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