mRNA-1273, a COVID-19 vaccine candidate, has met primary efficacy endpoint in the first interim analysis of the phase 3 COVE study
Moderna has announced that the independent, NIH-appointed Data Safety Monitoring Board ( DSMB ) for the phase 3 study of mRNA-1273, a vaccine candidate against COVID-19, has informed Moderna that the trial has met the statistical criteria pre-specified in the study protocol for efficacy, with a vaccine efficacy of 94.5%.
This study, known as the COVE study, enrolled more than 30,000 participants in the U.S. and is being conducted in collaboration with the National Institute of Allergy and Infectious Diseases ( NIAID ), part of the National Institutes of Health ( NIH ), and the Biomedical Advanced Research and Development Authority ( BARDA ), part of the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services.
The primary endpoint of the COVE study is based on the analysis of COVID-19 cases confirmed and adjudicated starting two weeks following the second dose of vaccine.
This first interim analysis was based on 95 cases, of which 90 cases of COVID-19 were observed in the placebo group versus 5 cases observed in the mRNA-1273 group, resulting in a point estimate of vaccine efficacy of 94.5% ( p less than 0.0001 ).
A secondary endpoint analyzed severe cases of COVID-19 and included 11 severe cases ( as defined in the study protocol ) in this first interim analysis.
All 11 cases occurred in the placebo group and none in the mRNA-1273 vaccinated group.
The 95 COVID-19 cases included 15 older adults ( ages 65+ ) and 20 participants identifying as being from diverse communities ( including 12 Hispanic or LatinX, 4 Black or African Americans, 3 Asian Americans and 1 multiracial ).
The interim analysis included a concurrent review of the available COVE study safety data by the DSMB, which did not report any significant safety concerns.
A review of solicited adverse events indicated that the vaccine was generally well tolerated.
The majority of adverse events were mild or moderate in severity.
Grade 3 ( severe ) events greater than or equal to 2% in frequency after the first dose included injection site pain ( 2.7% ), and after the second dose included fatigue ( 9.7% ), myalgia ( 8.9% ), arthralgia ( 5.2% ), headache ( 4.5% ), pain ( 4.1% ) and erythema/redness at the injection site ( 2.0% ). These solicited adverse events were generally short-lived.
Preliminary analysis suggests a broadly consistent safety and efficacy profile across all evaluated subgroups.
The phase 3 COVE trial is a randomized, 1:1 placebo-controlled study testing mRNA-1273 at the 100 µg dose level in 30,000 participants in the U.S., ages 18 and older.
The primary endpoint is the prevention of symptomatic COVID-19 disease. Key secondary endpoints include prevention of severe COVID-19 disease and prevention of infection by SARS-CoV-2.
The COVE study was designed in collaboration with the FDA and NIH to evaluate Americans at risk of severe COVID-19 disease and completed enrollment of 30,000 participants ages 18 and older in the U.S. on October 22, including those at high risk of the severe complications of COVID-19 disease.
The COVE study includes more than 7,000 Americans over the age of 65. It also includes more than 5,000 Americans who are under the age of 65 but have high-risk chronic diseases that put them at increased risk of severe COVID-19, such as diabetes, severe obesity and cardiac disease. These medically high-risk groups represent 42% of the total participants in the COVE study.
The study also included communities that have historically been under-represented in clinical research and have been disproportionately impacted by COVID-19. The study includes more than 11,000 participants from communities of color, representing 37% of the study population, which is similar to the diversity of the U.S. at large. This includes more than 6,000 participants who identify as Hispanic or LatinX, and more than 3,000 participants who identify as Black or African American.
mRNA-1273 is an mRNA vaccine against COVID-19 encoding for a prefusion stabilized form of the Spike ( S ) protein, which was co-developed by Moderna and investigators from NIAID’s Vaccine Research Center. ( Xagena )
Source: Moderna, 2020