Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine.

Martha C Nason, Jessica Cowden, Sergio L Vargas, Alfredo Guerreros Benavides, Robert Call, Michael C Keefer, Beth D Kirkpatrick, John Pullman, Tina Tong, Margaret Brewinski Isaacs, David Benkeser, Holly E Janes, Susan Buchbinder, Justin A Green, Elizabeth J Kelly, Jill Maaske, Nancy Mueller, Kathryn Shoemaker, Therese Takas, Richard P Marshall, Menelas N Pangalos, Tonya Villafana, Antonio Gonzalez-Lopez, Edwin DeJesus, Magdalena E Sobieszczyk, Ian Hirsch, Stephanie Sproule, Merlin L Robb, Lawrence Corey, Kathleen M Neuzil, William Hahn, Julie Hunt, Mark J Mulligan, Charlene McEvoy, Ann R Falsey, Michael Hassman, Susan J Little, Barbara A Pahud, Anna Durbin, Paul Pickrell, Eric S Daar, Larry Bush, Joel Solis, Quito Osuna Carr, Temitope Oyedele

Journal: The New England journal of medicine 2021;385(25):2348-2360

PMID: 34587382

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Abstract

BACKGROUND

The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known.

METHODS

In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru.

RESULTS

A total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants). AZD1222 was safe, with low incidences of serious and medically attended adverse events and adverse events of special interest; the incidences were similar to those observed in the placebo group. Solicited local and systemic reactions were generally mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3 to 80.5; P<0.001) and estimated vaccine efficacy was 83.5% (95% CI, 54.2 to 94.1) in participants 65 years of age or older. High vaccine efficacy was consistent across a range of demographic subgroups. In the fully vaccinated analysis subgroup, no severe or critical symptomatic Covid-19 cases were observed among the 17,662 participants in the AZD1222 group; 8 cases were noted among the 8550 participants in the placebo group (<0.1%). The estimated vaccine efficacy for preventing SARS-CoV-2 infection (nucleocapsid antibody seroconversion) was 64.3% (95% CI, 56.1 to 71.0; P<0.001). SARS-CoV-2 spike protein binding and neutralizing antibodies increased after the first dose and increased further when measured 28 days after the second dose.

CONCLUSIONS

AZD1222 was safe and efficacious in preventing symptomatic and severe Covid-19 across diverse populations that included older adults. (Funded by AstraZeneca and others; ClinicalTrials.gov number, NCT04516746.).

Address: From the University of Rochester School of Medicine and Dentistry (A.R.F., M.C.K.) and Rochester Regional Health (A.R.F.), Rochester, and Vagelos College of Physicians and Surgeons, New York Presbyterian Columbia University Irving Medical Center, Department of Medicine, Division of Infectious Diseases (M.E.S.) and the New York University Vaccine Center (M.J.M.), New York - all in New York; Biometrics (I.H.) and Infectious Diseases (J.A.G.), Late-Stage Development, Respiratory and Immunology (R.P.M.), Biopharmaceuticals Research and Development (M.N.P.), AstraZeneca, Cambridge, United Kingdom; Biometrics (S.S., K.S.) and Infectious Diseases, Late-Stage Development, Respiratory and Immunology (J.M., T. Takas, T.V., A.G.-L.), Translational Medicine, Microbial Sciences, Biopharmaceuticals Research and Development (E.J.K.), and Clinical Development, Early Global Development, Oncology Research and Development (N.M.), AstraZeneca, Gaithersburg, the Walter Reed Army Institute of Research, Silver Spring (M.L.R.), the University of Maryland School of Medicine (K.M.N.) and the Johns Hopkins Bloomberg School of Public Health (A.D.), Baltimore, the Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense, Edgewood (J.C.), and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda (T. Tong, M.B.I., M.C.N.) - all in Maryland; the University of Washington (L.C., W.H.) and the Fred Hutchinson Cancer Research Center (L.C., W.H., J.H., H.E.J.), Seattle; HealthPartners Institute, St. Paul, MN (C.M.); Orlando Immunology Center, Orlando (E.D.), and JEM Headlands Research, Lake Worth Beach (L.B.) - both in Florida; Hassman Research Institute, Berlin, NJ (M.H.); the University of California San Diego, La Jolla (S.J.L.), the Lundquist Institute at Harbor-UCLA Medical Center, Torrance (E.S.D.), and the San Francisco Department of Public Health, San Francisco (S.B.) - all in California; Children's Mercy Kansas City, Kansas City, MO (B.A.P.); Tekton Research, Austin (P.P.), and Centex Studies, McAllen (J.S.) - both in Texas; Medpharmics, Albuquerque, NM (Q.O.C.); John H. Stroger, Jr. Hospital of Cook County, Chicago (T.O.); Instituto de Ciencias Biomédicas, Facultad de Medicina Universidad de Chile, Santiago, Chile (S.L.V.); Clínica Internacional Sede Lima, Lima, Peru (A.G.B.); Clinical Research Partners, Richmond, VA (R.C.); the University of Vermont Larner College of Medicine and UVM Medical Center, Burlington (B.D.K.); Mercury Street Medical Group, Butte, MT (J.P.); and the Rollins School of Public Health at Emory University, Atlanta (D.B.).

DOI: 10.1056/NEJMoa2105290

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MeSH Terms: Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, ChAdOx1 nCoV-19, Chile, Double-Blind Method, Female, Humans, Immunogenicity, Vaccine, Male, Middle Aged, Peru, SARS-CoV-2, Spike Glycoprotein, Coronavirus, United States, Vaccine Efficacy, Young Adult