Early next month, the first COVID-19 vaccine candidate will enter a Phase 3 trial, the final phase before potential FDA approval. Moderna’s mRNA-1273, an mRNA vaccine candidate, is expected to enter the Phase 3 study the first week of July.
The randomized, placebo-controlled trial, conducted in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), is expected to include 30,000 participants from sites mostly in the United States, but will also comprise some international sites. Trial participants will be diverse in both ethnicity and age. The majority will be 18- to 55-year-olds, but the trial will also recruit elderly persons and those with underlying co-morbidities.
“We want to get as many datapoints as possible,” Anthony Fauci, NIAID director, told JAMA earlier this month. “Even if you have 30,000 people, it could take months and months to get an answer if a site is a location with a small surge of cases.”
The trial’s main goal is the prevention of symptomatic COVID-19, with secondary targets of preventing severe COVID-19 leading to hospitalization and halting initial infection by SARS-COV-2. mRNA-1273 has already completed the Phase 1 study and has finalized enrollment of younger adults in the Phase 2 study.
Based on results of the Phase 1 study, the 100 μg dose level was chosen as the optimal dose level to maximize the immune response while minimizing adverse reactions. Participants in the Phase 1 study will be involved in long-term follow-up. The NIH will soon submit the Phase 1 data to a peer-reviewed clinical publication, as well.
Moderna’s Phase 2 study is evaluating the safety, reactogenicity and immunogenicity of two vaccinations of mRNA-1273 given 28 days apart. Six hundred participants, 300 aged 18-54 and 300 ages 55 and above, will received a placebo, a 50 μg or a 100 μg dose at both vaccinations. Participants will be followed through 12 months after the second vaccination.
If mRNA-1273 is approved for public health use, the conversation immediately turns to available doses. At 100 μg, Moderna says it can deliver approximately 500 million doses per year. Through a strategic collaboration with Lonza, Moderna may be able to manufacture up to 1 billion doses per year. Fauci said Moderna will start manufacturing doses of the vaccine even before it’s proven efficacious in an effort to get ahead.
While mRNA-1273 is the first COVID-19 vaccine to hit Phase 3 trials, it soon won’t be the only one. A vaccine candidate from AstraZeneca and University of Oxford is expected to enter Phase 3 trials at the same time as the Moderna vaccine, or very shortly after. In fact, according to Fauci, there are four to five vaccines that are getting close to Phase 3 trials—a necessary step toward FDA approval.
“I’m cautiously optimistic that the multiple candidates we have with different platforms will give a vaccine that shows a degree of efficacy that would make it deployable. Even though the number of deaths is profound, the majority of people make an immune response, which clears the virus. That tells us the body is capable of making an immune response to clear the virus, and that’s a pretty good proof-of-concept. However, there is never a guarantee you are going to get an effective vaccine,” Fauci told JAMA Editor-in-Chief Howard Bauchner.
On May 11, 2020, the FDA granted its Fast Track designation to Moderna’s mRNA-1273 under an Investigational New Drug application.