1区 · 医学
Article
作者: Xu, Yechun ; Shen, Yinzhong ; Wang, Fuxiang ; Lin, Ling ; Cao, Bin ; Liu, Chenfan ; Ye, Xianwei ; Liu, Yihe ; Zhou, Hourong ; Lu, Hongzhou ; Xu, Jiuyang ; Yi, Zhennan ; Fan, Jia ; Wang, Chunying ; Tang, Renhong ; Chen, Zhu ; Shen, Jingshan ; Jiang, Rongmeng ; Gong, Fengyun ; Gu, Xiaoying ; Yao, Xiangyang ; Hu, Bijie ; Yang, Yumei ; Hu, Honglin ; Shang, Lianhan ; Cheng, Cong ; Wang, Chen ; Zhang, Leike ; Peng, Ping ; Wang, Yeming ; Huang, Chaolin
BACKGROUND:Simnotrelvir is an oral 3-chymotrypsin-like protease inhibitor that has been found to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy in a phase 1B trial.
METHODS:In this phase 2-3, double-blind, randomized, placebo-controlled trial, we assigned patients who had mild-to-moderate coronavirus disease 2019 (Covid-19) and onset of symptoms within the past 3 days in a 1:1 ratio to receive 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days. The primary efficacy end point was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19-related symptoms for 2 consecutive days. Safety and changes in viral load were also assessed.
RESULTS:A total of 1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir and 605 to receive placebo. Among patients in the modified intention-to-treat population who received the first dose of trial drug or placebo within 72 hours after symptom onset, the time to sustained resolution of Covid-19 symptoms was significantly shorter in the simnotrelvir group than in the placebo group (180.1 hours [95% confidence interval {CI}, 162.1 to 201.6] vs. 216.0 hours [95% CI, 203.4 to 228.1]; median difference, -35.8 hours [95% CI, -60.1 to -12.4]; P = 0.006 by Peto-Prentice test). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group (mean difference [±SE], -1.51±0.14 log10 copies per milliliter; 95% CI, -1.79 to -1.24). The incidence of adverse events during treatment was higher in the simnotrelvir group than in the placebo group (29.0% vs. 21.6%). Most adverse events were mild or moderate.
CONCLUSIONS:Early administration of simnotrelvir plus ritonavir shortened the time to the resolution of symptoms among adult patients with Covid-19, without evident safety concerns. (Funded by Jiangsu Simcere Pharmaceutical; ClinicalTrials.gov number, NCT05506176.).