Abstract：
BACKGROUND: Influenza A results in significant morbidity and mortality. VIR-2482, an engineered human monoclonal antibody with extended half-life, targets a highly conserved epitope on the stem region of influenza A hemagglutinin, and may protect against seasonal and pandemic influenza.
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.
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.
摘要：
背景：甲型流感导致显著的发病率和死亡率。VIR-2482，一种半衰期延长的工程化人类单克隆抗体，靶向甲型流感血凝素茎区高度保守的表位，并可能预防季节性和大流行性流感。
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。
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。
