This article is part of Harvard Medical School’s continuing coverage of medicine, biomedical research, medical education and policy related to the SARS-CoV-2 pandemic and the disease COVID-19.
A candidate vaccine for preventing COVID-19 is advancing to a 30,000-participant phase 3 trial starting July 27, and Brigham and Women’s Hospital will play two key roles in the trial.
The phase 3 COVE study will evaluate mRNA-1273, a vaccine candidate against COVID-19 manufactured by Moderna. The study will enroll participants at locations throughout the United States, with Brigham and Women’s serving as a clinical research site as part of the COVID-19 Prevention Network (CoVPN), funded by the National Institutes of Health.
Lindsey Baden, HMS associate professor of medicine and an infectious disease specialist at Brigham and Women’s, will serve as co-principal investigator for the study.
“This is the first phase 3 trial that will test the effectiveness of a vaccine against COVID-19, and we’ve been working diligently across industry, academia and government to pave a path for launching this trial rapidly and safely,” said Baden, an expert in vaccine development for viral diseases.
“Our goal has been to not only launch this important trial but also to develop a rapid, high-quality process for vaccine trials that are to come.”
Baden, an expert in the development of novel diagnostics and therapeutics for viral diseases that disproportionately affect high-risk patients, is the director of the Center for Clinical Investigation at Brigham and Women’s and director of the BWH/DFCI Infectious Diseases Immune-Compromised Host inpatient and outpatient consultative services.
In addition, he is the vaccine clinical research site leader at Brigham and Women’s of the NIAID-funded Harvard HIV Vaccine Clinical Trials Unit and director of the Connector program at Harvard Catalyst, funded by the NIH's National Center for Advancing Translational Sciences.
For 20 years, Brigham and Women’s, under Baden’s leadership, has been part of the HIV Vaccine Trials Network (HVTN), an NIH-funded global network of sites conducting clinical studies related to HIV vaccine development. Earlier this year, the NIH determined that several NIH-funded clinical trials networks, including the HVTN, would come together to answer important infectious disease questions related to COVID-19 under the CoVPN.
Brigham and Women’s, along with clinical research study sites across the United States, became part of this network. Sites for the vaccine studies were selected through an NIH mechanism, and Baden was chosen by the leadership of the CoVPN to be co-principal investigator of the upcoming mRNA phase 3 vaccine trial based upon his clinical research experience and his knowledge of COVID-19.
Additional phase 3 vaccine trials are being planned by the COVPN in conjunction with pharmaceutical companies.
The COVE study is part of Operation Warp Speed (OWS), which aims to deliver 300 million doses of a safe, effective vaccine for COVID-19 by early 2021.
OWS represents a partnership among components of the U.S. Department of Health and Human Services, including the Centers for Disease Control and Prevention, Food and Drug Administration, NIH, BARDA, and Department of Defense.
The COVE study is largely funded by the U.S. government through the Biomedical Advanced Research and Development Authority (BARDA) and National Institute of Allergy and Infectious Diseases.
The COVE study is designed to primarily evaluate the effectiveness and safety of mRNA-1273 and its ability to prevent COVID-19. Participants will be followed for up to two years after the second dose of the vaccine.
The trial is expected to enroll 30,000 participants who will be randomized to receive either two 100 microgram injections of mRNA-1273 or two shots of a saline placebo. Trial volunteers will receive two intramuscular injections about 28 days apart. The trial is blinded, meaning that neither the investigators nor the participants will know who is assigned to which group.
Volunteers must provide informed consent to participate in the trial. They will be asked to provide a nasopharyngeal swab and a blood sample at an initial screening visit and additional blood samples at specified time points after each vaccination and over the two years following the second vaccination. Scientists will examine blood samples in the laboratory to detect and quantify immune responses to SARS-CoV-2.
Investigators will closely monitor participant safety.
The target population for this study are adults whose locations or circumstances put them at considerable risk of exposure to COVID-19. The primary endpoint to gauge vaccine efficacy will be whether it prevents the development of symptomatic disease.
Key secondary endpoints include prevention of severe disease (defined by the need for hospitalization) and prevention of infection by the virus that causes COVID-19, SARS-CoV-2.
A preliminary report on data from the phase 1 trial of mRNA-1273 was recently published in The New England Journal of Medicine, which found evidence that the vaccine induced an anti–SARS-CoV-2 immune response in all 45 participants.