A clinical trial evaluating whether individuals who are highly allergic or have a mast cell disorder are at increased risk for an immediate, systemic allergic reaction to the Moderna or Pfizer-BioNTech COVID-19 vaccines has been initiated.
The multicenter, randomized, initially blinded, phase 2 Systemic Allergic Reactions to SARS-CoV-2 Vaccination trial (ClinicalTrials.gov: NCT04761822) will enroll 3400 adults aged 18 to 69 years, of whom approximately 60% must have either a history of severe allergic reactions or a diagnosis of a mast cell disorder (group 1), while 40% will not (group 2). As severe allergic reactions have mostly occurred in women, approximately two-thirds of participants in each group will be female.
Group 1 will include individuals with allergic reactions related to food, insect stings or allergen immunotherapy that require treatment with epinephrine, as well as those with previous immediate allergic reaction to a vaccine or to 1 or more drugs. These reactions must have occurred within the past 5 years.
Participants will be randomly assigned 2:2:1:1 to receive either the Pfizer-BioNTech COVID-19 vaccine, the Moderna COVID-19 vaccine, placebo followed by the Pfizer-BioNTech COVID-19 vaccine, or placebo followed by the Moderna COVID-19 vaccine. All participants will be initially-blinded during the first visit.
Due to the different dosing schedules for each vaccine, participants will know which vaccine has been assigned once their second visit is scheduled. Participants will be unblinded during a follow-up call scheduled 3 days after the second injection. At the end of the study, all participants will receive a full 2-dose series of either vaccine. The primary endpoint of the trial is the proportion of participants who experience a systemic allergic reaction within 90 minutes post-injection to either dose of the Pfizer-BioNTech or Moderna COVID-19 vaccines.
Investigators will also analyze the biological mechanisms for the reactions and whether certain genetic patterns are associated with higher risk. An independent data and safety monitoring board (DMSB) will review study data to ensure the safety of participants. The trial is sponsored and funded by the National Institute of Allergy and Infectious Diseases (NIAID).
Trial results are expected in late summer 2021.
“The public understandably has been concerned about reports of rare, severe allergic reactions to the Moderna and Pfizer-BioNTech COVID-19 vaccines,” said Anthony S. Fauci, MD, director of the NIAID, part of the National Institutes of Health. “The information gathered during this trial will help doctors advise people who are highly allergic or have a mast cell disorder about the risks and benefits of receiving these 2 vaccines. However, for most people, the benefits of COVID-19 vaccination far outweigh the risks.”
NIH begins study of allergic reactions to Moderna, Pfizer-BioNTech COVID-19 vaccines. [press release]. Bethesda, MD: National Institutes of Health; April 7, 2021.