N Engl J Med . Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase

[tetano]

N Engl J Med


. 2021 Sep 22.
doi: 10.1056/NEJMoa2113017. Online ahead of print.
Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase


Hana M El Sahly ¹ , Lindsey R Baden ¹ , Brandon Essink ¹ , Susanne Doblecki-Lewis ¹ , Judith M Martin ¹ , Evan J Anderson ¹ , Thomas B Campbell ¹ , Jesse Clark ¹ , Lisa A Jackson ¹ , Carl J Fichtenbaum ¹ , Marcus Zervos ¹ , Bruce Rankin ¹ , Frank Eder ¹ , Gregory Feldman ¹ , Christina Kennelly ¹ , Laurie Han-Conrad ¹ , Michael Levin ¹ , Kathleen M Neuzil ¹ , Lawrence Corey ¹ , Peter Gilbert ¹ , Holly Janes ¹ , Dean Follmann ¹ , Mary Marovich ¹ , Laura Polakowski ¹ , John R Mascola ¹ , Julie E Ledgerwood ¹ , Barney S Graham ¹ , Allison August ¹ , Heather Clouting ¹ , Weiping Deng ¹ , Shu Han ¹ , Brett Leav ¹ , Deb Manzo ¹ , Rolando Pajon ¹ , Florian Schödel ¹ , Joanne E Tomassini ¹ , Honghong Zhou ¹ , Jacqueline Miller ¹ , COVE Study Group



Affiliations

• PMID: 34551225
• DOI: 10.1056/NEJMoa2113017

Abstract

Background: At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase. Final analyses of efficacy and safety data from the blinded phase of the trial are reported.
Methods: We enrolled volunteers who were at high risk for Covid-19 or its complications; participants were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo, 28 days apart, at 99 centers across the United States. 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 the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The data cutoff date was March 26, 2021.
Results: The trial enrolled 30,415 participants; 15,209 were assigned to receive the mRNA-1273 vaccine, and 15,206 to receive placebo. More than 96% of participants received both injections, 2.3% had evidence of SARS-CoV-2 infection at baseline, and the median follow-up was 5.3 months in the blinded phase. Vaccine efficacy in preventing Covid-19 illness was 93.2% (95% confidence interval [CI], 91.0 to 94.8), with 55 confirmed cases in the mRNA-1273 group (9.6 per 1000 person-years; 95% CI, 7.2 to 12.5) and 744 in the placebo group (136.6 per 1000 person-years; 95% CI, 127.0 to 146.8). The efficacy in preventing severe disease was 98.2% (95% CI, 92.8 to 99.6), with 2 cases in the mRNA-1273 group and 106 in the placebo group, and the efficacy in preventing asymptomatic infection starting 14 days after the second injection was 63.0% (95% CI, 56.6 to 68.5), with 214 cases in the mRNA-1273 group and 498 in the placebo group. Vaccine efficacy was consistent across ethnic and racial groups, age groups, and participants with coexisting conditions. No safety concerns were identified.
Conclusions: The mRNA-1273 vaccine continued to be efficacious in preventing Covid-19 illness and severe disease at more than 5 months, with an acceptable safety profile, and protection against asymptomatic infection was observed. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).