一项II期随机双盲安慰剂对照研究，旨在评估新型广谱抗病毒药物HEX17在流感激发的受控人体感染模型中的疗效。
A Phase II, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of HEX17, a Novel Broad-Spectrum Antiviral Drug, in a Controlled Human Infection Model of Influenza Challenge.
作者信息
Kitson Geoff, Byford Marion, Cass Lindsey, Howat David, Köhn Brigitte, Bisquera Alessandra, Catchpole Andrew, Noulin Nicolas, Thomson Douglas
机构信息
Pneumagen Ltd., Kinburn Castle, Doubledykes Road, St Andrews, Fife, KY16 9DR, UK.
Exploristics Ltd., 24 Linenhall St, Belfast, BT2 8BG, UK.
出版信息
Infect Dis Ther. 2025 Jul 2. doi: 10.1007/s40121-025-01179-2.
INTRODUCTION
Viral respiratory tract infections are of global concern, with an unmet need for a broad-spectrum antiviral prophylactic. HEX17, a multivalent carbohydrate-binding module, binds to sialic acid, a cell surface glycan used by many viruses for host cell entry. HEX17 represents a potential broad-spectrum antiviral prophylactic therapy.
METHODS
This phase II randomised double-blind, placebo-controlled study was conducted in a UK centre. Healthy adults (18-55 years) were randomised (3:3:4) to daily HEX17 for 3 days (2.8 mg HEX17 from day - 3 to - 1); single-dose HEX17 (2.8 mg HEX17 on day - 3; placebo on day - 2 and - 1); or daily placebo (day - 3 to - 1). Participants were challenged with influenza virus on day 0 and assessed from days 1 to 8. Primary outcomes were incidence and severity of symptomatic influenza in the pooled HEX17 arms versus placebo, in the per protocol population (PPP). Safety analysis included all participants receiving at least one dose of HEX17/placebo.
RESULTS
Of 104 participants enrolled between August 2022 and March 2023, 99 were included in the PPP (single-dose HEX17, n = 29; daily HEX17, n = 30; placebo, n = 40). Symptomatic influenza occurred in 16/40 (40.0%) participants in the placebo arm versus 12/59 (20.3%) in the pooled HEX17 arms (- 19.7% decrease; 95% confidence interval [CI] - 38.0, - 1.3; p = 0.0331). The median peak total symptoms score was 3.00 in the placebo arm and 2.00 in the pooled HEX17 arms (versus placebo: 95% CI - 2.00, 0.00; p = 0.1427). Unsolicited adverse events (AEs) occurred in 17/41 (41.5%), 10/32 (31.3%), and 9/31 (29.0%) participants in placebo, daily HEX17, and single-dose HEX17 arms, respectively (safety population). No deaths or serious AEs occurred.
CONCLUSION
Prophylactic HEX17 reduced the incidence of symptomatic influenza infection and may protect at-risk patients against influenza infection.
TRIAL REGISTRATIONS
EudraCT 2022-001853-22, Clinicaltrials.gov NCT05507567.
引言
病毒性呼吸道感染是全球关注的问题，目前对广谱抗病毒预防药物仍有需求。HEX17是一种多价碳水化合物结合模块，可与唾液酸结合，唾液酸是许多病毒用于进入宿主细胞的细胞表面聚糖。HEX17代表了一种潜在的广谱抗病毒预防性治疗方法。
方法
这项II期随机双盲、安慰剂对照研究在英国一个中心进行。健康成年人（18 - 55岁）被随机分组（3:3:4），连续3天每日服用HEX17（从第-3天至-1天服用2.8毫克HEX17）；单剂量HEX17（第-3天服用2.8毫克HEX17；第-2天和-1天服用安慰剂）；或每日服用安慰剂（第-3天至-1天）。参与者在第0天用流感病毒进行攻击，并在第1天至8天进行评估。主要结局是在意向性分析人群中，合并的HEX17组与安慰剂组出现有症状流感的发生率和严重程度。安全性分析包括所有接受至少一剂HEX17/安慰剂的参与者。
结果
在2022年8月至2023年3月招募的104名参与者中，99名被纳入意向性分析人群（单剂量HEX17组，n = 29；每日HEX17组，n = 30；安慰剂组，n = 40）。安慰剂组16/40（40.0%）的参与者出现有症状流感，而合并的HEX17组为12/59（20.3%）（降低19.7%；95%置信区间[CI] - 38.0，- 1.3；p = 0.0331）。安慰剂组的症状总分峰值中位数为3.00，合并的HEX17组为2.00（与安慰剂相比：95% CI - 2.00，0.00；p = 0.1427）。安慰剂组、每日HEX17组和单剂量HEX17组分别有17/41（41.5%）、10/32（31.3%）和9/31（29.0%）的参与者出现非预期不良事件（安全性人群）。未发生死亡或严重不良事件。
结论
预防性使用HEX17可降低有症状流感感染的发生率，并可能保护高危患者免受流感感染。
试验注册号
EudraCT 2022 - 001853 - 22，Clinicaltrials.gov NCT05507567。
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