tetano
Editor, Senior Moderator
Antimicrob Agents Chemother
. 2022 Sep 13;e0069722.
doi: 10.1128/aac.00697-22. Online ahead of print.
A Randomized Phase 2/3 Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-Like Protease Inhibitor, in Japanese Patients with Mild-to-Moderate COVID-19 or Asymptomatic SARS-CoV-2 Infection: Results of the Phase 2a Part
Hiroshi Mukae[SUP] 1 [/SUP], Hiroshi Yotsuyanagi[SUP] 2 [/SUP], Norio Ohmagari[SUP] 3 [/SUP], Yohei Doi[SUP] 4 5 [/SUP], Takumi Imamura[SUP] 6 [/SUP], Takuhiro Sonoyama[SUP] 6 [/SUP], Takahiro Fukuhara[SUP] 6 [/SUP], Genki Ichihashi[SUP] 6 [/SUP], Takao Sanaki[SUP] 7 [/SUP], Keiko Baba[SUP] 7 [/SUP], Yosuke Takeda[SUP] 6 [/SUP], Yuko Tsuge[SUP] 6 [/SUP], Takeki Uehara[SUP] 6 [/SUP]
Affiliations
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[SUB]10[/SUB] 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[SUB]10[/SUB] 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.
. 2022 Sep 13;e0069722.
doi: 10.1128/aac.00697-22. Online ahead of print.
A Randomized Phase 2/3 Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-Like Protease Inhibitor, in Japanese Patients with Mild-to-Moderate COVID-19 or Asymptomatic SARS-CoV-2 Infection: Results of the Phase 2a Part
Hiroshi Mukae[SUP] 1 [/SUP], Hiroshi Yotsuyanagi[SUP] 2 [/SUP], Norio Ohmagari[SUP] 3 [/SUP], Yohei Doi[SUP] 4 5 [/SUP], Takumi Imamura[SUP] 6 [/SUP], Takuhiro Sonoyama[SUP] 6 [/SUP], Takahiro Fukuhara[SUP] 6 [/SUP], Genki Ichihashi[SUP] 6 [/SUP], Takao Sanaki[SUP] 7 [/SUP], Keiko Baba[SUP] 7 [/SUP], Yosuke Takeda[SUP] 6 [/SUP], Yuko Tsuge[SUP] 6 [/SUP], Takeki Uehara[SUP] 6 [/SUP]
Affiliations
- PMID: 36098519
- DOI: 10.1128/aac.00697-22
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[SUB]10[/SUB] 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[SUB]10[/SUB] 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.