tetano
Editor, Senior Moderator
Lancet Reg Health West Pac
. 2023 Jul 11;38:100835.
doi: 10.1016/j.lanwpc.2023.100835. eCollection 2023 Sep. Efficacy and safety of SIM0417 (SSD8432) plus ritonavir for COVID-19 treatment: a randomised, double-blind, placebo-controlled, phase 1b trial
Fuxiang Wang[SUP] 1 [/SUP], Wen Xiao[SUP] 1 [/SUP], Yimin Tang[SUP] 1 [/SUP], Mengli Cao[SUP] 1 [/SUP], Dan Shu[SUP] 1 [/SUP], Tetsuya Asakawa[SUP] 2 [/SUP], Yechun Xu[SUP] 3 [/SUP], Xiangrui Jiang[SUP] 3 [/SUP], Leike Zhang[SUP] 4 [/SUP], Wei Wang[SUP] 5 [/SUP], Jianxing Tang[SUP] 5 [/SUP], Yuansheng Huang[SUP] 5 [/SUP], Yang Yang[SUP] 5 [/SUP], Yumei Yang[SUP] 5 [/SUP], Renhong Tang[SUP] 5 6 [/SUP], Jingshan Shen[SUP] 3 [/SUP], Hongzhou Lu[SUP] 1 [/SUP]
Affiliations
Background: SIM0417 (SSD8432) is an orally administered coronavirus main proteinase (3CL[SUP]pro[/SUP]) 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[SUB]10[/SUB] 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: 3CL protease inhibitor; Alleviation of COVID-19 symptoms; Covid-19; SARS-CoV-2 viral load.
. 2023 Jul 11;38:100835.
doi: 10.1016/j.lanwpc.2023.100835. eCollection 2023 Sep. Efficacy and safety of SIM0417 (SSD8432) plus ritonavir for COVID-19 treatment: a randomised, double-blind, placebo-controlled, phase 1b trial
Fuxiang Wang[SUP] 1 [/SUP], Wen Xiao[SUP] 1 [/SUP], Yimin Tang[SUP] 1 [/SUP], Mengli Cao[SUP] 1 [/SUP], Dan Shu[SUP] 1 [/SUP], Tetsuya Asakawa[SUP] 2 [/SUP], Yechun Xu[SUP] 3 [/SUP], Xiangrui Jiang[SUP] 3 [/SUP], Leike Zhang[SUP] 4 [/SUP], Wei Wang[SUP] 5 [/SUP], Jianxing Tang[SUP] 5 [/SUP], Yuansheng Huang[SUP] 5 [/SUP], Yang Yang[SUP] 5 [/SUP], Yumei Yang[SUP] 5 [/SUP], Renhong Tang[SUP] 5 6 [/SUP], Jingshan Shen[SUP] 3 [/SUP], Hongzhou Lu[SUP] 1 [/SUP]
Affiliations
- PMID: 37484496
- PMCID: PMC10362366
- DOI: 10.1016/j.lanwpc.2023.100835
Background: SIM0417 (SSD8432) is an orally administered coronavirus main proteinase (3CL[SUP]pro[/SUP]) 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[SUB]10[/SUB] 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: 3CL protease inhibitor; Alleviation of COVID-19 symptoms; Covid-19; SARS-CoV-2 viral load.