Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine.
Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine.
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DOI：
10.1056/nejmoa2105290
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发表时间：
2021-12-16
期刊：
影响因子：
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通讯作者：
AstraZeneca AZD1222 Clinical Study Group
中科院分区：
文献类型：
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作者：
Falsey AR;Sobieszczyk ME;Hirsch I;Sproule S;Robb ML;Corey L;Neuzil KM;Hahn W;Hunt J;Mulligan MJ;McEvoy C;DeJesus E;Hassman M;Little SJ;Pahud BA;Durbin A;Pickrell P;Daar ES;Bush L;Solis J;Carr QO;Oyedele T;Buchbinder S;Cowden J;Vargas SL;Guerreros Benavides A;Call R;Keefer MC;Kirkpatrick BD;Pullman J;Tong T;Brewinski Isaacs M;Benkeser D;Janes HE;Nason MC;Green JA;Kelly EJ;Maaske J;Mueller N;Shoemaker K;Takas T;Marshall RP;Pangalos MN;Villafana T;Gonzalez-Lopez A;AstraZeneca AZD1222 Clinical Study Group
AZD1222(ChAdOx1 nCoV-19)疫苗在美国、智利和秘鲁感染严重急性呼吸综合征冠状病毒2(SARS-CoV-2)风险增加的大型多样化人群中的安全性和有效性尚不清楚。在这项正在进行的双盲、随机、安慰剂对照的3期临床试验中，我们研究了两剂AZD1222与安慰剂在美国、智利和秘鲁预防2019年有症状和严重冠状病毒病(新冠肺炎)15天或更长时间的发病的安全性、疫苗有效性和免疫原性。共有32,451名参与者按2：1的比例随机接受AZD1222(21,635名参与者)或安慰剂(10,816名参与者)的治疗。AZD1222是安全的，严重和医疗护理的不良事件以及特别关注的不良事件的发生率很低；这些发生率与安慰剂组观察到的相似。在两组患者中，应征的局部和全身反应一般为轻度或中度。在65岁或以上的参与者中，总体估计疫苗效力为74.0%(95%可信区间为65.3%至80.5%；P<；0.001)，估计疫苗效力为83.5%(95%可信区间为54.2%至94.1%)。疫苗的高效力在一系列人口统计亚组中是一致的。在完全接种分析亚组中，在AZD1222组的17,662名参与者中没有观察到严重或严重症状的新冠肺炎病例；在安慰剂组的8,550名参与者中观察到8例病例(<；0.1%)。预防SARS-CoV-2感染(核衣壳抗体血清转换)的疫苗效果估计为64.3%(95%CI，56.1to71.0；P<；0.001)。SARS-CoV-2刺突蛋白结合抗体和中和抗体在第一次接种后增加，在第二次接种后28天进一步增加。AZD1222在包括老年人在内的不同人群中预防有症状和严重的新冠肺炎是安全有效的。(由阿斯利康等公司资助；ClinicalTrials.gov编号，NCT04516746。)
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. 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. 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. 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.)