COVID19 SARS Vaccinations: Systemic Allergic Reactions to SARS-CoV-2 Vaccinations
Condition: SARS-CoV Infection; COVID-19; Allergic Reaction; Mast Cell Disorder
MeSH terms: COVID-19; Severe Acute Respiratory Syndrome; Hypersensitivity
Intervention: Moderna COVID-19 Vaccine; Pfizer-BioNTech COVID-19 Vaccine; Placebo
Intervention description: Intramuscular injection; Intramuscular injection; Intramuscular injection
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking description: Due to the different dosing schedules for the Pfizer-BioNTech COVID-19 Vaccine and Moderna COVID-19 Vaccine, it will become apparent to both the site staff and study participant which vaccine has been assigned, once their second injection is scheduled. Participants and the staff will be unblinded (unmasked) during the follow-up call 3 days after the second injection when a third appointment (for those who received a placebo injection first) is, or is not (active vaccinations only) scheduled.
Enrollment: 746.0
Sex: All
Minimum age: 5 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: SARS-CoV-2 vaccination; COVID-19 vaccination; Systemic Allergic Reactions to SARS-CoV-2 vaccination

Summary:

      Background: Allergic reactions have been reported to occur after vaccination with both the
      Pfizer-BioNTech COVID-19 Vaccine and Moderna COVID-19 Vaccine. Allergic reactions range from
      mild to severe and include life- threatening anaphylactic reactions, although no deaths have
      been reported with either vaccine.

      This study is designed with two principal aims:

        -  To estimate the proportions of systemic allergic reactions to the Pfizer-BioNTech
           COVID-19 Vaccine and the Moderna COVID-19 Vaccine in a High-Allergy/Mast Cell Disorder
           (HA/MCD) population, and

        -  If the risk in the HA/MCD is demonstrable, to determine whether the proportions are
           higher in the HA/MCD in comparison to a representative population without severe
           allergies or mast cell disorders
    

Eligibility criteria:

        Inclusion Criteria:

        Individuals who meet all of the following criteria are eligible for enrollment as study
        participants:

        Both groups (e.g., High-Allergy and Mast Cell Disorder (HA/MCD) Group and Comparison
        Group):

          1. Able to understand and provide informed consent

          2. Male or non-pregnant female ≥12 years of age on the date of first study
             vaccination/placebo administration (protocol versions 1.0 - 4.0) OR male or
             non-pregnant female 5-17 years of age on the date of first study vaccination/placebo
             administration (protocol version 5.0)

          3. Females of childbearing potential must have a negative pregnancy test prior to the
             first vaccination and placebo administration, if applicable.

             --If a participant becomes pregnant after receiving a placebo dose but prior to
             receiving study vaccination, she will be discontinued from the study

          4. Females of reproductive potential° and sexually active must agree to use FDA approved
             methods of birth control for the duration of the study. These include hormonal
             contraceptives, intrauterine device, double barrier contraception (i.e., condom plus
             diaphragm), or male partner with documented vasectomy.

               -  Menopause is defined as at least 12 consecutive months without menses; if in
                  question, a follicle stimulating hormone of ≥25 U/mL must be documented.

               -  Hysterectomy, bilateral oophorectomy, or bilateral tubal ligation must be
                  documented, as applicable; if documented, women with these conditions are not
                  required to use additional contraception.

        High-Allergy and Mast Cell Disorder (HA/MCD) Group:

        Individuals who meet at least one of the following criteria are eligible for enrollment in
        the HA/MCD group:

          1. History of a severe allergic reaction to food(s), allergen immunotherapy, insect
             venom(s), or latex with use of epinephrine within the last 15 years

          2. History of an Emergency Department visit with convincing evidence of a systemic
             allergic reaction (consistent with CoFAR Grade 3 or higher) to food(s), allergen
             immunotherapy, insect venom(s), or latex within the last 15 years

          3. History of documented, immediate allergic reactions to 2 or more unrelated drugs
             within the last 15 years

          4. A convincing clinical history, or a history that is accompanied by a positive skin
             test, of an immediate reaction to a drug, vaccine, or latex within the last 15 years

          5. History of physician-diagnosed idiopathic anaphylaxis requiring epinephrine or an
             Emergency Department visit in the last 15 years

          6. History of a physician-diagnosed mast cell disorder (e.g., mastocytosis, mast cell
             activation syndrome [MCAS], or hereditary alpha-tryptasemia). MCAS must meet consensus
             criteria as defined below:

               -  Criterion A: Typical clinical signs of severe, recurrent (episodic) systemic Mast
                  Cell Activation are present (often in form of anaphylaxis)

                  ---Definition of systemic: involving at least 2 organ systems

               -  Criterion B: Involvement of Mast Cell (MC) is documented by biochemical studies

                  --- Preferred marker: increase in serum tryptase level from the individual's
                  baseline to plus 20% + 2 ng/ml

               -  Criterion C: Response of symptoms to therapy with MC-stabilizing agents, drugs
                  directed against MC mediator production or drugs blocking mediator release or
                  effects of MC-derived mediators

               -  NOTE: All 3 Mast Cell Activation Syndrome (MCAS) criteria (A + B + C) must be
                  fulfilled to call a condition MCAS.

        Comparison Group:

        Individuals who meet all of the following criteria are eligible for enrollment in the
        comparison group:

          1. No history of allergic asthma or atopic dermatitis within the last 10 years

          2. No history of chronic spontaneous urticaria, or angioedema

          3. No history of allergic reactions to foods or insect venoms

          4. No history of allergic reactions to drugs or vaccines

          5. No history of anaphylaxis

          6. No history of a mast cell disorder (e.g., mastocytosis, mast cell activation syndrome
             [MCAS], or hereditary alpha- tryptasemia)

        Exclusion Criteria:

        Individuals who meet any of these criteria are not eligible for enrollment as study
        participants:

          1. Inability or unwillingness of a participant and/or parent/legal guardian to give
             written informed consent and/or assent, as applicable, or to comply with study
             protocol

          2. Weight less than 15 kg (33 lbs)

          3. Prior receipt of any doses of the Pfizer-BioNTech coronavirus disease 2019 (COVID-19)
             Vaccine, Moderna COVID-19 Vaccine, or any other COVID-19 vaccine

          4. History of a severe reaction to any component of the Pfizer-BioNTech COVID-19 Vaccine
             or Moderna COVID-19 Vaccine

          5. History of contact dermatitis with confirmed patch test reaction to Prevalence of
             polyethylene glycol (PEG)

          6. History of reaction to Doxil®

          7. Known exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and
             still within the quarantine window

          8. Symptoms consistent with acute COVID-19 infection or known COVID-19 infection
             (positive Polymerase chain reaction [PCR] or antigen test) and still within the
             quarantine window

          9. Have an acute illness, including body temperature greater than 100.4 degrees
             Fahrenheit, within 14 days of the first study vaccination/placebo administration or 3
             days prior to each subsequent vaccination

         10. History of autoimmune or other disorders requiring systemic immune modulators

         11. History of acute urticaria within 28 days of randomization

         12. Pregnant

         13. Have received any vaccines within 14 days of the first study vaccination/placebo
             administration or plan to receive other vaccines during the study period

         14. Had any allergen immunotherapy administration within 24 hours prior to
             vaccination/placebo administration or plan to receive within 24 hours after
             vaccination/placebo administration

         15. Have received a biologic therapy within 6 months of randomization

         16. Use of systemic steroids for any reason within 28 days of randomization

         17. Use of Zileuton® within 14 days of randomization

         18. Use of any monoclonal antibody agent for treatment or prevention of COVID-19 within 3
             months of randomization

         19. Coronary artery disease, peripheral or cerebral vascular disease, unstable angina, or
             cardiac arrhythmia, other than supraventricular tachycardia (SVT)

         20. Medically unstable hypertension

         21. Current use of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors,
             monoamine oxidase (MAO) inhibitors, tricyclic anti-depressants or other agents that
             could interfere with the treatment of anaphylaxis, in the opinion of the investigator

         22. Unstable asthma within 3 months of randomization or symptomatic asthma on the day of
             vaccination, as assessed by the site investigator

         23. Have past or current medical problems or findings from physical exam or laboratory
             testing not listed above, which in the opinion of the investigator, may pose
             additional risks from participation in the study or which may interfere with the
             ability to comply with study requirements --This includes individuals with underlying
             conditions or other medications that, in the opinion of the investigator, may increase
             risk in the event of an anaphylactic reaction or lead to complications following
             administration of epinephrine