Efficacy and safety of SIM0417 (SSD8432) plus ritonavir for COVID-19 treatment: a randomised, double-blind, placebo-controlled, phase 1b trial

作者：Fuxiang Wang, Wen Hui Xiao, Yimin Tang, Mengli Cao, Dan Shu, Tetsuya Asakawa, Yechun Xu, Xiangrui Jiang, Leike Zhang, Wei Wang, Jianxing Tang, Yuansheng Huang, Yang Yang, Yumei Yang, Renhong Tang, Jingshan Shen, Hongzhou Lu · 发表于：The Lancet Regional Health - Western Pacific · 年份：2023 · DOI：10.1016/j.lanwpc.2023.100835 · 被引用次数：34 · 研究领域：SARS-CoV-2 and COVID-19 Research、Pharmacological Receptor Mechanisms and Effects、COVID-19 Clinical Research Studies

Background SIM0417 (SSD8432) is an orally administered coronavirus main proteinase (3CL pro ) inhibitor with potential anti-SARS-CoV-2 activity. This study aimed to evaluate the efficacy and safety of SIM0417 plus ritonavir (a pharmacokinetic enhancer) in adults with COVID-19. Methods This was a randomised, double-blind, placebo-controlled, phase 1b study in China. Adults with asymptomatic infection, mild or moderate COVID-19 were randomly assigned (3:3:2) to receive either 750 mg SIM0417 plus 100 mg ritonavir, 300 mg SIM0417 plus 100 mg ritonavir or placebo every 12 h for 10 doses. The main efficacy endpoints included SARS-CoV-2 viral load, proportion of participants with positive SARS-CoV-2 nucleic acid test and time to alleviation of COVID-19 symptoms. This trial is registered with ClinicalTrials.gov, NCT05369676. Findings Between May 12 and August 29, 2022, 32 participants were enrolled and randomised to high dose group (n = 12), low dose group (n = 12) or placebo (n = 8). The viral load change from baseline in high dose group was statistically lower compared with placebo, with a maximum mean difference of −2.16 ± 0.761 log 10 copies/mL (p = 0.0124) on Day 4. The proportion of positive SARS-CoV-2 in both active groups were lower than the placebo. The median time to sustained alleviation of COVID-19 symptoms was 2.0 days in high dose group versus 6.0 days in the placebo group (HR = 3.08, 95% CI 0.968–9.818). SIM0417 plus ritonavir were well tolerated with all adverse event...