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:
1. 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:
1. 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.
2. 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.
3. 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.
4. 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.
5. 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:
1. 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.
2. Examine possible mechanisms of allergic reactions to mRNA-based COVID-19 vaccines.
3. Assess innate and adaptive immune responses, including functional antibody levels, to
the Pfizer-BioNTech COVID-19 vaccine. 4. Investigate mental health characteristics of participants who experience an allergic
reaction to the COVID-19 vaccine.
5. Assess psychological impact of allergic reactions to the COVID-19 vaccine and examine
changes in stress levels over time.
6. Assess anxiety levels in participants and examine changes in anxiety over time.
7. 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.
8. Assess the development of autoantibodies after COVID-19 vaccination.
Endpoints:
Primary Endpoint:
1. 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:
1. 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.
2. 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.
3. 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.
4. 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.
5. 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:
1. Prevalence of polyethylene glycol (PEG) and severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) antibodies in each participant at baseline.
2. 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.
3. Prevalence of positive skin testing to the vaccine and/or vaccine components including
PEG- and polysorbate 80-containing medications.
4. 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).
5. Changes in blood transcriptomics after vaccination.
6. Changes in innate and adaptive immune responses including functional antibody levels
after vaccination.
7. Mental health/anxiety questionnaire scores and anxiety level ratings at baseline.
8. Results of psychiatric consultation/mental health interview.
9. Changes in mental health/anxiety questionnaire scores and anxiety level ratings over the
study period.
10. 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.
11. Changes in blood transcriptomics after vaccination.
12. Changes in innate and adaptive immune responses including functional antibody levels
after vaccination.
13. Mental health/anxiety questionnaire scores and anxiety level ratings at baseline.
14. Results of psychiatric consultation/mental health interview.
15. Changes in mental health/anxiety questionnaire scores and anxiety level ratings over the
study period.
16. 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.
17. The development of autoantibodies post-second and post-booster doses of the COVID-19
mRNA vaccines.
