Novavax has added crossover arms to late-phase clinical trials of its COVID-19 vaccine. The action will enable participants in the placebo cohorts of the original trials to get vaccinated without unblinding the studies.
Participants in the 15,000-subject U.K. trial and 30,000-subject U.S.-Mexico study, which is yet to post data, will be offered the chance to get an additional round of injections. People who originally got a placebo will get two doses of the vaccine, and people who originally got the vaccine will receive two doses of placebo.
Novavax has taken a different approach to the South African phase 2b, where the prevalence of the B.1.351 variant contributed to weaker efficacy data than in the U.K. Placebo participants will still get the vaccine, but subjects in the original vaccine arm will also get a booster dose of NVX-CoV2373.
The design of the South African crossover trial will enable Novavax to evaluate whether an additional dose of its vaccine improves protection against B.1.351. The variant makes up a far smaller proportion of all COVID-19 cases in the U.K. and U.S.
Across all three trials, Novavax will conduct the crossover stages without unblinding the studies. The approach enables Novavax to address the ethical concern about leaving people unprotected during a pandemic while retaining the ability to assess efficacy. Novavax plans to follow participants for up to two years to assess the durability of protection. Participants have the option to become unblinded and receive a vaccine through their national immunization campaigns.
Novavax’s approach differs from those of other COVID-19 vaccine developers, which articulated their plans to the FDA as part of the emergency use authorization process. Pfizer-BioNTech and Moderna proposed allowing participants who become eligible for vaccination under real-world immunization programs to request to be unblinded. Johnson & Johnson suggested an open-label crossover.
The International Coalition of Medicines Regulatory Authorities has previously recommended that COVID-19 vaccine clinical trials “proceed as initially planned with a follow-up of at least one year or more from completion of assigned doses.” However, the efficacy of the vaccines and intensification of the COVID-19 crisis over the winter created pressure to get placebo recipients vaccinated.
Novavax articulated its crossover plans, which have been discussed by participants online for more than one month, alongside an update on the testing of its NVX-CoV2373 vaccine in children. The biotech plans to add pediatric and adolescent arms to its U.S.-Mexico study in the second quarter.