Purpose

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 compared to a non-atopic population.

Conditions

Eligibility

Eligible Ages
Between 18 Years and 69 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 Non-Atopic Group): 1. Able to understand and provide informed consent 2. Male or non-pregnant female 18 to 69 years of age, inclusive, on the date of first study vaccination/placebo administration 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, or insect venom(s) with use of epinephrine within the last 5 years 2. History of documented, immediate allergic reactions to 2 or more unrelated drugs within the last 5 years 3. A convincing clinical history, or a history that is accompanied by a positive skin test, of an immediate reaction to a drug or vaccine within the last 5 years 4. History of a physician-diagnosed mast cell disorder (e.g., mastocytosis, mast cell activation syndrome, or hereditary alpha-tryptasemia). Mast cell activation syndrome must meet consensus criteria. Non-Atopic Group: Individuals who meet all of the following criteria are eligible for enrollment in the non-atopic group: 1. No history of allergic disorders, including allergic asthma, rhinitis, conjunctivitis, atopic dermatitis, chronic spontaneous urticaria, or angioedema 2. No history of allergic reactions to foods or insect venoms 3. No history of allergic reactions to drugs or vaccines 4. No history of a mast cell disorder (e.g., mastocytosis, mast cell activation syndrome, 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 to give written informed consent or comply with study protocol 2. 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 3. History of a severe reaction to any component of the Pfizer-BioNTech COVID-19 Vaccine or Moderna COVID-19 Vaccine 4. History of contact dermatitis with confirmed patch test reaction to Prevalence of polyethylene glycol (PEG) 5. History of reaction to Doxil® 6. Known exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and still within the quarantine window 7. 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 8. Have an acute illness, including body temperature greater than 100.4 degrees, within 14 days of the first study vaccination/placebo administration or 3 days prior to each subsequent vaccination 9. History of autoimmune or other disorders requiring systemic immune modulators 10. History of acute urticaria within 28 days of randomization 11. Pregnant 12. Have received any vaccines within 14 days of the first study vaccination/placebo administration or plan to receive other vaccines during the study period 13. Had any allergen immunotherapy administration within 24 hours prior to vaccination/placebo administration or plan to receive within 24 hours after vaccination/placebo administration 14. Have received a biologic therapy within 6 months of randomization 15. Use of systemic steroids for any reason within 28 days of randomization 16. Use of Zileuton® within 14 days of randomization 17. Use of Emergency Use Authorization (EUA) monoclonal antibodies casirivimab and imdevimab, or bamlanivimab, or any other antibody agent for treatment or prevention of COVID-19 within 3 months of randomization 18. 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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
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.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Moderna COVID-19 Vaccine
The Moderna COVID-19 Vaccine (0.5 mL) will be administered intramuscularly in the deltoid, as a series of two doses (0.5 mL each) administered 1 month (28 days) apart.
  • Biological: Moderna COVID-19 Vaccine
    Intramuscular injection
    Other names:
    • mRNA-1273
Experimental
Pfizer-BioNTech COVID-19 Vaccine
The Pfizer-BioNTech COVID-19 Vaccine (0.3 mL) will be administered intramuscularly in the deltoid, as a series of two doses (0.3 mL each) administered 3 weeks (21 days) apart.
  • Biological: Pfizer-BioNTech COVID-19 Vaccine
    Intramuscular injection
    Other names:
    • BNT162b2
Experimental
Placebo +Moderna COVID-19 Vaccine
Participants will receive placebo as a first dose followed by two doses of their assigned active vaccine at subsequent visits. 0.5 mL of placebo will be administered intramuscularly in the deltoid. The placebo dose will be followed by two doses of Moderna COVID-19 Vaccine, with the first dose administered 1 month later. The Moderna COVID-19 Vaccine (0.5 mL) will be administered intramuscularly in the deltoid, as a series of two doses (0.5 mL each) administered 1 month (28 days) apart.
  • Biological: Moderna COVID-19 Vaccine
    Intramuscular injection
    Other names:
    • mRNA-1273
  • Biological: Placebo
    Intramuscular injection
    Other names:
    • sterile, preservative-free 0.9% Sodium Chloride Injection
Experimental
Placebo+Pfizer-BioNTech COVID-19 Vaccine
Participants will receive placebo as a first dose followed by two doses of their assigned active vaccine at subsequent visits. 0.3 mL of placebo will be administered intramuscularly in the deltoid. The placebo dose will be followed by two doses of Pfizer-BioNTech COVID-19 Vaccine, with the first dose administered 1 month later. The Pfizer-BioNTech COVID-19 Vaccine (0.3 mL) will be administered intramuscularly in the deltoid, as a series of two doses (0.3 mL each) administered 3 weeks (21 days) apart.
  • Biological: Pfizer-BioNTech COVID-19 Vaccine
    Intramuscular injection
    Other names:
    • BNT162b2
  • Biological: Placebo
    Intramuscular injection
    Other names:
    • sterile, preservative-free 0.9% Sodium Chloride Injection

Recruiting Locations

More Details

NCT ID
NCT04761822
Status
Not yet recruiting
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Detailed Description

This is a multicenter, randomized, initially blinded (masked), phase 2 trial to assess SARS-CoV-2 vaccination reactions in two populations: - One population including individuals with a history of allergic reactions or Mast Cell Disorder (HA/MCD),and - One non-atopic population. Approximately 2040 HA/MCD and 1360 non-atopic participants will be enrolled across participating sites in the United States. Approximately two-thirds of participants enrolled in each of the 2 groups will be female. This is because the vast majority of cases of anaphylaxis to the COVID-19 vaccines have occurred in women. Enrollment of participants who qualify only on the basis of reactions to multiple unrelated drugs will be limited to approximately 300. Enrollment of the MCD group is anticipated to be at least 200 participants, and not more than 300 participants. Participants in each population will be randomized 2:2:1:1 to receive the Pfizer-BioNTech COVID-19 Vaccine, Moderna COVID-19 Vaccine, placebo + Pfizer-BioNTech COVID-19 Vaccine, or placebo + Moderna COVID-19 Vaccine. Participants randomized to one of the placebo groups will receive placebo as a first dose and will receive two doses of their assigned active vaccine at subsequent visits. During the first visit, all participants will be initially-blinded to whether they are receiving placebo or vaccine, and to which vaccine they are receiving. 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 the study participant which vaccine has been assigned, once the second injection visit is scheduled. However, the blind over placebo versus vaccine will remain in effect until after the second visit. During a follow-up call, scheduled 3 days after the second injection, participants will be unblinded as to whether they received placebo or active vaccine. Study Duration: Randomized and vaccinated participants will complete study participation in approximately 29 days if vaccinated with the Pfizer-BioNTech COVID-19 Vaccine, 36 days if vaccinated with the Moderna COVID-19 Vaccine, and 50 or 64 days if administered placebo before receiving two doses of either the Pfizer-BioNTech COVID-19 Vaccine or the Moderna COVID-19 Vaccine, respectively. Total study duration: Approximately 17 weeks.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.