Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine.

BACKGROUND: Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. METHODS: This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 µg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. RESULTS: The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. CONCLUSIONS: The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).

Diversity and inclusion in clinical trials: Evolution throughout the development of an mRNA COVID-19 vaccine.

Despite the importance of equitable representation in clinical trials, disparities persist with racial and ethnic minorities remaining largely underrepresented in trial populations. During the coronavirus disease 2019 (COVID-19) pandemic, wherein disease disproportionately affected racial and ethnic minority groups, the necessity for diverse and inclusive representation in clinical trials has been further highlighted. Considering the urgent need for a safe and efficacious vaccine, COVID-19 vaccine clinical trials faced marked challenges in rapidly enrolling participants without forgoing diverse representation. In this perspective, we summarize Moderna's approach toward achieving equitable representation in mRNA-1273 COVID-19 vaccine clinical trials, including the COVID-19 efficacy (COVE) study, a large, randomized, controlled, phase 3 trial of mRNA-1273 safety and efficacy in adults. We describe the dynamics of enrollment diversity throughout the COVE trial and the need for continuous, efficient monitoring and rapid pivoting from initial approaches to address early challenges. Insights gained from our varied and evolved initiatives provide key learnings toward achieving equitable representation in clinical trials, including establishing and listening to a Diversity and Inclusion Advisory Committee, repeatedly engaging with key stakeholders on the necessity for diverse representation, creating and disseminating inclusive materials to all trial participants, establishing methods to raise awareness for interested participants, and enhancing transparency with trial participants to build trust. This work shows that diversity and inclusion in clinical trials can be attained even in the most extreme circumstances and highlights the importance of efforts toward building trust and empowering racial and ethnic minorities with the knowledge to make informed medical treatment decisions.