Wang Yeming, Shang Lianhan, Wu Lei, Wang Xia, Ding Banghan, Hu Ke, He Yingli, Li Guangming, Zhai Jie, Hu Junyan, Tian Yingping, Wang Jun, Yan Li, Liu Bin, Song Gengshen, He Yuxian, Wang Chen, Cao Bin
National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; New Cornerstone Science Laboratory; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
Hebei Province Hospital of Traditional Chinese Medicine, Shijiazhuang, China.
Nat Commun. 2025 Aug 7;16(1):7272. doi: 10.1038/s41467-025-62214-x.
YKYY017 is a SARS-CoV-2 membrane fusion inhibitor. We report efficacy and safety of inhaled YKYY017 for COVID-19 patients with mild to moderate illness from a phase 2 trial (ChiCTR2300075467). 239 patients aged 18-75 years with mostly mild COVID-19 were randomly allocated to receive aerosol inhalation of 10 or 20 mg YKYY017 or placebo once daily. The primary endpoint is the change in SARS-CoV-2 viral load from baseline to Day 4. The mean (±SE) differences in viral load change from baseline were -0.48 ± 0.27 log copies/mL (95% CI, -1.01 to 0.06) for the 20 mg group and -0.27 ± 0.27 log copies/mL (95% CI, -0.79 to 0.26) for the 10 mg group, compared to the placebo group. Viral load changes at visits other than Day 4 did not differ significantly from placebo in either the 10 or 20 mg YKYY017 groups. The time to sustained symptom recovery was shorter in the 20 mg YKYY017 group (median 117.53, 95%CI 95.33 to 141.45 hours) than in the placebo group (median 143.00, 95%CI 139.17 to 186.87 hours; HR 1.552, 95%CI 1.089 to 2.214, p = 0.0151), whereas the 10 mg YKYY017 group showed a similar but not statistically significant trend compared to placebo (p = 0.0833). The time to sustained symptom alleviation was shorter in both the 20 and 10 mg YKYY017 groups than in the placebo group. The adverse events were mostly mild to moderate. The primary outcome was not met. Following a supplementary phase 1b trial, we are planning another phase 2/3 trial using a twice-daily 20 mg YKYY017 regimen to further assess efficacy and safety.
YKYY017是一种新型冠状病毒膜融合抑制剂。我们报告了一项2期试验（ChiCTR2300075467）中吸入式YKYY017治疗轻至中度新冠肺炎患者的疗效和安全性。239名年龄在18至75岁之间、大多为轻度新冠肺炎的患者被随机分配，每天接受一次10毫克或20毫克YKYY017或安慰剂的雾化吸入。主要终点是从基线到第4天新型冠状病毒病毒载量的变化。与安慰剂组相比，20毫克组病毒载量较基线变化的均值（±标准误）为-0.48±0.27 log拷贝/毫升（95%置信区间，-1.01至0.06），10毫克组为-0.27±0.27 log拷贝/毫升（95%置信区间，-0.79至0.26）。在第4天之外的其他访视中，10毫克或20毫克YKYY017组的病毒载量变化与安慰剂组相比均无显著差异。20毫克YKYY017组持续症状恢复时间（中位数117.53，95%置信区间95.33至141.45小时）比安慰剂组（中位数143.00，95%置信区间139.17至186.87小时；风险比1.552，95%置信区间1.089至2.214，p = 0.0151）短，而10毫克YKYY017组与安慰剂组相比显示出相似但无统计学意义的趋势（p = 0.0833）。20毫克和10毫克YKYY017组持续症状缓解时间均比安慰剂组短。不良事件大多为轻至中度。主要结局未达到。在一项补充1b期试验之后，我们正计划开展另一项2/3期试验，采用每日两次20毫克YKYY017方案，以进一步评估疗效和安全性。
