Abstract
This multicenter, double-blind, phase 2a part of a phase 2/3 study assessed the efficacy and safety of ensitrelvir, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease inhibitor, in Japanese patients with mild-to-moderate coronavirus disease 2019 (COVID-19) or asymptomatic SARS-CoV-2 infection. Sixty-nine patients were randomized (1:1:1) to orally receive 5-day ensitrelvir fumaric acid (375 mg on day 1 followed by 125 mg daily, or 750 mg on day 1 followed by 250 mg daily) or placebo and followed up until day 28. The primary outcome was the change from baseline in the SARS-CoV-2 viral titer. A total of 16, 14, and 17 patients in the ensitrelvir 125 mg, ensitrelvir 250 mg, and placebo groups, respectively, were included in the intention-to-treat population (mean age: 38.0 to 40.4 years). On day 4, the change from baseline in SARS-CoV-2 viral titer (log 10 50% tissue culture infectious dose/mL) in patients with positive viral titer and viral RNA at baseline was greater with ensitrelvir 125 mg (mean [standard deviation], -2.42 [1.42]; P = 0.0712) and 250 mg (-2.81 [1.21]; P = 0.0083) versus placebo (-1.54 [0.74]); ensitrelvir treatment reduced SARS-CoV-2 RNA by -1.4 to -1.5 log 10 copies/mL versus placebo. The viral titer and viral RNA were similar across groups on and after day 6. The median time to infectious viral clearance decreased by approximately 50 h with ensitrelvir treatment. All adverse events were mild to moderate. Ensitrelvir treatment demonstrated rapid SARS-CoV-2 clearance and was well tolerated (Japan Registry of Clinical Trials identifier: jRCT2031210350).
Keywords: COVID-19; Japanese; S-217622; SARS-CoV-2 3C-like protease inhibitor; ensitrelvir; proof-of-concept study; viral titer.
【저자키워드】 COVID-19, Japanese, viral titer., proof-of-concept study, ensitrelvir, SARS-CoV-2 3C-like protease inhibitor, S-217622, 【초록키워드】 Treatment, coronavirus disease, SARS-CoV-2, coronavirus, SARS-COV-2 infection, protease, viral clearance, Protease inhibitor, Randomized, Asymptomatic, Culture, clinical, Patient, Japan, Mild, Efficacy and safety, Placebo, SARS-CoV-2 RNA, Viral RNA, multicenter, registry, group, moderate, Mild-to-moderate, double-blind, acute respiratory syndrome, Primary outcome, tissue, median time, intention-to-treat population, positive, SARS-CoV-2 clearance, viral titer, SARS-CoV-2 viral, log, greater, reduced, demonstrated, groups, receive, All adverse event, baseline, fumaric acid, phase 2/3, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2, oral, novel, phase, Result, Part,