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

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 antivir...

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Published in:EClinicalMedicine 2024-01, Vol.67, p.102359-102359, Article 102359
Main Authors: Zhan, Yangqing, Lin, Zhengshi, Liang, Jingyi, Sun, Ruilin, Li, Yueping, Lin, Bingliang, Ge, Fangqi, Lin, Ling, Lu, Hongzhou, Su, Liang, Xiang, Tianxin, Pan, Hongqiu, Huang, Chaolin, Deng, Ying, Wang, Furong, Xu, Ruhong, Chen, Dexiong, Zhang, Ping, Tong, Jianlin, Wang, Xifu, Meng, Qingwei, Zheng, Zhigang, Ou, Shuqiang, Guo, Xiaoyun, Yao, Herui, Yu, Tao, Li, Weiyang, Zhang, Yu, Jiang, Mei, Fang, Zhonghao, Song, Yudi, Chen, Ruifeng, Luo, Jincan, Kang, Changyuan, Liang, Shiwei, Li, Haijun, Yanming, Huang, Haiping, Dong, Hou, Jinlin, Lei, Shao, Xiaoguang, Li, Yan, Gao, Zheng, Jingping, Zhong, Nanshan, Yang, Zifeng
Format: Article
Language:English
Subjects:
Anti SARS-CoV-2 drug
COVID-19
Drug-drug interaction
Mono-therapy
RCT
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Summary: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. 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 the intention-to-treat (ITT) population. This study is registered with ClinicalTrials.gov, NCT05620160. Between Nov 12 and Dec 30, 2022 when the zero COVID policy was abolished nationwide, a total of 1359 patients underwent randomization, 680 were assigned to leritrelvir group and 679 to placebo group. The median time to sustained clinical recovery in leritrelvir group was significantly shorter (251.02 h [IQR 188.95–428.68 h]) than that of Placebo (271.33 h [IQR 219.00–529.63 h], P = 0.0022, hazard ratio [HR] 1.20, 95% confidence interval [CI], 1.07–1.35). Further analysis of subgroups for the median time to sustained clinical recovery revealed that (1) subgroup with positive viral nucleic acid tested ≤72 h had a 33.9 h difference in leritrelvir group than that of placebo; (2) the subgroup with baseline viral load >8 log 10 Copies/mL in leritrelvir group had 51.3 h difference than that of placebo. Leritrelvir reduced viral load by 0.82 log10 on day 4 compared to placebo. No participants in either group pro
ISSN:2589-5370
2589-5370
DOI:10.1016/j.eclinm.2023.102359