- Moderna has begun the first large efficacy trial of an experimental coronavirus vaccine in the U.S., starting Monday a 30,000-volunteer, placebo-controlled study that will be run in collaboration with the U.S. government.
- Through the Biomedical Advanced Research and Development Authority, the U.S. pledged as much as $472 million in additional funding for Moderna to support the study, nearly double a previous contract signed in April. The new award followed discussions with government scientists, after which Moderna chose to run a "significantly larger" trial than it had planned to before, the company said.
- Moderna's trial, dubbed COVE, is the first of an expected five like-sized studies to begin in the U.S. over the new few months. Vaccines from AstraZeneca, BioNTech and partner Pfizer, Johnson & Johnson and Novavax could each soon enter Phase 3 testing, creating a research task that trial leaders have called "unprecedented" given the speed and urgency at which it's being done.
The early studies of coronavirus vaccines were designed to determine whether the shots are safe and encouraging enough to test further. Researchers have met that goal. Since May, preliminary results made public have shown four vaccines can spur an immune response without any extreme side effects.
Critical questions still remain, however. Perhaps the biggest is whether the immune responses observed actually result in protection against either infection or coronavirus disease and, if so, for how long. Monday's announcement from Moderna starts an historic push by multiple drugmakers, researchers and government bodies to get an answer to that question in record time.
The design of Moderna's study, called COVE, sets the stage for what's to come. Some 30,000 volunteers aged 18 and up will be enrolled, randomized and split into two evenly sized groups. One group will get the vaccine, known as mRNA-1273, and the other a placebo. They'll receive two shots — one on the first day, and a second four weeks later — and be tracked for up to two years. Participants will receive the "middle," 100 microgram dose that Moderna has tested in clinical trials so far.
The study's main goal is to prevent symptomatic COVID-19 cases — specifically, according to FDA guidance, leading to least 50% fewer cases than placebo — that start 14 days or more after the second shot. Early tests of Moderna's vaccine have shown antibodies that might neutralize SARS-CoV-2 don't materialize for a couple weeks, and don't peak until shortly after participants get a booster shot.
Secondary measures to be tested in the trial include whether the vaccine prevents infection with SARS-CoV-2 and hospitalization with severe disease.
A major challenge Moderna and others will face in running large trials amid a pandemic is to quickly enroll a diverse group of people, not just young, largely white and healthy individuals.
In a statement, Moderna noted that it chose roughly 100 trial sites with "representative demography," and said it will work with those sites and local community leaders to ensure study volunteers come from "communities at highest risk for COVID-19 and of our diverse society."
That work is being done with the help of the National Institute of Health's COVID-19 Prevention Network, or CoVPN, a sprawling initiative announced in July to merge multiple existing NIH-backed clinical trial networks and coordinate coronavirus vaccine studies through them.
Speaking with BioPharma Dive recently, CoVPN leaders were confident they could recruit enough at-risk enrollees for each trial. They plan to use an online registry, while leaning on community leaders and sports organizations to help with outreach.
Still, they noted the difficulty of rapidly earning the trust of many people who may be skeptical of biomedical research.
"Trust is built over time, and that is very challenging because we don't have the time," said Kathleen Neuzil, who co-runs the vaccine testing in CoVPN and is the director of the University of Maryland School of Medicine's Center for Vaccine Development and Global Health.
Moderna has now received nearly $1 billion from BARDA to support its work, a significant sum that trails only the awards given to AstraZeneca and Novavax among funding grants made via the Trump administration's ambitious "Operation Warp Speed" project.
The April contract Moderna inked was to scale up manufacturing of mRNA-1273 and for clinical development, but with a "smaller anticipated number of participants" in its Phase 3 trial. Moderna's current study plans left a "gap in funding" that the new contract closes, the company said.
Moderna didn't respond to a request for comment regarding the specifics of its original plans and how they've changed.
The biotech is using a recent $1.3 billion stock offering and a deal with Swiss manufacturer Lonza to make vaccine doses "at risk," before knowing whether mRNA-1273 works. Moderna aims to deliver about 500 million doses, and potentially up to 1 billion, per year by 2021.
Since Moderna's vaccine requires two shots, those totals would be sufficient for some 250 million to 500 million people.