METHODS: This double-blind, randomized, placebo-controlled, phase 2 study examined the safety and efficacy of VIR-2482 for seasonal influenza A illness prevention in unvaccinated healthy adults. Participants (N = 2977) were randomized 1:1:1 to receive VIR-2482 450 mg, VIR-2482 1200 mg, or placebo via intramuscular (IM) injection. Primary and secondary efficacy endpoints were the proportions of participants with reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed influenza A infection and either protocol-defined influenza-like illness (ILI) and Centers for Disease Control and Prevention (CDC)-defined ILI or World Health Organization (WHO)-defined ILI, respectively.
RESULTS: VIR-2482 450 mg and 1200 mg prophylaxis did not reduce the risk of protocol-defined ILI with RT-PCR-confirmed influenza A versus placebo (relative risk reduction [RRR], 3.8% [95% CI: -67.3, 44.6] and 15.9% [95% CI: -49.3, 52.3], respectively). At the 1200 mg dose, the RRRs in influenza A illness were 57.2% [95% CI: -2.5, 82.2] using CDC-ILI and 44.1% [95% CI: -50.5, 79.3] using WHO-ILI definitions, respectively. Serum VIR-2482 levels were similar regardless of influenza status; variants with reduced VIR-2482 susceptibility were not detected. Local injection-site reactions were mild and similar across groups.
CONCLUSIONS: VIR-2482 1200 mg IM was well tolerated but did not significantly prevent protocol-defined ILI. Secondary endpoint analyses suggest this dose may have reduced influenza A illness.
方法:这种双盲,随机化,安慰剂对照,2期研究检查了VIR-2482在未接种疫苗的健康成人中预防季节性甲型流感的安全性和有效性.参与者(N=2977)被随机分为1:1:1,接受VIR-2482450mg,VIR-24821200毫克,或安慰剂通过肌内(IM)注射。主要和次要疗效终点是逆转录聚合酶链反应(RT-PCR)确认的甲型流感感染和方案定义的流感样疾病(ILI)以及疾病控制和预防中心(CDC)定义的ILI或世界卫生组织(WHO)定义的ILI的参与者比例。分别。
结果:VIR-2482450mg和1200mg预防并没有降低RT-PCR确认的甲型流感与安慰剂相比方案定义的ILI的风险(相对风险降低[RRR],3.8%[95%CI:-67.3,44.6]和15.9%[95%CI:-49.3,52.3],分别)。在1200毫克的剂量,使用CDC-ILI,甲型流感疾病的RRR为57.2%[95%CI:-2.5,82.2],使用WHO-ILI定义为44.1%[95%CI:-50.5,79.3],分别。无论流感状态如何,血清VIR-2482水平相似;未检测到具有降低的VIR-2482易感性的变体。局部注射部位反应温和,组间相似。
结论:VIR-24821200mgIM耐受性良好,但未明显预防方案定义的ILI。次要终点分析表明,该剂量可能减少了甲型流感疾病。