A Randomized, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of VIR-2482 in Healthy Adults for Prevention of Influenza A Illness (PENINSULA).

IF 8.2 1区 医学 Q1 IMMUNOLOGY
Susanna K Tan, Deborah Cebrik, David Plotnik, Maria L Agostini, Keith Boundy, Christy M Hebner, Wendy W Yeh, Phillip S Pang, Jaynier Moya, Charles Fogarty, Manuchehr Darani, Frederick G Hayden
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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 injection. Primary and secondary efficacy endpoints were the proportions of participants with reverse transcriptase-polymerase chain reaction-confirmed influenza A infection and either protocol-defined influenza-like illness (ILI) and Centers for Disease Control and Prevention-defined ILI or World Health Organization-defined ILI, respectively.

Results: VIR-2482 450 mg and 1200 mg prophylaxis did not reduce the risk of protocol-defined ILI with reverse transcriptase-polymerase chain reaction-confirmed influenza A versus placebo (relative risk reduction, 3.8% [95% confidence interval (CI), -67.3 to 44.6] and 15.9% [95% CI, -49.3 to 52.3], respectively). At the 1200-mg dose, the relative risk reductions in influenza A illness were 57.2% (95% CI: -2.5 to 82.2) using Centers for Disease Control and Prevention ILI and 44.1% (95% CI: -50.5 to 79.3) using World Health Organization 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 intramuscular was well tolerated but did not significantly prevent protocol-defined ILI. Secondary endpoint analyses suggest this dose may have reduced influenza A illness. Trial registration: ClinicalTrials.gov identifier, NCT05567783.

评估 VIR-2482 在健康成人中预防甲型流感的安全性和有效性的随机安慰剂对照试验 (PENINSULA)。
背景:甲型流感导致严重的发病率和死亡率。VIR-2482是一种具有延长半衰期的工程化人类单克隆抗体,以甲型流感血凝素茎区的高度保守表位为靶点,可预防季节性流感和大流行性流感:这项双盲、随机、安慰剂对照的 2 期研究考察了 VIR-2482 对未接种疫苗的健康成年人预防季节性甲型流感的安全性和有效性。参与者(N = 2977)按 1:1:1 的比例随机接受 VIR-2482 450 毫克、VIR-2482 1200 毫克或安慰剂肌肉注射。主要和次要疗效终点分别为经逆转录酶聚合酶链反应(RT-PCR)证实的甲型流感感染者比例,以及方案定义的流感样病症(ILI)和美国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:与安慰剂相比,450毫克和1200毫克VIR-2482预防剂并未降低RT-PCR确诊甲型流感协议定义的ILI风险(相对风险降低率[RRR]分别为3.8%[95% CI:-67.3,44.6]和15.9%[95% CI:-49.3,52.3])。根据 CDC-ILI 和 WHO-ILI 的定义,1200 毫克剂量的甲型流感发病率分别为 57.2% [95% CI:-2.5, 82.2]和 44.1% [95% CI:-50.5, 79.3]。无论流感状况如何,血清 VIR-2482 水平相似;未检测到对 VIR-2482 敏感性降低的变种。各组的局部注射部位反应轻微且相似:结论:VIR-2482 1200 毫克 IM 的耐受性良好,但不能显著预防方案定义的 ILI。次要终点分析表明,该剂量可能会减少甲型流感的发病率。
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来源期刊
Clinical Infectious Diseases
Clinical Infectious Diseases 医学-传染病学
CiteScore
25.00
自引率
2.50%
发文量
900
审稿时长
3 months
期刊介绍: Clinical Infectious Diseases (CID) is dedicated to publishing original research, reviews, guidelines, and perspectives with the potential to reshape clinical practice, providing clinicians with valuable insights for patient care. CID comprehensively addresses the clinical presentation, diagnosis, treatment, and prevention of a wide spectrum of infectious diseases. The journal places a high priority on the assessment of current and innovative treatments, microbiology, immunology, and policies, ensuring relevance to patient care in its commitment to advancing the field of infectious diseases.
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