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

• Published in: The Lancet regional health. Western Pacific 2023-09, Vol.38, p.100835
• Main Authors: Fuxiang Wang, Wen 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
• Format: Article
• Language: English
• Subjects: 3CL protease inhibitor; Alleviation of COVID-19 symptoms; Covid-19; SARS-CoV-2 viral load
• ISSN: 2666-6065; 2666-6065

Background: SIM0417 (SSD8432) is an orally administered coronavirus main proteinase (3CLpro) 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 log10 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 events in grade 1. Interpretation: SIM0417 plus ritonavir was generally well tolerated. The efficacy of SIM0417 showed a monotonic dose–response relationship, and the 750 mg SIM0417 plus 100 mg ritonavir was selected as the recommended clinical dose. Funding: The study was funded by Jiangsu Simcere Pharmaceutical Co., Ltd.