Pfizer and BioNTech have begun dosing participants in a U.S. clinical trial of their COVID-19 vaccine candidates. The dose-escalation stage of the trial will enroll up to 360 subjects, initially out of sites in New York and Maryland.
A study of the vaccine candidate, BNT162, in BioNTech’s home country of Germany completed dosing of its first cohort of subjects late last month, less than a week after giving the shot to the first of the 12 people enrolled in the arm. Now, BioNTech and Pfizer have brought the development program stateside, working with researchers at NYU Grossman School of Medicine and the University of Maryland School of Medicine to test the vaccine.
The U.S. clinical trial is studying four variants of the vaccine, code-named a1, b1, b2 and c2, to quickly determine which combination of mRNA format and target antigen holds the most promise. Pfizer and BioNTech are assessing candidates that contain uridine-containing mRNA, nucleoside-modified mRNA or self-amplifying mRNA.
Under the current protocol, the partners plan to test each vaccine variant at three dose levels and as part of either single- or two-dose regimens. At each dose level, investigators will initially administer the vaccine to adults aged 18 to 55 years old. After gathering safety and immunogenicity data in that lower-risk demographic, the researchers will start giving the vaccine to people aged 65 to 85 years old.
Initially, investigators will enroll 15 subjects at each dose level into a sentinel cohort, cutting the risk of large numbers of people being harmed by an unforeseen adverse event. The study will analyze the hematology and chemistry laboratory values of sentinel subjects the day and week after dosing. Data from sentinel cohorts will be part of the first stage of the clinical trial, which is designed to identify the preferred vaccine candidate, dose level and number, and schedule of administration.
After making those decisions, Pfizer and BioNTech will start a second, expanded cohort stage. Finally, the partners will move into a large-scale study of the final vaccine candidate. The trial also features a placebo arm for each age cohort. Pfizer plans to expand the trial to sites across the U.S. in early July, positioning it to potentially enroll more than 8,000 people.
The design could give Pfizer and BioNTech the ability to quickly move through the different phases of clinical development, thereby enabling them to get a potentially pandemic-ending vaccine to market sooner. However, clinical development is only one part of the challenge of creating a vaccine to end the pandemic. Pfizer and BioNTech also need to be able to make enough of the product to support mass-vaccination initiatives.
By switching four Pfizer sites—three in the U.S. and one in Belgium—to BNT162 production and making use of BioNTech facilities in Germany, the partners think they can manufacture millions of doses this year and ramp up output into the hundreds of millions in 2021. Other groups including Moderna and CanSino Biologics also have COVID-19 vaccines in clinical development.
Editor's note: This article has been updated with enrollment target data shared by a spokesperson for Pfizer.