Efficacy and Safety of Ensitrelvir for Asymptomatic or Mild COVID-19: An Exploratory Analysis of a Multicenter, Randomized, Phase 2b/3 Clinical Trial

IF 4.3 4区医学 Q1 INFECTIOUS DISEASES

Influenza and Other Respiratory Viruses Pub Date : 2024-06-18 DOI:10.1111/irv.13338

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

{"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":null,"pages":null},"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}

引用次数: 0

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.

Abstract Image

查看原文本刊更多论文

Ensitrelvir 治疗无症状或轻度 COVID-19 的有效性和安全性：一项多中心、随机、2b/3 期临床试验的探索性分析。

研究背景这项2b/3期随机安慰剂对照试验探讨了ensitrelvir的疗效并评估了其安全性。该试验涉及无症状感染严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2）的患者和有轻微症状的2019年冠状病毒病（COVID-19）患者：试验在日本、韩国和越南的57家医疗机构进行（研究时间：2022年1月6日至8月14日）。符合条件的参与者被随机（1:1:1）分配到安斯瑞韦 125 毫克组、安斯瑞韦 250 毫克组或安慰剂组，口服所分配的干预药物，并随访至第 28 天。参与者对 14 种典型 COVID-19 症状的严重程度进行自我评分，并将数据记录在电子日记中：共有 572 名参与者（恩西替雷韦 125 毫克组、恩西替雷韦 250 毫克组和安慰剂组分别有 194 人、189 人和 189 人）被纳入意向治疗人群。与安慰剂相比，恩西特雷韦 125 毫克组出现 14 种 COVID-19 症状中任何一种症状或发热的风险降低了 77%，此类症状或发热恶化的风险降低了 29%（无统计学意义）。与安慰剂相比，病毒 RNA、病毒滴度和感染性病毒清除时间均出现统计学意义上的显著下降。大多数治疗相关不良事件（TEAEs）的严重程度为轻度至中度，各组中最常见的TEAE是高密度脂蛋白下降：我们的探索性研究结果表明，使用恩西雷韦可能会降低COVID-19症状发生或恶化的风险。恩西特韦具有抗病毒疗效，且耐受性良好：日本临床试验登记处标识符：jRCT2031210350。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Influenza and Other Respiratory Viruses 医学-病毒学

CiteScore

7.20

自引率

4.50%

发文量

120

审稿时长

6-12 weeks

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. Influenza and Other Respiratory Viruses is an Open Access journal. Copyright on any research article published by Influenza and Other Respiratory Viruses is retained by the author(s). Authors grant Wiley a license to publish the article and identify itself as the original publisher. Authors also grant any third party the right to use the article freely as long as its integrity is maintained and its original authors, citation details and publisher are identified.