tetano
Editor, Senior Moderator
EClinicalMedicine
. 2024 Apr 10:71:102582.
doi: 10.1016/j.eclinm.2024.102582. eCollection 2024 May. Efficacy and safety of GST-HG171 in adult patients with mild to moderate COVID-19: a randomised, double-blind, placebo-controlled phase 2/3 trial
Hongzhou Lu[SUP] 1 2 [/SUP], George Zhang[SUP] 3 [/SUP], John Mao[SUP] 3 [/SUP], Xiaochun Chen[SUP] 4 [/SUP], Yangqing Zhan[SUP] 5 [/SUP], Ling Lin[SUP] 6 [/SUP], Tianxiang Zhang[SUP] 3 [/SUP], Yanan Tang[SUP] 3 [/SUP], Feng Lin[SUP] 7 [/SUP], Feiyue Zhu[SUP] 8 [/SUP], Yuanlong Lin[SUP] 1 [/SUP], Yiming Zeng[SUP] 9 [/SUP], Kaiyu Zhang[SUP] 10 [/SUP], Wenfang Yuan[SUP] 11 [/SUP], Zhenyu Liang[SUP] 5 [/SUP], Ruilin Sun[SUP] 12 [/SUP], Liya Huo[SUP] 13 [/SUP], Peng Hu[SUP] 14 [/SUP], Yihua Lin[SUP] 15 [/SUP], Xibin Zhuang[SUP] 16 [/SUP], Zhaohui Wei[SUP] 17 [/SUP], Xia Chen[SUP] 17 [/SUP], Wenhao Yan[SUP] 3 [/SUP], Xiuping Yan[SUP] 3 [/SUP], Lisa Mu[SUP] 17 [/SUP], Zhuhua Lin[SUP] 17 [/SUP], Xinyu Tu[SUP] 17 [/SUP], Hongshan Tan[SUP] 3 [/SUP], Fuhu Huang[SUP] 18 [/SUP], Zhiqiang Hu[SUP] 18 [/SUP], Hongming Li[SUP] 18 [/SUP], Guoping Li[SUP] 18 [/SUP], Haijun Fu[SUP] 19 [/SUP], Zifeng Yang[SUP] 5 [/SUP], Xinwen Chen[SUP] 20 [/SUP], Fu-Sheng Wang[SUP] 21 [/SUP], Nanshan Zhong[SUP] 5 [/SUP]
Affiliations
Background: GST-HG171 is a potent, broad-spectrum, orally bioavailable small-molecule 3C like protease inhibitor that has demonstrated greater potency and efficacy compared to Nirmatrelvir in pre-clinical studies. We aimed to evaluate the efficacy 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 stratification factors including the risk level of disease progression and vaccination status. The primary efficacy endpoint was time to sustained recovery of clinical symptoms within 28 days, defined as a score of 0 for 11 COVID-19-related target symptoms for 2 consecutive days, assessed in the modified 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% confidence 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 benefits 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, confirming the potential benefits 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.
Keywords: 3CL protease; Anti SARS-CoV-2 drug; COVID-19; RCT; XBB variants.
. 2024 Apr 10:71:102582.
doi: 10.1016/j.eclinm.2024.102582. eCollection 2024 May. Efficacy and safety of GST-HG171 in adult patients with mild to moderate COVID-19: a randomised, double-blind, placebo-controlled phase 2/3 trial
Hongzhou Lu[SUP] 1 2 [/SUP], George Zhang[SUP] 3 [/SUP], John Mao[SUP] 3 [/SUP], Xiaochun Chen[SUP] 4 [/SUP], Yangqing Zhan[SUP] 5 [/SUP], Ling Lin[SUP] 6 [/SUP], Tianxiang Zhang[SUP] 3 [/SUP], Yanan Tang[SUP] 3 [/SUP], Feng Lin[SUP] 7 [/SUP], Feiyue Zhu[SUP] 8 [/SUP], Yuanlong Lin[SUP] 1 [/SUP], Yiming Zeng[SUP] 9 [/SUP], Kaiyu Zhang[SUP] 10 [/SUP], Wenfang Yuan[SUP] 11 [/SUP], Zhenyu Liang[SUP] 5 [/SUP], Ruilin Sun[SUP] 12 [/SUP], Liya Huo[SUP] 13 [/SUP], Peng Hu[SUP] 14 [/SUP], Yihua Lin[SUP] 15 [/SUP], Xibin Zhuang[SUP] 16 [/SUP], Zhaohui Wei[SUP] 17 [/SUP], Xia Chen[SUP] 17 [/SUP], Wenhao Yan[SUP] 3 [/SUP], Xiuping Yan[SUP] 3 [/SUP], Lisa Mu[SUP] 17 [/SUP], Zhuhua Lin[SUP] 17 [/SUP], Xinyu Tu[SUP] 17 [/SUP], Hongshan Tan[SUP] 3 [/SUP], Fuhu Huang[SUP] 18 [/SUP], Zhiqiang Hu[SUP] 18 [/SUP], Hongming Li[SUP] 18 [/SUP], Guoping Li[SUP] 18 [/SUP], Haijun Fu[SUP] 19 [/SUP], Zifeng Yang[SUP] 5 [/SUP], Xinwen Chen[SUP] 20 [/SUP], Fu-Sheng Wang[SUP] 21 [/SUP], Nanshan Zhong[SUP] 5 [/SUP]
Affiliations
- PMID: 38618202
- PMCID: PMC11015484
- DOI: 10.1016/j.eclinm.2024.102582
Background: GST-HG171 is a potent, broad-spectrum, orally bioavailable small-molecule 3C like protease inhibitor that has demonstrated greater potency and efficacy compared to Nirmatrelvir in pre-clinical studies. We aimed to evaluate the efficacy 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 stratification factors including the risk level of disease progression and vaccination status. The primary efficacy endpoint was time to sustained recovery of clinical symptoms within 28 days, defined as a score of 0 for 11 COVID-19-related target symptoms for 2 consecutive days, assessed in the modified 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% confidence 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 benefits 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, confirming the potential benefits 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.
Keywords: 3CL protease; Anti SARS-CoV-2 drug; COVID-19; RCT; XBB variants.