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Protocol Details

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

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 16 Years
Max Age: 69 Years

Referral Letter Required


Population Exclusion(s)



polyethylene glycol (PEG);
Pfizer-BioNTech COVID-19 vaccine;
Moderna Covid-19 vaccine;
Consortium for Food Allergy Research (CoFAR);

Recruitment Keyword(s)



systemic allergic reaction

Investigational Drug(s)

Pfizer-BioNTech COVID-19 Vaccine (comirnaty)
Pfizer-BioNTech COVID-19 Vaccine, Bivalent

Investigational Device(s)



Biological/Vaccine: Pfizer-BioNTech COVID-19 Vaccine, Bivalent
Other: Placebo
Biological/Vaccine: Pfizer-BioNTech COVID-19 Vaccine (Comirnaty)

Supporting Site

National Institute of Allergy and Infectious Diseases


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.


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.


People aged 16-69 who had a systemic allergic reaction to their first dose of COVID-19 vaccine.


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.

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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.


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.

-Are moderately or severely immunocompromised.

-History of acute urticaria within 28 days prior to enrollment.


-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.

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Pamela A. Guerrerio, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
BG 10 RM 11N240B
(301) 402-9782

Ellen Zektser, R.N.
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health
Building 10
Room 6D44
10 Center Drive
Bethesda, Maryland 20892
(301) 761-7565

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

Clinical Trials Number:


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