Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels.
Measured: Within the 3-hour post-vaccine observation period
Proportion of Participants With More Severe Systemic Allergic Reaction to the Vaccine Dose Delivered in This Study Than Recorded Reaction to the First Full Vaccine Dose
"Proportion of participants with more severe allergic reaction to the vaccine dose in this study than recorded reaction to the first full COVID-19 vaccine dose (pre-study). Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where
Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death
Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels.
Measured: Within the 3-hour post-vaccine observation period
Proportion of Participants With More Severe Systemic Allergic Reaction to the Vaccine Dose Delivered in This Study Than Recorded Reaction to the First Full Vaccine Dose
"Proportion of participants with more severe allergic reaction to the vaccine dose in this study than recorded reaction to the first full COVID-19 vaccine dose (pre-study). Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where
Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death.
Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels.
Measured: Within the 3-hour post-vaccine observation period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2021
- Study start8 Sep 2021
- Primary completion17 Jun 2022
- Study completion22 Feb 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 (1)Papers the sponsor has linked to this study.
- Other trials for Systemic Allergic ReactionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Pamela A Guerrerio, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04977479
- Sponsor's protocol ID
- 10000460
- Other IDs
- 000460-I
- Status last verified
- Jan 2023
- First submitted
- 24 Jul 2021
- Last updated
- 16 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kee SA, Olivera A, Chatman L, Khalid MB, Li MJ, Chu E, Zektser E, Laky K, Frischmeyer-Guerrerio PA. Basophil activation test to BNT162b2 lacks specificity for predicting allergic reactions to the mRNA vaccine. J Allergy Clin Immunol Glob. 2025 May 13;4(3):100495. doi: 10.1016/j.jacig.2025.100495. eCollection 2025 Aug.
PubMed 40497015
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-controlled Crossover Study to Assess the Safety of Administering a Second Dose of a COVID-19 mRNA Vaccine in Individuals Who Experienced a Systemic Allergic Reaction to an Initial Dose
- ClinicalTrials.gov ID
- NCT04977479
- Acronym / sponsor ID
- 10000460
- Conditions
- Systemic Allergic Reaction
- Keywords
- polyethylene glycol (PEG), Pfizer-BioNTech COVID-19 vaccine, Moderna Covid-19 vaccine, Consortium for Food Allergy Research (CoFAR), SARS-CoV-2, Comirnaty
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 8 Sep 2021 (actual)
- Primary completion
- 17 Jun 2022 (actual)
- Study completion
- 22 Feb 2023 (actual)
- First posted
- 27 Jul 2021 (actual)
- Results
- Posted 16 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Some people have allergic reactions to COVID-19 mRNA vaccines. Researchers want to learn more about these reactions to provide guidance on who can safely receive the vaccines, including a second dose in people who had a reaction to the first.
Objective:
To study the safety of giving a second mRNA COVID-19 vaccine dose to people who had a systemic allergic reaction to their first dose.
Eligibility:
People aged 16-69 who had a systemic allergic reaction to their first dose of COVID-19 vaccine.
Design:
Individuals who have underlying health issues may need to come to the NIH for screening tests to make sure they are safe to receive the vaccine. People who are eligible to participate in the study will be admitted to the NIH hospital and stay for at least 4 days. They will give urine samples. They will have a nasal swab SARS-CoV-2 test. They will have an intravenous line placed in each arm. They will get the study vaccine (Pfizer-BioNTech COVID-19 vaccine) and one dose of placebo on different days. They will have breathing tests. They may have clinical photography if they develop a rash.
Participants will have 4 follow-up visits - 2 by phone and 2 in-person visits at the NIH campus . They will have allergy skin testing at one visit. Drops of different allergens or controls will be placed on their back or arm. The skin under each drop will be scratched with a tool. If the results are negative, a small amount of allergen will be injected just below the surface of their skin. Participants who have no or only a mild allergic reaction to the second dose of the vaccine may be eligible to receive a Booster dose at the NIH.
Participation will last for approximately 5 months.
Detailed description
Study Description:
This is a single-site study to determine the safety of administering a dose of the Pfizer-BioNTech mRNA coronavirus disease 2019 (COVID-19) vaccine (Comirnaty) to individuals who experienced a systemic allergic reaction to their first full dose of the same vaccine or the Moderna mRNA vaccine, and to investigate possible mechanisms underlying allergic reactions.
Objectives:
Primary Objective:
- Assess the proportion of participants who develop a systemic allergic reaction (Consortium for Food Allergy Research grade 2 reaction and above regardless of tryptase, or CoFAR grade 1 with elevated tryptase [1.2 X baseline plus 2ng/mL]) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine.
Secondary Objectives:
- Assess the proportion of participants who develop a severe systemic allergic reaction (CoFAR Grade 3 reaction or higher regardless of tryptase) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine.
- Assess the proportion of participants who develop a mild-moderate allergic reaction (CoFAR Grade 1 or 2 reaction regardless of tryptase) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine.
- Assess the proportion of participants with anaphylactic reactions (Levels 1-3) per Brighton Collaboration Criteria (see Appendix B) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine.
- Assess the proportion of participants who develop a systemic allergic reaction (CoFAR Grade 2 reaction or higher regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine compared to the rate of these reactions following placebo administration.
- Compare the severity of allergic reactions to the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine to the severity of the reaction following administration of a subsequent dose of the Pfizer-BioNTech vaccine in individuals who experienced a systemic allergic reaction (CoFAR grade 2 reaction and above regardless of tryptase, or CoFAR grade 1 with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine.
Exploratory Objectives:
- Assess the risk of having a systemic allergic reaction to a dose of the Pfizer-BioNTech COVID-19 vaccine in participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the same vaccine or the Moderna COVID-19 according to baseline covariates.
- Examine possible mechanisms of allergic reactions to mRNA-based COVID-19 vaccines.
- Assess innate and adaptive immune responses, including functional antibody levels, to the Pfizer-BioNTech COVID-19 vaccine
- Investigate mental health characteristics of participants who experience an allergic reaction to the COVID-19 vaccine.
- Assess psychological impact of allergic reactions to the COVID-19 vaccine and examine changes in stress levels over time.
- Assess anxiety levels in participants and examine changes in anxiety over time.
- Assess the proportion of participants who experience no reaction or only a mild reaction (CoFAR Grade 2 or below) to a booster dose of the Pfizer-BioNTech vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2 ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine and no allergic reaction or a mild reaction (CoFAR Grade 2 or below) to a subsequent (second) dose of the Pfizer-BioNTech vaccine.
- Assess the development of autoantibodies after COVID-19 vaccination.
Endpoints:<TAB>
Primary Endpoint:
- The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who experience a systemic allergic reaction (CoFAR Grade 2 and above reaction regardless of tryptase, or CoFAR grade 1 with elevated tryptase [1.2 X baseline plus 2ng/mL]) within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine.
Secondary Endpoints:
- The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who experience a severe systemic allergic reaction (CoFAR grade 3 reaction and above) within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine.
- The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who experience a mild-moderate allergic reaction (CoFAR grade 1 or 2 reaction regardless of tryptase) within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine.
- The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who experience an anaphylactic reaction (Levels 1-3) per Brighton Collaboration Criteria within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine.
- The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who experience a systemic allergic reaction (CoFAR grade 2 reaction and above regardless of tryptase, or CoFAR grade 1 with elevated tryptase [1.2 X baseline plus 2ng/mL]) within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine compared to the rate of these reactions following placebo administration.
- The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who develop a lower or higher grade allergic reaction within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine.
Exploratory Endpoints:
- Prevalence of polyethylene glycol (PEG) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in each participant at baseline.
- Changes in anti-PEG and SARS-CoV-2 antibodies in each participant approximately 1 and 5 months after receiving the dose of the Pfizer-BioNTech vaccine administered on study.
- Prevalence of positive skin testing to the vaccine and/or vaccine components including PEG- and polysorbate 80-containing medications.
- Changes in biomarkers from baseline to post-dose of the Pfizer-BioNTech vaccine administered on study (e.g., known mediators of systemic reactions due to mast cell activation, markers of inflammatory response, markers of basophil and neutrophil activation, markers associated with activation of the classical and alternative complement pathways or kinin system, proteomics, metabolomics).
- Changes in blood transcriptomics after vaccination.
- Changes in innate and adaptive immune responses including functional antibody levels after vaccination.
- Mental health/anxiety questionnaire scores and anxiety level ratings at baseline.
- Results of psychiatric consultation/mental health interview.
- Changes in mental health/anxiety questionnaire scores and anxiety level ratings over the study period.
- The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2 ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine and no allergic reaction or a mild reaction (CoFAR Grade 2 or below) to a subsequent (second) dose of the Pfizer-BioNTech vaccine who experience no reaction or only a mild reaction (CoFAR Grade 2 or below) to a booster dose of the Pfizer-BioNTech vaccine administered approximately 5 months after the second dose.
- Changes in blood transcriptomics after vaccination.
- Changes in innate and adaptive immune responses including functional antibody levels after vaccination.
- Mental health/anxiety questionnaire scores and anxiety level ratings at baseline.
- Results of psychiatric consultation/mental health interview.
- Changes in mental health/anxiety questionnaire scores and anxiety level ratings over the study period.
- The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2 ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine and no allergic reaction or a mild reaction (CoFAR Grade 2 or below) to a subsequent (second) dose of the Pfizer-BioNTech vaccine who experience no reaction or only a mild reaction (CoFAR Grade 2 or below) to a booster dose of the Pfizer-BioNTech vaccine administered approximately 5 months after the second dose.
- The development of autoantibodies post-second and post-booster doses of the COVID-19 mRNA vaccines.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Blinded Active Vaccine 2 | Active comparator | Biological: Pfizer-BioNTech COVID-19 Vaccine (Comirnaty), Other: PlaceboParticipants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the active mRNA COVID-19 vaccine (0.3mL) intramuscularly followed by a wash out period of 24 hours then crossover to receive placebo (0.3 mL normal saline) intramuscularly. |
| Blinded Placebo | Placebo comparator | Biological: Pfizer-BioNTech COVID-19 Vaccine (Comirnaty), Other: PlaceboParticipants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the placebo (0.3 mL normal saline) intramuscularly followed by a wash out period of 24 hours then crossover to receive the active mRNA COVID-19 vaccine (0.3mL) intramuscularly. |
| Open-Label Booster Vaccine | Experimental | Biological: Pfizer-BioNTech COVID-19 Vaccine (Comirnaty), Biological: Pfizer-BioNTech COVID-19 Vaccine, BivalentParticipants who did not suffer from a COFAR grade 3 or higher reaction after blinded active vaccine 2 were offered to receive booster dose of the active mRNA COVID-19 vaccine (0.3 mL) intramuscularly 5 months later. |
Who may qualify
- Ages
- 16 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Ability to provide informed consent.
- Stated willingness to comply with all study procedures (including discontinuing medications as needed and availability for the duration of the study.
- Aged 16-69 years.
- Must have experienced a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2 ng/mL] per modified CoFAR Grading Scale for Systemic Allergic Reactions Version 3.0) to the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine. Patients without documented hypoxia, hypotension, or evidence of end-organ damage who were treated with epinephrine infusion would be considered as CoFAR Grade 3 reaction and may be eligible per investigator discretion.
Key exclusion criteria (17 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Experienced a Grade 4 systemic allergic reaction (per CoFAR Grading Scale for Systemic Allergic Reactions Version 3.0) to the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine.
- Known exposure to SARS-CoV-2 and still within the quarantine window.
- Symptoms consistent with acute COVID-19 infection or known COVID-19 infection (positive reverse transcription-polymerase chain reaction [RT-PCR] or antigen test) and still within the quarantine window
- Have an acute illness, including body temperature greater than 100.4 degrees F, within 14 days prior to enrollment.
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 |
|---|---|---|
| Pfizer-BioNTech COVID-19 Vaccine (Comirnaty)mRNA vaccine for the prevention of COVID-19. Single dose (0.3mL) via IM. | Biological | Blinded Active Vaccine 2, Blinded Placebo, Open-Label Booster Vaccine |
| PlaceboCommercially available sterile, preservative-free 0.9% Sodium Chloride Injection, USP. Volume to match active vaccine controlling for and delivered as a single dose via IM. | Other | Blinded Active Vaccine 2, Blinded Placebo |
| Pfizer-BioNTech COVID-19 Vaccine, BivalentmRNA vaccine booster bivalent (Original and Omicron BA.4/BA.5) for the prevention of COVID-19. Single dose (0.3mL) via IM. | Biological | Open-Label Booster Vaccine |
Primary outcome
Proportion of Participants Who Had Recurrent Systemic Allergic Reaction to Vaccine
Time frame: Within the 3-hour post-vaccine observation period
Proportion of participants who had recurrent systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death. Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels.
Proportion of Participants Who Had Recurrent Systemic Allergic Reaction to Vaccine
Time frame: Within the 3-hour post-vaccine observation period
Proportion of participants who had recurrent systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death. Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels.
9 secondary outcomes
Proportion of Participants Who Developed Severe Systemic Allergic Reaction to Vaccine
Time frame: Within the 3-hour post-vaccine observation period
Proportion of Participants Who Developed Mild or Moderate Systemic Allergic Reaction Following Active Vaccine Dose
Time frame: Within the 3-hour post-vaccine observation period
Proportion of Participants Who Developed Mild or Moderate Systemic Allergic Reaction Following Active Vaccine Dose
Time frame: Within the 3-hour post-vaccine observation period
Proportion of Participants Who Developed Anaphylactic Reaction Following Active Dose Delivered
Time frame: Within the 3-hour post-vaccine observation period
Proportion of Participants Who Developed Anaphylactic Reaction Following Active Vaccine Dose
Time frame: Within the 3-hour post-vaccine observation period
Proportion of Participants Who Had Recurrent Systemic Allergic Reaction Following Active Vaccine Dose Compared With Rate of Reaction in Placebo
Time frame: Within the 3-hour post-vaccine observation period
Proportion of Participants With Less Severe Allergic Reaction to the Vaccine Dose Delivered in This Study Than Recorded Reaction to the First Full COVID-19 Vaccine Dose
Time frame: Within the 3-hour post-vaccine observation period
Proportion of Participants With More Severe Systemic Allergic Reaction to the Vaccine Dose Delivered in This Study Than Recorded Reaction to the First Full Vaccine Dose
Time frame: Within the 3-hour post-vaccine observation period
Proportion of Participants With More Severe Systemic Allergic Reaction to the Vaccine Dose Delivered in This Study Than Recorded Reaction to the First Full Vaccine Dose
Time frame: Within the 3-hour post-vaccine observation period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40497015Kee SA, Olivera A, Chatman L, Khalid MB, Li MJ, Chu E, Zektser E, Laky K, Frischmeyer-Guerrerio PA. Basophil activation test to BNT162b2 lacks specificity for predicting allergic reactions to the mRNA vaccine. J Allergy Clin Immunol Glob. 2025 May 13;4(3):100495. doi: 10.1016/j.jacig.2025.100495. eCollection 2025 Aug.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pamela A Guerrerio, M.D. principal investigator
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1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pfizer-BioNTech COVID-19 Vaccine (Comirnaty) and Pfizer-BioNTech COVID-19 Vaccine, Bivalent in people with Systemic Allergic Reaction, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site 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 7 inclusion and 17 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 16 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 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 16 Oct 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 Had Recurrent Systemic Allergic Reaction to Vaccine (time frame: Within the 3-hour post-vaccine observation period). 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 NCT04977479, which also lists 1 linked publication.
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 16 Oct 2023.