The Lancet Regional Health. Western Pacific (Sep 2023)

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

  • 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

Journal volume & issue
Vol. 38
p. 100835

Abstract

Read online

Summary: 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.

Keywords