{"title":"Efficacy and Safety of Ensitrelvir for Asymptomatic or Mild COVID-19: An Exploratory Analysis of a Multicenter, Randomized, Phase 2b/3 Clinical Trial","authors":"Norio Ohmagari, Hiroshi Yotsuyanagi, Yohei Doi, Masaya Yamato, Takumi Imamura, Hiroki Sakaguchi, Hideki Yamanaka, Ryosuke Imaoka, Akimasa Fukushi, Genki Ichihashi, Takao Sanaki, Yuko Tsuge, Takeki Uehara, Hiroshi Mukae","doi":"10.1111/irv.13338","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>This phase 2b/3, randomized, placebo-controlled trial explored the efficacy and evaluated the safety of ensitrelvir. This trial involved individuals with asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with mild symptoms of coronavirus disease 2019 (COVID-19).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>The trial was conducted at 57 medical institutions in Japan, South Korea, and Vietnam (study period: January 6–August 14, 2022). Eligible participants were randomized (1:1:1) to the ensitrelvir 125-mg, ensitrelvir 250-mg, or placebo group, received the allocated intervention orally, and were followed up until Day 28. Participants self-rated the severity of 14 typical COVID-19 symptoms and recorded the data in an electronic diary.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>In total, 572 participants (194, 189, and 189 in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively) were included in the intention-to-treat population. Ensitrelvir 125-mg group observed a 77% reduction in the risk of developing any of the 14 COVID-19 symptoms or fever and a 29% reduction in the risk of worsening of such symptoms or fever versus placebo (statistically nonsignificant). The viral RNA, viral titer, and time to infectious viral clearance observed a statistically significant decrease versus placebo. Most treatment-related adverse events (TEAEs) were mild to moderate in severity, and the most common TEAE observed across groups was a decrease in high-density lipoprotein.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Our exploratory results suggest a potential reduction in the risk of development or worsening of COVID-19 symptoms with ensitrelvir. Ensitrelvir showed antiviral efficacy and was well tolerated.</p>\n </section>\n \n <section>\n \n <p><b>Trial Registration:</b> Japan Registry of Clinical Trials identifier: jRCT2031210350.</p>\n </section>\n </div>","PeriodicalId":13544,"journal":{"name":"Influenza and Other Respiratory Viruses","volume":"18 6","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/irv.13338","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Influenza and Other Respiratory Viruses","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/irv.13338","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
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Abstract
Background
This phase 2b/3, randomized, placebo-controlled trial explored the efficacy and evaluated the safety of ensitrelvir. This trial involved individuals with asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with mild symptoms of coronavirus disease 2019 (COVID-19).
Methods
The trial was conducted at 57 medical institutions in Japan, South Korea, and Vietnam (study period: January 6–August 14, 2022). Eligible participants were randomized (1:1:1) to the ensitrelvir 125-mg, ensitrelvir 250-mg, or placebo group, received the allocated intervention orally, and were followed up until Day 28. Participants self-rated the severity of 14 typical COVID-19 symptoms and recorded the data in an electronic diary.
Results
In total, 572 participants (194, 189, and 189 in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively) were included in the intention-to-treat population. Ensitrelvir 125-mg group observed a 77% reduction in the risk of developing any of the 14 COVID-19 symptoms or fever and a 29% reduction in the risk of worsening of such symptoms or fever versus placebo (statistically nonsignificant). The viral RNA, viral titer, and time to infectious viral clearance observed a statistically significant decrease versus placebo. Most treatment-related adverse events (TEAEs) were mild to moderate in severity, and the most common TEAE observed across groups was a decrease in high-density lipoprotein.
Conclusions
Our exploratory results suggest a potential reduction in the risk of development or worsening of COVID-19 symptoms with ensitrelvir. Ensitrelvir showed antiviral efficacy and was well tolerated.
Trial Registration: Japan Registry of Clinical Trials identifier: jRCT2031210350.
期刊介绍:
Influenza and Other Respiratory Viruses is the official journal of the International Society of Influenza and Other Respiratory Virus Diseases - an independent scientific professional society - dedicated to promoting the prevention, detection, treatment, and control of influenza and other respiratory virus diseases.
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