Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.-猫眼课题宝

DOI：

10.1016/s0140-6736(20)32661-1

发表时间：

2021-01-09

期刊：

Lancet (London, England)

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

Voysey M;Clemens SAC;Madhi SA;Weckx LY;Folegatti PM;Aley PK;Angus B;Baillie VL;Barnabas SL;Bhorat QE;Bibi S;Briner C;Cicconi P;Collins AM;Colin-Jones R;Cutland CL;Darton TC;Dheda K;Duncan CJA;Emary KRW;Ewer KJ;Fairlie L;Faust SN;Feng S;Ferreira DM;Finn A;Goodman AL;Green CM;Green CA;Heath PT;Hill C;Hill H;Hirsch I;Hodgson SHC;Izu A;Jackson S;Jenkin D;Joe CCD;Kerridge S;Koen A;Kwatra G;Lazarus R;Lawrie AM;Lelliott A;Libri V;Lillie PJ;Mallory R;Mendes AVA;Milan EP;Minassian AM;McGregor A;Morrison H;Mujadidi YF;Nana A;O'Reilly PJ;Padayachee SD;Pittella A;Plested E;Pollock KM;Ramasamy MN;Rhead S;Schwarzbold AV;Singh N;Smith A;Song R;Snape MD;Sprinz E;Sutherland RK;Tarrant R;Thomson EC;Török ME;Toshner M;Turner DPJ;Vekemans J;Villafana TL;Watson MEE;Williams CJ;Douglas AD;Hill AVS;Lambe T;Gilbert SC;Pollard AJ;Oxford COVID Vaccine Trial Group

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723445/

如果部署一种安全有效的针对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的疫苗，覆盖率高，可能有助于控制新冠肺炎大流行。我们在对四项试验进行的合并中期分析中评估了ChAdOx1 nCoV-19疫苗的安全性和有效性。这项分析包括在英国、巴西和南非进行的四项正在进行的盲法、随机、对照试验的数据。18岁及以上的受试者被随机分配(1：1)接种ChAdOx1 nCoV-19疫苗或对照组(脑膜炎球菌A、C、W和Y组结合疫苗或生理盐水)。ChAdOx1nCoV-19组的参与者接受了两剂含有5 × 1010病毒颗粒的疫苗(标准剂量；SD/SD队列)；英国试验的一个子组接受了一半剂量作为他们的第一剂(低剂量)，以及一剂标准剂量作为他们的第二剂(LD/SD队列)。初步疗效分析包括第二次接种疫苗后14天以上血清扩增试验拭子阳性的血清阴性参与者出现症状新冠肺炎。参与者根据接受的治疗进行了分析，数据截止日期为2020年11月4日。疫苗效力计算为根据年龄调整的稳健泊松回归模型得出的1 - 相对风险。这项研究在ISRCTN89951424和ClinicalTrials.gov，NCT04324606，NCT04400838和NCT04444674上注册。在2020年4月23日至11月4日期间，23名 848名参与者和11名 636名参与者(英国7,548名，巴西4,088名)被纳入临时初级疗效分析。在接受两次标准剂量接种的参与者中，疫苗有效率为62.1%(95%可信区间41·0-75.7；ChAdOx1 nCoV-19组4440人中的27人[0.6%]，对照组为4455人中的71人[1.6%])；在接受低剂量后再接受标准剂量的参与者中，有效率为90.0%(67·4-97.0；1367人中的三人[0.2%]对1374人中的30人[2.2%]；pinteraction=0.010)。两组疫苗总有效率为70.4%(95·8%可信区间54·8-80·6；5807中30[0.5%]对5829中101[1.7%])。从第一剂服药后21天开始，共有10例新冠肺炎患者住院，均在对照组；2例被归类为重症新冠肺炎，包括1例死亡。共有74个 341个人月的安全随访(中位数为3.4个月，IQR1·3~4·8)：168名受试者发生175起严重不良事件，CHAdOx1nCoV19组发生84起，对照组发生91起。有三起事件被归类为可能与疫苗有关：一起发生在ChAdOx1 nCoV-19组，一起发生在对照组，另一起发生在一名参与者身上，该参与者仍被蒙面接受分组分配。ChAdOx1nCoV-19具有可接受的安全性，并在正在进行的临床试验的中期分析中被发现对有症状的新冠肺炎有效。英国研究与创新研究所、国家卫生研究院(NIHR)、防疫创新联盟、比尔和梅林达·盖茨基金会、莱曼基金会、Rede D‘Or、Brava和Telle基金会、NIHR牛津生物医学研究中心、泰晤士河谷和南米德兰的NIHR临床研究网络，以及阿斯利康。

A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D’Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

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