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COVID19 SARS Vaccinations: Systemic Allergic Reactions to SARS-CoV-2 Vaccinations (SARS)

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ClinicalTrials.gov Identifier: NCT04761822
Recruitment Status : Recruiting
First Posted : February 21, 2021
Last Update Posted : May 17, 2021
Sponsor:
Collaborators:
Immune Tolerance Network (ITN)
Rho Federal Systems Division, Inc.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE February 17, 2021
First Posted Date  ICMJE February 21, 2021
Last Update Posted Date May 17, 2021
Actual Study Start Date  ICMJE April 7, 2021
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 17, 2021)
  • Proportion of participants who experience a systemic allergic reaction to either dose of the Pfizer-BioNTech COVID-19 Vaccine [ Time Frame: Within the 90-minute post- vaccination observation period ]
    Symptoms considered to be allergic will be graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Note- It is possible for a participant to have a reaction to:
    • Either dose 1 or dose 2 of the assigned COVID-19 vaccine, but not to both doses, since a participant who has a reaction meeting qualifying criteria to dose 1 will not be eligible to receive the second dose; or,
    • Neither dose of the assigned COVID-19 vaccine.
  • Proportion of participants who experience a systemic allergic reaction to either dose of the Moderna COVID-19 Vaccine [ Time Frame: Within the 90-minute post- vaccination observation period ]
    Symptoms considered to be allergic will be graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Note- It is possible for a participant to have a reaction to: Either dose 1 or dose 2 of the assigned COVID-19 vaccine, but not to both doses, since a participant who has a reaction meeting qualifying criteria to dose 1 will not be eligible to receive the second dose; or, Neither dose of the assigned COVID-19 vaccine.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 17, 2021)
  • Proportion of participants who experience a severe (≥ Grade 3) systemic allergic reaction to either dose of each vaccine [ Time Frame: Within the 90-minute post- vaccination observation period ]
    Symptoms considered to be allergic will be graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Note- It is possible for a participant to have a reaction to: Either dose 1 or dose 2 of the assigned COVID-19 vaccine, but not to both doses, since a participant who has a reaction meeting qualifying criteria to dose 1 will not be eligible to receive the second dose; or, Neither dose of the assigned COVID-19 vaccine.
  • Proportion of participants who experience an anaphylactic reaction per Brighton Collaboration Criteria to either dose of each vaccine [ Time Frame: Within the 90-minute post- vaccination observation period ]
    Defined by Levels 1-3 per Brighton Collaboration Criteria. Brighton Collaboration case definition criteria for anaphylaxis. Brighton level 1 represents the highest level of diagnostic certainty that a reported case is a case of anaphylaxis, levels 2 and 3 represent successively lower levels of diagnostic certainty.
  • Proportion of participants who experience a systemic allergic reaction ≥Grade 2 to the first dose [ Time Frame: Within the 90-minute post- vaccination observation period ]
    Symptoms considered to be allergic will be graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale is Grade 1 through 5, the higher the grade, the more severe the allergic reaction.
  • Proportion of participants who experience a systemic allergic reaction ≥Grade 2 to the second dose conditional on no systemic allergic reaction to the first dose [ Time Frame: Within the 90-minute post- vaccination observation period ]
    Symptoms considered to be allergic will be graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale is Grade 1 through 5, the higher the grade, the more severe the allergic reaction.
  • Proportion of participants who experience a systemic allergic reaction ≥Grade 2 to the first dose after adjusting for placebo administration [ Time Frame: Within the 90-minute post- vaccination observation period ]
    Symptoms considered to be allergic will be graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions, Version 3.0. The scale is Grade 1 through 5, the higher the grade, the more severe the allergic reaction.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE COVID19 SARS Vaccinations: Systemic Allergic Reactions to SARS-CoV-2 Vaccinations
Official Title  ICMJE Systemic Allergic Reactions to SARS-CoV-2 Vaccination
Brief 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
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 comparison population without severe allergies or mast cell disorders.

Approximately 2040 HA/MCD and 1360 comparison 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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.
Primary Purpose: Treatment
Condition  ICMJE
  • SARS-CoV Infection
  • COVID-19
  • Allergic Reaction
  • Mast Cell Disorder
Intervention  ICMJE
  • Biological: Moderna COVID-19 Vaccine
    Intramuscular injection
    Other Name: mRNA-1273
  • Biological: Pfizer-BioNTech COVID-19 Vaccine
    Intramuscular injection
    Other Name: BNT162b2
  • Biological: Placebo
    Intramuscular injection
    Other Name: sterile, preservative-free 0.9% Sodium Chloride Injection
Study Arms  ICMJE
  • 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.
    Intervention: Biological: Moderna COVID-19 Vaccine
  • 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.
    Intervention: Biological: Pfizer-BioNTech COVID-19 Vaccine
  • 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.

    Interventions:
    • Biological: Moderna COVID-19 Vaccine
    • Biological: Placebo
  • 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.

    Interventions:
    • Biological: Pfizer-BioNTech COVID-19 Vaccine
    • Biological: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 17, 2021)
3400
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2021
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 16 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 an Emergency Department visit with convincing evidence of a systemic allergic reaction (consistent with CoFAR Grade 3 or higher) to food(s), allergen immunotherapy, or insect venom(s) within the last 5 years
  3. History of documented, immediate allergic reactions to 2 or more unrelated drugs within the last 5 years
  4. 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
  5. History of physician-diagnosed idiopathic anaphylaxis requiring epinephrine or an Emergency Department visit in the last 5 years
  6. 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 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. 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 Fahrenheit, 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 69 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04761822
Other Study ID Numbers  ICMJE DAIT COVID-19-004
NIAID CRMS ID#: 38814 ( Other Identifier: DAIT NIAID )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Participant level data access and additional relevant materials will be made available upon completion of the trial.
Time Frame: After completion of the trial, within 24 months status post database lock.
Access Criteria:

Registration is available for the Immunology Database and Analysis Portal (ImmPort) at: https://www.immport.org/registration. Submit a rationale for the purpose of requesting study data access.

ImmPort is a long-term archive of clinical and mechanistic data, a National Institute of Allergy and Infectious Diseases Division of Allergy, Immunology and Transplantation (NIAID DAIT)-funded data repository. This archive is in support of the NIH mission to share data with the public. Data shared through ImmPort is provided by NIH-funded programs, other research organizations and individual scientists, ensuring these discoveries will be the foundation of future research.

URL: https://www.immport.org/home
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE
  • Immune Tolerance Network (ITN)
  • Rho Federal Systems Division, Inc.
Investigators  ICMJE
Study Chair: James R. Baker Jr., MD Mary H. Weiser Food Allergy Center and Michigan Nanotechnology Institute for Medicine and the Biological Sciences
Study Chair: Rebecca S. Gruchalla, MD, PhD Division of Allergy and Immunology Departments of Internal Medicine and Pediatrics, University of Texas Southwestern
Study Chair: N. Franklin Atkinson Jr., MD Graduate Training Program in Clinical Investigation Associate TP Director, Allergy-Immunology Johns Hopkins Asthma & Allergy Center
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP