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
| Autor: | Hiroshi Mukae, Hiroshi Yotsuyanagi, Norio Ohmagari, Yohei Doi, Takumi Imamura, Takuhiro Sonoyama, Takahiro Fukuhara, Genki Ichihashi, Takao Sanaki, Keiko Baba, Yosuke Takeda, Yuko Tsuge, Takeki Uehara |
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| Rok vydání: | 2022 |
| Předmět: |
Adult
Pharmacology SARS-CoV-2 ensitrelvir SARSCoV- 2 3C-like protease inhibitor COVID-19 S-217622 Antiviral Agents COVID-19 Drug Treatment proof-of-concept study Infectious Diseases Japan Double-Blind Method Anti-Infective Agents viral titer Japanese Humans RNA Viral Protease Inhibitors Pharmacology (medical) Enzyme Inhibitors |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 66 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.00697-22 |
| Popis: | 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 ARSCoV- 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 (log10 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 log10 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). Antimicrobial Agents and Chemotherapy, 66(10), art. no. e0069722; 2022 |
| Databáze: | OpenAIRE |
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