流感帽依赖性内切酶抑制剂 ZX-7101A 对无并发症流感成人患者的疗效和安全性:随机、双盲、安慰剂对照的 2/3 期试验。

IF 10.9 1区 医学 Q1 INFECTIOUS DISEASES
Hongyu Wang, Gang Wang, Yan Gao, Lihong Qu, Hong Wang, Min Deng, Hainv Gao, Yilin Li, Nan Yang, Baogui Wang, Rongge Liu, Xuzhu Ma, Zhen Tao, Guoqiang Zhang, Qian Wang, Weifeng Zhao, Yunsong Yu, Lin Chen, Lianchun Liang, Shengyu Wang, Lei Shao, Tao Yang, Jinglei Cao, Yuan Cao, Xiaoli Qin, Jingwen Ai, Huadong Zhu, Wenhong Zhang
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引用次数: 0

摘要

目的评估流感病毒帽依赖性内切酶抑制剂 ZX-7101A 在无并发症流感成人患者中的疗效和安全性,并探索治疗中出现的耐药性:我们在成人无并发症流感患者中开展了一项随机、双盲、安慰剂对照、适应性设计的 2 期和 3 期研究(ZX-7101A-202)。符合条件的患者按照体重和基线综合症状评分,以1:1:1的比例随机接受单剂量40或80毫克ZX-7101A或安慰剂。主要疗效终点是意向治疗感染者(ITTI)的流感症状缓解时间(TTAS):2期试验表明,与安慰剂相比,ZX-7101A的TTAS明显缩短:40或80毫克ZX-7101A的中位TTAS分别为34.7小时(95%置信区间[CI],22.8-43.4;p=0.005)和45.8小时(95%CI,32.0-66.3;p=0.020),而安慰剂组为63.6小时(95%CI,43.9-93.4)。在3期试验中,与安慰剂相比,ZX-7101A两个剂量组的TTAS均显著缩短:40毫克组的中位TTAS缩短至48.4小时(95%CI,40.5-55.6),80毫克组缩短至39.4小时(95%CI,35.8-49.3),而安慰剂组为62.9小时(95%CI,56.4-69.3)(p=0.003和p结论:ZX-7101A单次剂量为40毫克或80毫克,与安慰剂相比,能更快地缓解流感症状,是治疗流感的有效药物。单剂量治疗 ZX-7101A 未发现安全问题。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Efficacy and safety of ZX-7101A, an inhibitor of influenza cap-dependent endonuclease, in adults with uncomplicated influenza: a randomized, double-blind, placebo-controlled phase 2/3 trial.

Objectives: To evaluate the efficacy and safety of ZX-7101A: an inhibitor of influenza viral cap-dependent endonuclease, in adults with uncomplicated influenza and explore treatment-emergent resistance.

Methods: We conducted a randomized, double-blind, placebo-controlled, adaptive-design phase 2 and phase 3 studies (ZX-7101A-202) in adults with uncomplicated influenza. Eligible patients were randomized 1:1:1 to receive a single dose of 40 or 80 mg ZX-7101A or placebo, stratified by body weight and baseline composite symptom score. The primary efficacy endpoint was time to alleviation of influenza symptoms (TTAS) in intention-to-treat infected population.

Results: The phase 2 trial suggested significantly shorter TTAS for ZX-7101A compared with placebo: the median TTAS of 40 or 80 mg ZX-7101A groups were 34.7 hours (95% CI, 22.8-43.4; p 0.005) and 45.8 hours (95% CI, 32.0-66.3; p 0.020), compared with 63.6 hours (95% CI, 43.9-93.4) in the placebo group. In the phase 3 trial, the TTAS of both ZX-7101A dose groups was significantly shortened relative to the that of placebo group: the median TTAS was shortened to 48.4 hours (95% CI, 40.5-55.6) for 40 mg group and 39.4 hours (95% CI, 35.8-49.3) for 80 mg group, compared with 62.9 hours (95% CI, 56.4-69.3) for placebo group (p 0.003 and p < 0.001, respectively). In the safety population, ZX-7101A treatment was associated with fewer adverse events, with 41.8% (100/239) in the 40 mg group, 44.2% (106/240) in the 80 mg group, and 53.8% (129/240) in the placebo group. The majority of adverse events were mild or moderate. Emergence of resistance to ZX-7101A through I38T amino acid substitution was detected in 5/278 (1.8%) patients.

Discussion: ZX-7101A was an effective treatment for influenza with a single dose of either 40 mg or 80 mg, with more rapid alleviation of influenza symptoms vs. placebo. No safety concerns were identified with single dose treatment of ZX-7101A.

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来源期刊
CiteScore
25.30
自引率
2.10%
发文量
441
审稿时长
2-4 weeks
期刊介绍: Clinical Microbiology and Infection (CMI) is a monthly journal published by the European Society of Clinical Microbiology and Infectious Diseases. It focuses on peer-reviewed papers covering basic and applied research in microbiology, infectious diseases, virology, parasitology, immunology, and epidemiology as they relate to therapy and diagnostics.
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