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
Brief 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. 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 18-69 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 a urine sample. 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 3 follow-up visits . 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. Participation will last for 6 months .

Detailed Description

Widespread vaccination will be essential to overcome the public health crisis created by

COVID-19. Although rare, the allergic reactions that have occurred because of COVID-19 mRNA

vaccinations have created substantial fear and anxiety in the general population where

allergic disease is common. This concern may translate to reduced willingness for patients

with a history of severe allergies to receive the COVID-19 vaccine, and/or a hesitancy on the

part of physicians to administer the vaccine to these patients out of concern that the

vaccine will trigger an allergic reaction. Furthermore, the high rate of suspected allergic

reactions following the initial doses of these vaccines may prevent a substantial fraction of

the population from receiving a second dose, which may be necessary for the vaccine to be

fully effective. Currently, the safety of administering a second dose of these vaccines to

patients who experienced an allergic reaction to the first dose is unknown. For these

reasons, a better understanding of the mechanisms responsible for allergic reactions to the

mRNA COVID vaccines is critically needed in order to reassure the public and to provide

evidence-based guidance on who can safely receive these vaccines, including a second dose in

those individuals who experienced a reaction to the first dose.



The study population will consist of individuals 18-69 years of age who experienced a

systemic allergic reaction after receiving the first dose of the Pfizer-BioNTech or Moderna

COVID-19 vaccine. Eligible individuals will be enrolled and receive a dose of the

Pfizer-BioNTech vaccine as well as placebo in a blinded, randomized order on consecutive

days. To maximize safety, all participants will be admitted to a 4-day inpatient stay in the

Intensive Care Unit at the NIH Clinical Center where experienced staff and all equipment and

medications necessary to treat severe allergic reactions are readily available. Two IV lines

will be inserted prior to study vaccination to allow for frequent blood draws and rapid

administration of fluids/medications if needed in the event of a reaction. There will be a

remote follow-up one week after discharge. Participants will return to the NIH approximately

9 weeks and then 6 months after discharge to provide additional research samples. At the

9-week visit, participants will undergo allergy skin testing to investigate the potential

role of IgE in triggering allergic reactions to the vaccine.

Recruiting
Systemic Allergic Reaction

Biological: Pfizer-BioNTech COVID-19 Vaccine
mRNA vaccine for the prevention of COVID-19 under FDA EUA. Single dose (0.3mL) via IM.
Active Vaccine

Other: Placebo
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.
Placebo

Eligibility Criteria

- INCLUSION CRITERIA:

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 18-69 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 CoFAR Grading Scale for Systemic Allergic Reactions Version 3.0) to the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine. - 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. - Willing to allow storage of blood and other biological samples for future use in medical research.

EXCLUSION CRITERIA:

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. - History of acute urticaria within 28 days prior to enrollment. - Pregnant. - Have received any vaccines within 14 days prior to enrollment. - 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.

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years~Maximum: 69 Years
Countries
United States
Locations

National Institutes of Health Clinical Center
Bethesda, Maryland, 20892

Recruiting

Investigator: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
Contact: 800-411-1222

TTY8664111010 prpl@cc.nih.gov

Contacts

Leah Lewis-Garber
(240) 328-5870
leah.lewis-garber@nih.gov

Pamela A Guerrerio, M.D.
Principal Investigator
National Institute of Allergy and Infectious Diseases (NIAID)

National Institute of Allergy and Infectious Diseases (NIAID)
NCT Number
Keywords
polyethylene glycol (PEG)
Pfizer-BioNTech COVID-19 vaccine
Moderna Covid-19 vaccine
Consortium for Food Allergy Research (CoFAR)
SARS-CoV-2
MeSH Terms
Hypersensitivity