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
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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.
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SciScore for 10.1101/2022.05.17.22275027: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study was reviewed and approved by the institutional review boards of all participating institutions listed in Table S1.
Consent: All patients or their legally acceptable representatives provided written informed consent.Sex as a biological variable Pregnant, possibly pregnant, or breastfeeding women were also excluded. Randomization Study design: Patients with mild-to-moderate COVID-19 or asymptomatic SARS-CoV-2 infection were randomized (1:1:1) to receive ensitrelvir fumaric acid tablet 125 mg, 250 mg, or matching placebo. Blinding Randomization and blinding: Randomization of patients was performed using an interactive response technology system. Power Analysis Statistical analyses: To … SciScore for 10.1101/2022.05.17.22275027: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study was reviewed and approved by the institutional review boards of all participating institutions listed in Table S1.
Consent: All patients or their legally acceptable representatives provided written informed consent.Sex as a biological variable Pregnant, possibly pregnant, or breastfeeding women were also excluded. Randomization Study design: Patients with mild-to-moderate COVID-19 or asymptomatic SARS-CoV-2 infection were randomized (1:1:1) to receive ensitrelvir fumaric acid tablet 125 mg, 250 mg, or matching placebo. Blinding Randomization and blinding: Randomization of patients was performed using an interactive response technology system. Power Analysis Statistical analyses: To compare change from baseline in SARS-CoV-2 viral titer between each treatment group and the placebo group, 11 patients per group with COVID-19 were required to provide 82.3% power, assuming a difference of 2.5 log, a common SD of 2.2 log, and a 2-sided significance level of 10%. Table 2: Resources
Software and Algorithms Sentences Resources All analyses were performed using SAS version 9.4 (SAS Institute, Inc., Cary, NC, USA). SAS Institutesuggested: (Statistical Analysis System, RRID:SCR_008567)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:This study has some limitations. First, the small sample size and high vaccination rate limit concrete conclusions to be drawn from analyses of the clinical outcomes, such as COVID-19 symptoms including respiratory symptoms and disease exacerbation. Second, most of the enrolled patients were infected with the SARS-CoV-2 Delta variant. Our in vitro study results suggested that ensitrelvir has antiviral activity against the Omicron variant, which is the most predominant SARS-CoV-2 variant at the time of publication (12). Thus, the clinical efficacy of ensitrelvir against the Omicron variant or future variants of concern needs to be assessed in the subsequent part of this study. In addition, statistical analyses in subgroups, such as minor patients and asymptomatic patients, were not feasible owing to the limited number of patients. Further assessment of the safety and clinical efficacy of ensitrelvir in subsequent clinical studies is warranted. In conclusion, treatment with 5-day oral administration of ensitrelvir demonstrated a rapid clearance of SARS-CoV-2 and was well tolerated in patients with mild-to-moderate COVID-19 or asymptomatic SARS-CoV-2 infection. The results support further clinical development of ensitrelvir through large-scale clinical studies for the treatment of mild-to-moderate COVID-19 or asymptomatic SARS-CoV-2 infection.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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