Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine,The New England Journal of Medicine

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Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine
The New England Journal of Medicine ( IF 96.2 ) Pub Date : 2021-09-29 , DOI: 10.1056/nejmoa2105290
Ann R Falsey ₁ , Magdalena E Sobieszczyk ₁ , Ian Hirsch ₁ , Stephanie Sproule ₁ , Merlin L Robb ₁ , Lawrence Corey ₁ , Kathleen M Neuzil ₁ , William Hahn ₁ , Julie Hunt ₁ , Mark J Mulligan ₁ , Charlene McEvoy ₁ , Edwin DeJesus ₁ , Michael Hassman ₁ , Susan J Little ₁ , Barbara A Pahud ₁ , Anna Durbin ₁ , Paul Pickrell ₁ , Eric S Daar ₁ , Larry Bush ₁ , Joel Solis ₁ , Quito Osuna Carr ₁ , Temitope Oyedele ₁ , Susan Buchbinder ₁ , Jessica Cowden ₁ , Sergio L Vargas ₁ , Alfredo Guerreros Benavides ₁ , Robert Call ₁ , Michael C Keefer ₁ , Beth D Kirkpatrick ₁ , John Pullman ₁ , Tina Tong ₁ , Margaret Brewinski Isaacs ₁ , David Benkeser ₁ , Holly E Janes ₁ , Martha C Nason ₁ , Justin A Green ₁ , Elizabeth J Kelly ₁ , Jill Maaske ₁ , Nancy Mueller ₁ , Kathryn Shoemaker ₁ , Therese Takas ₁ , Richard P Marshall ₁ , Menelas N Pangalos ₁ , Tonya Villafana ₁ , Antonio Gonzalez-Lopez ₁ ,

Affiliation

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.).

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.)

中文翻译：

AZD1222 (ChAdOx1 nCoV-19) Covid-19 疫苗的 3 期安全性和有效性

背景

在美国、智利和秘鲁，AZD1222 (ChAdOx1 nCoV-19) 疫苗在严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染风险较高的大量多样化人群中的安全性和有效性尚未得到证实。已知。

方法

在这项正在进行的双盲、随机、安慰剂对照 3 期临床试验中，我们研究了两剂 AZD1222 与安慰剂相比在预防 2019 年有症状和严重冠状病毒病发作方面的安全性、疫苗功效和免疫原性（ Covid-19）在美国、智利和秘鲁，成人（包括老年人）第二次接种后 15 天或更长时间。

结果

共有 32,451 名参与者以 2:1 的比例进行随机分组，接受 AZD1222（21,635 名参与者）或安慰剂（10,816 名参与者）。 AZD1222是安全的，严重和需要医疗处理的不良事件以及特别关注的不良事件的发生率较低；发生率与安慰剂组中观察到的相似。两组的局部和全身反应一般都是轻度或中度。 65 岁及以上参与者的总体估计疫苗效力为 74.0%（95% 置信区间 [CI]，65.3 至 80.5；P<0.001），估计疫苗效力为 83.5%（95% CI，54.2 至 94.1）。疫苗的高功效在一系列人口亚组中是一致的。在完全接种疫苗的分析亚组中，AZD1222组的17,662名参与者中没有观察到有严重或危重症状的Covid-19病例；安慰剂组的 8550 名参与者中有 8 例 (<0.1%)。预防 SARS-CoV-2 感染（核衣壳抗体血清转化）的估计疫苗功效为 64.3%（95% CI，56.1 至 71.0；P<0.001）。 SARS-CoV-2 刺突蛋白结合和中和抗体在第一次给药后增加，并在第二次给药后 28 天测量时进一步增加。