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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04977479
Recruitment Status : Active, not recruiting
First Posted : July 27, 2021
Last Update Posted : July 26, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

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 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.


Condition or disease Intervention/treatment Phase
Systemic Allergic Reaction Biological: Pfizer-BioNTech COVID-19 Vaccine (comirnaty) Other: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
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
Actual Study Start Date : September 8, 2021
Estimated Primary Completion Date : December 30, 2022
Estimated Study Completion Date : December 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Active Vaccine
Participant receives the active mRNA COVID-19 vaccine
Biological: Pfizer-BioNTech COVID-19 Vaccine (comirnaty)
mRNA vaccine for the prevention of COVID-19. Single dose (0.3mL) via IM.

Placebo Comparator: Placebo
All participants crossover and receive active vaccine but which day placebo vs active is given is randomized and blinded.
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.




Primary Outcome Measures :
  1. CoFAR Grade 2 and above reaction regardless of tryptase, or CoFAR grade 1 with elevated tryptase [1.2 X baseline plus 2ng/ml]) [ Time Frame: Days 1 and 2 ]
    Assess the proportion of participants who develop a systemic allergic reaction (Consortium for Food Allergy Research (CoFAR) grade 2 reaction and above regardless of tryptase, or CoFAR grade 1 with elevated tryptase [1.2 X baseline plus 2ng/mL]) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating 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 2ng/mL]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine.


Secondary Outcome Measures :
  1. CoFAR grade 3 reaction and above [ Time Frame: Days 1 and 2 ]
    Assess the proportion of participants who develop a severe systemic allergic reaction (CoFAR Grade 3 reaction or higher regardless of tryptase) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating 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 2ng/mL]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine.

  2. CoFAR grade 1 or 2 reaction regardless of tryptase [ Time Frame: Days 1 and 2 ]
    Assess the proportion of participants who develop a mild-moderate allergic reaction (CoFAR Grade 1 or 2 reaction regardless of tryptase) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating 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 2ng/mL]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine.

  3. Brighton Collaboration Criteria Levels 1-3 [ Time Frame: Days 1 and 2 ]
    Assess the proportion of participants with anaphylactic reactions (Levels 1-3) per Brighton Collaboration Criteria to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine.

  4. CoFAR Grade 2 and above reaction regardless of tryptase, or CoFAR grade 1 with elevated tryptase [1.2 X baseline plus 2ng/ml]) compared to rates following placebo administration [ Time Frame: Days 1 and 2 ]
    Assess the proportion of participants who develop a systemic allergic reaction (CoFAR Grade 2 reaction or higher regardless of tryptase OR Grade 1 reaction with elevated tryptase [1.2 X baseline plus 2ng/mL]) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating 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 2ng/mL]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine compared to the rate of these reactions following placebo administration

  5. Allergic reaction at any grade [ Time Frame: Days 1 and 2 ]
    Compare the severity of allergic reactions to the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine to the severity of the reaction following administration of a subsequent dose of the Pfizer-BioNTech vaccine in individuals who experienced a systemic allergic reaction (CoFAR grade 2 reaction and above regardless of tryptase, or CoFAR grade 1 with elevated tryptase [1.2 X baseline plus 2ng/mL]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   16 Years to 69 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04977479


Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Pamela A Guerrerio, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT04977479    
Other Study ID Numbers: 10000460
000460-I
First Posted: July 27, 2021    Key Record Dates
Last Update Posted: July 26, 2022
Last Verified: July 21, 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
polyethylene glycol (PEG)
Pfizer-BioNTech COVID-19 vaccine
Moderna Covid-19 vaccine
Consortium for Food Allergy Research (CoFAR)
SARS-CoV-2
Comirnaty
Additional relevant MeSH terms:
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COVID-19
Hypersensitivity
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Immune System Diseases