Fast enrollment of the right patient populations will be critical to quickly conducting Phase III trials of COVID-19 vaccines and this will likely mean taking concerted steps to reach out to populations that can be harder to recruit for clinical trials, drug industry leaders said on a recent New York Academy of Sciences webinar.
Moderna Inc.’s Chief Medical Officer Tal Zaks said concern around whether his company’s COVID-19 clinical trial can reach “the right population that should benefit the most,” is keeping him up at night. “It is not the concern of is it going to be safe; it is not the concern of is it going to work,” he said on 18 June at the NYAS webinar on when a COIVD-19 vaccine will be ready.
Moderna plans to enroll about 30,000 US patients for its Phase 3 trial of its vaccine, mRNA-1273, which is slated to commence in July.
Zaks said he believes it will be fairly easy to find that many patients willing to partake in the study, but many of those eager to volunteer are unlikely to meet trial endpoints in a fast-enough time frame, either because they are not at high-risk for contacting the disease due to their ability to social distance or because they are not at high-risk for experiencing a particularly bad course of disease.
“People would line up around the block,” if Moderna launched a site where Zaks lives in Newton, MA, he said. “But you’d find people like me who are sitting at home all day.” This means those people would be at very low risk of contacting COVID-19.
To help recruit the right population Zaks said Moderna has “very explicitly” designed the protocol to include a heterogeneous mix of sites and define the patient population as “those who are at risk of getting infected and at risk of severe outcomes if they get infected.”
Populations that are being most heavily hit by serve COVID-19 in the US including minorities and the elderly tend to be under-represented in trials for FDA approval. In the US it has long been thought that the Tuskegee syphilis stuck or other examples of unethical research on minorities contributes to the current low rates of minority population participation in trials and there is also newer concerns that physicians may be less likely to communicate with minorities about trial opportunities. (Also see “Expanding The Tent: Improving Trial Participation Among Under-Represented Patient Populations” – In Vivo, 8 Apr, 2020.)
Moderna is working with the US National Institutes of Allergy and Infectious Disease’s network to pull on their HIV experience of reaching out to under-served populations and improve community trust in vaccines being offered.
“The thing that keeps me up at night is that because of varying levels of access and education and trust in the system, our best intentions will actually not get translated into the reality of a clinical trial,” Zaks said.
Moderna is going to proactively look on a site-by-site and investigator-by-investigator level to make sure that the locations they pick are capable of recruiting the needed populations, and Zaks said he will also be asking his team to give him periodic updates on the makeup of the trial. If diversity goals aren’t being met they will stop enrollment at those sites. Zaks also said he expects the exclusionary criteria for the trial to be limited and pledged to make the Phase III trial protocol publicly available once it is approved by its Institutional Review Board.
The positive side of the recruitment challenge is that the need to get to trial endpoints fast during a pandemic should help ensure studies meet diversity goals, said Kathrin Jansen, senior vice president and head of vaccine research and development at Pfizer Inc., on the webinar.
Bioethicists have been pushing for COVID-19 trials to include the populations that will be treated with the vaccine once approved and not to rely on
