A phase 3 clinical trial designed to assess whether an investigational vaccine can prevent symptomatic coronavirus disease 2019 (COVID-19) in adults has started. The vaccine, known as mRNA-1273, was jointly developed by Cambridge, Massachusetts-based biotech company Moderna, Inc. and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The trial, to be conducted at U.S. clinical research sites, is expected to enroll approximately 30,000 adult volunteers who do not have COVID-19.
“Although facial coatings, physical distancing, and adequate isolation and quarantine of infected people and contacts can help mitigate SARS-CoV-2 spread, we urgently need a safe and effective preventive vaccine to ultimately control this pandemic, “said NIAID Director Anthony S. Fauci, MD.” Initial clinical trial results indicate that the investigational mRNA-1273 vaccine is safe and immunogenic, supporting the initiation of a phase 3 clinical trial. This scientifically rigorous, randomized, placebo-controlled trial is designed to determine whether the Vaccine can prevent COVID-19 and how long such protection can last. “
Moderna leads the trial as a regulatory sponsor and provides the investigational vaccine for the trial. The Biomedical Advanced Research and Development Authority (BARDA) of the Office of the Assistant Secretary for Preparedness and Response of the US Department of Health and Human Services and NIAID are providing financial support for the trial. The vaccine efficacy trial is the first to be implemented under Operation Warp Speed, a multi-agency collaboration led by HHS that aims to accelerate the development, manufacturing, and distribution of medical countermeasures for COVID-19.
“Having a safe and effective vaccine distributed by the end of 2020 is a difficult goal, but it is the right goal for the American people,” said NIH Director Francis S. Collins, MD, Ph.D. “Launching this Phase 3 test in record time while upholding the strictest security measures demonstrates American ingenuity at its best and what can be done when stakeholders come together with unassailable objectivity toward a common goal” .
The NIH Coronavirus Prevention Network (CoVPN) will participate in conducting the trial. The network brings together the expertise of existing NIAID-supported clinical research networks. The candidate mRNA-1273 vaccine will be evaluated at approximately 89 clinical research sites in the United States, 24 of which are part of the CoVPN. Researchers will use public health data and incidence trajectory models to identify sustained high incidence areas and emerging hot spots, so sites near these locations can be prioritized for enrollment.
“Thanks to the leadership of President Trump and the hard work of American scientists, the investigational vaccine developed by NIH and Moderna has reached this Phase 3 trial at a record pace,” said HHS Secretary Alex Azar. “Operation Warp Speed is supporting a portfolio of vaccines as the NIH / Moderna candidate so that, if the results of clinical trials meet the FDA gold standard, these products can reach Americans without delay in one day. “
NIAID scientists developed the SARS-CoV-2 (S-2P) spike stabilized immunogen. SARS-CoV-2 is the virus that causes COVID-19; The spike protein on its surface facilitates entry into a cell. Moderna mRNA-1273 uses mRNA (messenger RNA) delivery platform to encode an S-2P immunogen. The investigational vaccine directs cells in the body to express the spike protein to elicit a broad immune response. A phase 1 clinical trial found that the candidate vaccine is safe, generally well tolerated, and capable of inducing antibodies with high levels of virus neutralizing activity. Moderna began the Phase 2 trial of the vaccine in May 2020.
Hana M. El Sahly, MD, principal investigator for the NIAID-funded Clinical Research Consortium on Infectious Diseases site at Baylor College of Medicine in Houston; Lindsey R. Baden, MD, principal investigator for the NIAID-funded Harvard HIV Vaccine Clinical Trials Unit at Brigham and Women’s Hospital in Boston; and Brandon Essink, MD, principal investigator and chief medical officer for Meridian Clinical Research, will serve as co-principal investigators for the Phase 3 trial of mRNA-1273.
As part of the Public-Private Partnership Accelerating Therapeutic Interventions and Vaccines COVID-19 (ACTIV), the NIH and other HHS agencies and government partners, in collaboration with representatives of academia, philanthropic organizations, and numerous biopharmaceutical companies, advised on the Test protocol design and endpoints to ensure a harmonized approach across multiple vaccine efficacy trials.
The trial is designed to assess the safety of mRNA-1273 and to determine if the vaccine can prevent symptomatic COVID-19 after two doses. As secondary objectives, the trial also aims to study whether the vaccine can prevent severe COVID-19 or laboratory-confirmed SARS-CoV-2 infection with or without symptoms of the disease. The trial also seeks to answer whether the vaccine can prevent death from COVID-19 and whether just one dose can prevent symptomatic COVID-19, among other goals.
Test volunteers will receive two intramuscular injections approximately 28 days apart. Participants will be randomly assigned 1: 1 to receive two injections of 100 micrograms (mcg) of mRNA-1273 or two injections of a saline placebo. The trial is blinded, so researchers and participants will not know who is assigned to which group.
Volunteers must give their informed consent to participate in the trial. They will be asked to provide a nasopharyngeal swab and blood sample at an initial screening visit and additional blood samples at specific time points after each vaccination and for two years after the second vaccination. Scientists will examine blood samples in the laboratory to detect and quantify immune responses to SARS-CoV-2.
The researchers will closely monitor the safety of the participants. Participants will be called after each vaccination to discuss any symptoms and will be provided with a diary to record symptoms and a thermometer for temperature readings.
If a participant is suspected of having COVID-19, they will be asked to provide a nasal swab for testing within 72 hours. If the test is positive for SARS-CoV-2 infection, the participant will be closely followed and referred for medical attention if symptoms worsen. Participants will be asked to provide a daily assessment of symptoms through resolution and saliva samples will be taken periodically, so that researchers can test for SARS-CoV-2 infection.
Study investigators will periodically review trial safety data. An independent data and safety monitoring board (DSMB) will review the blinded and non-blinded data, including safety data and COVID-19 cases in both groups, at scheduled data review meetings.
Adults interested in joining this study can visit www.coronaviruspreventionnetwork.org or visit ClinicalTrials.gov and search for identifier NCT04470427 to find a study center to volunteer. ClinicalTrials.gov includes a complete list of study locations.
