Ef fi cacy and safety of GST-HG171 in adult patients with mild to moderate COVID-19: a randomised, double-blind, placebo-controlled phase 2/3 trial

作者全名：Lu, Hongzhou; Zhang, George; Mao, John; Chen, Xiaochun; Zhan, Yangqing; Lin, Ling; Zhang, Tianxiang; Tang, Yanan; Lin, Feng; Zhu, Feiyue; Lin, Yuanlong; Zeng, Yiming; Zhang, Kaiyu; Yuan, Wenfang; Liang, Zhenyu; Sun, Ruilin; Huo, Liya; Hu, Peng; Lin, Yihua; Zhuang, Xibin; Wei, Zhaohui; Chen, Xia; Yan, Wenhao; Yan, Xiuping; Mu, Lisa; Lin, Zhuhua; Tu, Xinyu; Tan, Hongshan; Huang, Fuhu; Hu, Zhiqiang; Li, Hongming; Li, Guoping; Fu, Haijun; Yang, Zifeng; Chen, Xinwen; Wang, Fu-Sheng; Zhong, Nanshan

作者地址：[Lu, Hongzhou; Lin, Yuanlong] Third People Hosp Shenzhen, Shenzhen 518112, Peoples R China; [Lu, Hongzhou] Natl Clin Res Ctr Infect Dis, Shenzhen, Peoples R China; [Zhang, George; Mao, John; Zhang, Tianxiang; Tang, Yanan; Yan, Wenhao; Yan, Xiuping; Tan, Hongshan] Fujian Akeylink Biotechnol Co Ltd, Shanghai 201107, Peoples R China; [Chen, Xiaochun] Fujian Med Univ, Fuzhou, Peoples R China; [Zhan, Yangqing; Liang, Zhenyu; Yang, Zifeng; Zhong, Nanshan] Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Natl Clin Res Ctr Resp Dis, State Key Lab Resp Dis,Affiliated Hosp 1, Guangzhou, Peoples R China; [Lin, Ling] Sanya Cent Hosp, People Hosp Hainan Prov 3, Sanya, Peoples R China; [Lin, Feng] Hainan Gen Hosp, Haikou, Peoples R China; [Zhu, Feiyue] Loudi Cent Hosp, Loudi, Peoples R China; [Zeng, Yiming] Fujian Med Univ, Affiliated Hosp 2nd, Fuzhou, Peoples R China; [Zhang, Kaiyu] First Hosp Jilin Univ, Changchun, Peoples R China; [Yuan, Wenfang] Shijiazhuang Fifth Hosp, Shijiazhuang, Peoples R China; [Sun, Ruilin] Guangdong Second Prov Gen Hosp, Guangzhou, Peoples R China; [Huo, Liya] Nanyang Cent Hosp, Nanyang, Peoples R China; [Hu, Peng] Chongqing Med Univ, Affiliated Hosp 2, Chongqing, Peoples R China; [Lin, Yihua] Xiamen Univ, Affiliated Hosp 1, Xiamen, Peoples R China; [Zhuang, Xibin] Quanzhou First Hosp, Quanzhou, Fujian, Peoples R China; [Wei, Zhaohui; Chen, Xia; Mu, Lisa; Lin, Zhuhua; Tu, Xinyu] Tigermed, Hangzhou, Peoples R China; [Huang, Fuhu; Hu, Zhiqiang; Li, Hongming; Li, Guoping] Fujian Cosunter Pharmaceut Co Ltd, Fuzhou, Peoples R China; [Fu, Haijun] Shanghai Zenith Med Res Co Ltd, Shanghai, Peoples R China; [Chen, Xinwen] Guangzhou Natl Lab, Guangzhou, Guangdong, Peoples R China; [Wang, Fu-Sheng] Fifth Med Ctr Chinese PLA Gen Hosp, Natl Clin Res Ctr Infect Dis, Beijing, Peoples R China; [Zhong, Nanshan] Guangzhou Med Univ, Affiliated Hosp 1, Guangzhou 510120, Peoples R China

通信作者：Lu, HZ (通讯作者)，Third People Hosp Shenzhen, Shenzhen 518112, Peoples R China.; Zhang, GR (通讯作者)，Fujian Akeylink Biotechnol Co Ltd, Shanghai 201107, Peoples R China.; Zhong, NS (通讯作者)，Guangzhou Med Univ, Affiliated Hosp 1, Guangzhou 510120, Peoples R China.

来源：ECLINICALMEDICINE

ESI学科分类：　

WOS号：WOS:001229570700001

JCR分区：Q1

影响因子：9.6

年份：2024

卷号：71

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Anti SARS-CoV-2 drug; COVID-19; RCT; 3CL protease; XBB variants

摘要：Background GST-HG171 is a potent, broad-spectrum, orally bioavailable small -molecule 3C like protease inhibitor that has demonstrated greater potency and ef fi cacy compared to Nirmatrelvir in pre -clinical studies. We aimed to evaluate the ef fi cacy and safety of orally administered GST-HG171 plus Ritonavir in patients with coronavirus disease 2019 (COVID-19) infected with emerging XBB and non-XBB variants. Methods This randomised, double-blind, placebo -controlled phase 2/3 trial was conducted in 47 sites in China among adult patients with mild -to -moderate COVID-19 with symptoms onset <= 72 h. Eligible patients were randomised 1:1 to receive GST-HG171 (150 mg) plus Ritonavir (100 mg) or corresponding placebo tablets twice daily for 5 days, with strati fi cation factors including the risk level of disease progression and vaccination status. The primary ef fi cacy endpoint was time to sustained recovery of clinical symptoms within 28 days, de fi ned as a score of 0 for 11 COVID-19-related target symptoms for 2 consecutive days, assessed in the modi fi ed intention -to -treat (mITT) population. This trial was registered at ClinicalTrials.gov (NCT05656443) and Chinese Clinical Trial Registry (ChiCTR2200067088). Findings Between Dec 19, 2022, and May 4, 2023,1525 patients were screened. Among 1246 patients who underwent randomisation, most completed basic (21.2%) or booster (74.9%) COVID-19 immunization, and most had a low risk of disease progression at baseline. 610 of 617 who received GST-HG171 plus Ritonavir and 603 of 610 who received placebo were included in the mITT population. Patients who received GST-HG171 plus Ritonavir showed shortened median time to sustained recovery of clinical symptoms compared to the placebo group (13.0 days [95.45% con fi dence interval 12.0 - 15.0] vs. 15.0 days [14.0 - 15.0], P = 0.031). Consistent results were observed in both SARS-CoV-2 XBB (45.7%, 481/1053 of mITT population) and non-XBB variants (54.3%, 572/1053 of mITT population) subgroups. Incidence of adverse events was similar in the GST-HG171 plus Ritonavir (320/617, 51.9%) and placebo group (298/610, 48.9%). The most common adverse events in both placebo and treatment groups were hypertriglyceridaemia (10.0% vs. 14.7%). No deaths occurred. Interpretation Treatment with GST-HG171 plus Ritonavir has demonstrated bene fi ts in symptom recovery and viral clearance among low -risk vaccinated adult patients with COVID-19, without apparent safety concerns. As most patients were treated within 2 days after symptom onset in our study, con fi rming the potential bene fi ts of symptom recovery for patients with a longer duration between symptom onset and treatment initiation will require real -world studies. Funding Fujian Akeylink Biotechnology Co., Ltd. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

基金机构：Fujian Akeylink Biotechnology Co., Ltd.

基金资助正文：Fujian Akeylink Biotechnology Co., Ltd.