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Intramuscular AZD7442 (Tixagevimab–Cilgavimab) for Prevention of Covid-19
The New England Journal of Medicine ( IF 158.5 ) Pub Date : 2022-04-20 , DOI: 10.1056/nejmoa2116620
Myron J Levin 1 , Andrew Ustianowski 1 , Stéphane De Wit 1 , Odile Launay 1 , Miles Avila 1 , Alison Templeton 1 , Yuan Yuan 1 , Seth Seegobin 1 , Adam Ellery 1 , Dennis J Levinson 1 , Philip Ambery 1 , Rosalinda H Arends 1 , Rohini Beavon 1 , Kanika Dey 1 , Pedro Garbes 1 , Elizabeth J Kelly 1 , Gavin C K W Koh 1 , Karen A Near 1 , Kelly W Padilla 1 , Konstantina Psachoulia 1 , Audrey Sharbaugh 1 , Katie Streicher 1 , Menelas N Pangalos 1 , Mark T Esser 1 ,
Affiliation  

Background

The monoclonal-antibody combination AZD7442 is composed of tixagevimab and cilgavimab, two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that have an extended half-life and have been shown to have prophylactic and therapeutic effects in animal models. Pharmacokinetic data in humans indicate that AZD7442 has an extended half-life of approximately 90 days.

Methods

In an ongoing phase 3 trial, we enrolled adults (≥18 years of age) who had an increased risk of an inadequate response to vaccination against coronavirus disease 2019 (Covid-19), an increased risk of exposure to SARS-CoV-2, or both. Participants were randomly assigned in a 2:1 ratio to receive a single dose (two consecutive intramuscular injections, one containing tixagevimab and the other containing cilgavimab) of either 300 mg of AZD7442 or saline placebo, and they were followed for up to 183 days in the primary analysis. The primary safety end point was the incidence of adverse events after a single dose of AZD7442. The primary efficacy end point was symptomatic Covid-19 (SARS-CoV-2 infection confirmed by means of reverse-transcriptase–polymerase-chain-reaction assay) occurring after administration of AZD7442 or placebo and on or before day 183.

Results

A total of 5197 participants underwent randomization and received one dose of AZD7442 or placebo (3460 in the AZD7442 group and 1737 in the placebo group). The primary analysis was conducted after 30% of the participants had become aware of their randomized assignment. In total, 1221 of 3461 participants (35.3%) in the AZD7442 group and 593 of 1736 participants (34.2%) in the placebo group reported having at least one adverse event, most of which were mild or moderate in severity. Symptomatic Covid-19 occurred in 8 of 3441 participants (0.2%) in the AZD7442 group and in 17 of 1731 participants (1.0%) in the placebo group (relative risk reduction, 76.7%; 95% confidence interval [CI], 46.0 to 90.0; P<0.001); extended follow-up at a median of 6 months showed a relative risk reduction of 82.8% (95% CI, 65.8 to 91.4). Five cases of severe or critical Covid-19 and two Covid-19–related deaths occurred, all in the placebo group.

Conclusions

A single dose of AZD7442 had efficacy for the prevention of Covid-19, without evident safety concerns. (Funded by AstraZeneca and the U.S. government; PROVENT ClinicalTrials.gov number, NCT04625725.)



中文翻译:

肌肉注射 AZD7442(Tixagevimab-Cilgavimab)用于预防 Covid-19

背景

单克隆抗体组合 AZD7442 由 tixagevimab 和 cilgavimab 组成,这两种针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的中和抗体具有较长的半衰期,并已在动物模型中显示出预防和治疗作用。人体药代动力学数据表明 AZD7442 的半衰期延长至约 90 天。

方法

在一项正在进行的 3 期试验中,我们招募了对 2019 年冠状病毒病 (Covid-19) 疫苗接种反应不足的风险增加、暴露于 SARS-CoV-2 的风险增加的成年人(≥18 岁),或两者。参与者以 2:1 的比例随机分配接受单剂量(连续两次肌内注射,一次含有 tixagevimab,另一次含有 cilgavimab)300 mg AZD7442 或生理盐水安慰剂,并对他们进行长达 183 天的随访。初步分析。主要安全终点是单剂量 AZD7442 后不良事件的发生率。主要疗效终点是在服用 AZD7442 或安慰剂后以及第 183 天或之前发生的有症状的 Covid-19(通过逆转录酶聚合酶链反应测定证实的 SARS-CoV-2 感染)。

结果

共有 5197 名参与者接受了随机分组,并接受一剂 AZD7442 或安慰剂(AZD7442 组 3460 名,安慰剂组 1737 名)。主要分析是在 30% 的参与者了解他们的随机分配情况后进行的。总体而言,AZD7442 组 3461 名参与者中的 1221 名参与者(35.3%)和安慰剂组 1736 名参与者中的 593 名参与者(34.2%)报告至少出现一种不良事件,其中大多数为轻度或中度严重程度。AZD7442 组 3441 名参与者中有 8 名 (0.2%) 出现 Covid-19 症状,安慰剂组 1731 名参与者中有 17 名 (1.0%) 出现症状(相对风险降低,76.7%;95% 置信区间 [CI],46.0 至90.0;P<0.001);中位 6 个月的延长随访显示相对风险降低了 82.8%(95% CI,65.8 至 91.4)。安慰剂组发生了 5 例严重或危重 Covid-19 病例以及 2 例与 Covid-19 相关的死亡病例。

结论

单剂量的 AZD7442 可有效预防 Covid-19,且没有明显的安全问题。(由阿斯利康和美国政府资助;PROVENT ClinicalTrials.gov 编号,NCT04625725。)

更新日期:2022-04-21
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