Leritrelvir for the treatment of mild or moderate COVID-19 without co-administered ritonavir: a multicentre randomised, double-blind, placebo-controlled phase 3 trial

作者：Yangqing Zhan, Zhengshi Lin, Jingyi Liang, Ruilin Sun, Yueping Li, Bingliang Lin, Fangqi Ge, Ling Lin, Hongzhou Lu, Liang Su, Tianxin Xiang, Hongqiu Pan, Chaolin Huang, Ying Deng, Furong Wang, Ruhong Xu, Dexiong Chen, Ping Zhang, Jianlin Tong, Xifu Wang, Qingwei Meng, Zhigang Zheng, Shaoxiang Ou, Xiaoyun Guo, Herui Yao, Changyuan Yu, Weiyang Li, Yu Zhang, Mei Jiang, Zhonghao Fang, Yudi Song, Ruifeng Chen, Jincan Luo, Changyuan Kang, Shiwei Liang, Haijun Li, Huang Yanming, Dong Haiping, Jinlin Hou, Shao Lei, Li Xiaoguang, Gao Yan, Jingping Zheng, Nanshan Zhong, Zifeng Yang · 发表于：EClinicalMedicine · 年份：2023 · DOI：10.1016/j.eclinm.2023.102359 · 被引用次数：48 · 研究领域：SARS-CoV-2 and COVID-19 Research、COVID-19 Clinical Research Studies、Diverse Scientific Research Studies

Background Leritrelvir is a novel α-ketoamide based peptidomimetic inhibitor of SARS-CoV-2 main protease. A preclinical study has demonstrated leritrelvir poses similar antiviral activities towards different SARS-CoV-2 variants compared with nirmatrelvir. A phase 2 clinical trial has shown a comparable antiviral efficacy and safety between leritrelvir with and without ritonavir co-administration. This trial aims to test efficacy and safety of leritrelvir monotherapy in adults with mild-to-moderate COVID-19. Methods This was a randomised, double-blind, placebo-controlled, multicentre phase 3 trial at 29 clinical sites in China. Enrolled patients were from 18 to 75 years old, diagnosed with mild or moderate COVID-19 and not requiring hospitalization. Patients had a positive SARS-CoV-2 nucleic acid test (NAT) and at least one of the COVID-19 symptoms within 48 h before randomization, and the interval between the first positive SARS-CoV-2 NAT and randomization was ≤120 h (5 days). Patients were randomly assigned in a 1:1 ratio to receive a 5-day course of either oral leritrelvir 400 mg TID or placebo. The primary efficacy endpoint was the time from the first dose to sustained clinical recovery of all 11 symptoms (stuffy or runny nose, sore throat, shortness of breath or dyspnea, cough, muscle or body aches, headache, chills, fever ≥37 °C, nausea, vomiting, and diarrhea). The safety endpoint was the incidence of adverse events (AE). Primary and safety analyses were performed in th...