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
Condition: Systemic Allergic Reaction
MeSH terms: COVID-19; Hypersensitivity
Intervention: Pfizer-BioNTech COVID-19 Vaccine (Comirnaty); Placebo; Pfizer-BioNTech COVID-19 Vaccine, Bivalent
Intervention description: mRNA vaccine for the prevention of COVID-19. Single dose (0.3mL) via IM.; 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.; mRNA vaccine booster bivalent (Original and Omicron BA.4/BA.5) for the prevention of COVID-19. Single dose (0.3mL) via IM.
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Minimum age: 16 Years
Maximum age: 69 Years
Healthy volunteers: No
Keywords: polyethylene glycol (PEG); Pfizer-BioNTech COVID-19 vaccine; Moderna Covid-19 vaccine; Consortium for Food Allergy Research (CoFAR); SARS-CoV-2; Comirnaty

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 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.
    

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 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.

        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.

          -  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.