Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19.
Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19.
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DOI：
10.1056/nejmoa2116620
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发表时间：
2022-06-09
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单克隆抗体组合AZD 7442由tixagevimab和cigavimab组成，这两种针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的中和抗体具有延长的半衰期，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，AZD 7442具有约90天的延长半衰期。在一项正在进行的III期试验中，我们招募了对2019年冠状病毒病（Covid-19）疫苗接种反应不充分风险增加、暴露于SARS-CoV-2风险增加或两者兼而有之的成年人（≥18岁）。参与者以2：1的比例随机分配接受单次剂量（连续两次肌内注射，一次含有tixagevimab，另一次含有cigavimab）300 mg AZD 7442或生理盐水安慰剂，在主要分析中随访长达183天。主要安全性终点是AZD 7442单次给药后不良事件的发生率。主要疗效终点为AZD 7442或安慰剂给药后第183天或之前出现的症状性Covid-19（通过逆转录酶聚合酶链反应试验确认的SARS-CoV-2感染）。共有5197名参与者接受了随机分组，并接受了一剂AZD 7442或安慰剂（AZD 7442组3460名，安慰剂组1737名）。在30%的参与者知道他们的随机分配后进行主要分析。总体而言，AZD 7442组3461例受试者中有1221例（35.3%）和安慰剂组1736例受试者中有593例（34.2%）报告至少发生1起不良事件，其中大多数严重程度为轻度或中度。3441名参与者中有8人出现了新冠肺炎症状AZD 7442组和1731例受试者中的17例（0.2%）（1.0%），安慰剂组（相对危险度降低，76.7%; 95%可信区间[CI]，46.0 - 90.0; P<0.001）;中位6个月的延长随访显示相对风险降低82.8%（95%CI，65.8 - 91.4）。发生了5例重度或危重新型冠状病毒肺炎病例和2例新型冠状病毒肺炎相关死亡病例，均发生在安慰剂组。AZD 7442单次给药可有效预防Covid-19，无明显安全性问题。（由阿斯利康和美国政府资助; PROVENT ClinicalTrials.gov编号，NCT 04625725。
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. 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. 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. 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.)