A clinical trial is currently underway to determine whether people with high allergies or mast cell disorder are at increased risk of an immediate systemic allergic reaction to the Moderna or Pfizer-BioNTech COVID-19 vaccines. A systemic allergic reaction to a vaccine occurs in one or more parts of the body beyond the injection site. If such an allergic reaction occurs in study participants, the researchers will assess whether the reactions occur more frequently in participants with high allergy or mast cell disorder than in participants without a history of allergic disease. In addition, the researchers are studying the biological mechanism behind the reactions and whether a genetic pattern or other factors can predict who is most at risk.
Mast cell disorder is a disease caused by a type of white blood cell called a mast cell that is abnormal, overly active, or both, and which predisposes a person to life-threatening reactions that look like allergic reactions.
"The public was understandably concerned about reports of rare, severe allergic reactions to the Moderna and Pfizer-BioNTech COVID-19 vaccines," said Dr. Anthony S. Fauci, Director of the National Institute for Allergies and Infectious Diseases (NIAID). Part of the National Institutes of Health. “The information gathered during this study will help doctors educate people with high allergies or mast cell disorder about the risks and benefits of receiving these two vaccines. For most people, however, the benefits of COVID-19 vaccination far outweigh the risks. "
The phase 2 study, entitled Systemic Allergic Reactions to SARS-CoV-2 Vaccinations, is sponsored and funded by NIAID. The vaccines are provided by the program led by the U.S. Department of Health and the Department of Defense to develop COVID-19 vaccines and therapeutics. The vaccines are manufactured by Moderna, Inc. of Cambridge, Massachusetts and Pfizer, Inc. of New York.
Moderna and Pfizer-BioNTech's COVID-19 vaccines are the first two emergency COVID-19 vaccines to be approved by the Food and Drug Administration and have been administered to millions of Americans. Most of the rare, severe allergic reactions to these vaccines have occurred in people with a history of allergies. A significant number of these people had previously experienced a life-threatening allergic reaction called anaphylaxis.
The study team will enroll 3,400 adults aged 18 to 69 in up to 35 academic allergy research centers nationwide. Approximately 60% of the study participants, Group 1, must have either a history of severe allergic reactions or a diagnosis of mast cell disorder, while 40% of the participants, Group 2, do not. The specific types of allergic reactions in Group 1 participants relate to food, insect bites, or allergen immunotherapy, and require treatment with a drug called adrenaline. or are immediate allergic reactions to a vaccine or to one or more drugs. These reactions will have occurred in the past 5 years. Group 2 consists of people without a history of allergic reactions or allergic diseases and without a history of mast cell disorder. Approximately two-thirds of the participants in each group will be female, as severe allergic reactions to vaccines in general (and to Moderna and Pfizer-BioNTech's COVID-19 vaccines in particular) have mostly occurred in women.
Participants in each group will randomly receive either the Pfizer BioNTech vaccine (one third of the group); the Moderna vaccine (one third); a placebo followed by the Pfizer BioNTech vaccine (one sixth); or a placebo followed by the Moderna vaccine (one sixth). Initially, neither the participants nor the study team know who is receiving a vaccine or a placebo, or which vaccine is being given. All participants ultimately receive a full two-dose course of either the Pfizer BioNTech vaccine or the Moderna vaccine.
The investigators on site are allergy sufferers who are trained to recognize and treat anaphylaxis. Emergency medication, oxygen, and medical equipment are available to manage allergic reactions as needed. Participants will be observed for at least 90 minutes after each injection if any type of reaction occurs.
Three days after their first injection, participants receive a follow-up call from the study team to schedule their next injection in 21 or 28 days. Three days after the second injection, participants who did not receive a placebo will receive a follow-up call to inform them that they have received a vaccine and which, while participants who have originally received a placebo will be scheduled for their second vaccine dose. The study staff assess the health of the participants during the follow-up calls. All participants will receive their last follow-up call seven days after their last dose.
Researchers will evaluate the proportion of study participants in each group who have systemic allergic reactions to either a dose of the Pfizer BioNTech vaccine or a dose of the Moderna vaccine within 90 minutes of injection. Results are expected in late summer 2021.
Study staff collect blood, urine, and nasal swabs from participants before each injection, and blood and urine after each injection. If a significant number of systemic allergic reactions to one or both vaccines occur during the experiment, the researchers analyze these biological samples to investigate possible mechanisms behind the reactions and to determine whether certain genetic patterns are associated with a higher risk.
Investigators will closely monitor participants' safety throughout the experiment. In addition, an independent data and security monitoring body (DSMB) will review blinded and non-blinded study data during scheduled review sessions to further ensure the safety of study participants.