■GST-HG171是一种有效的,广谱,口服生物可利用的小分子3C样蛋白酶抑制剂在临床前研究中显示出比Nirmatrelvir更高的效力和功效。我们旨在评估口服GST-HG171加利托那韦治疗感染新出现的XBB和非XBB变体的2019年冠状病毒病(COVID-19)患者的疗效和安全性。
■这是随机的,双盲,安慰剂对照2/3期试验在中国的47个地点对症状发作≤72小时的轻中度COVID-19成年患者进行。符合条件的患者以1:1随机分配接受GST-HG171(150mg)加利托那韦(100mg)或相应的安慰剂片,每天两次,持续5天,分层因素包括疾病进展的风险水平和疫苗接种状态。主要疗效终点是28天内临床症状持续恢复的时间,定义为连续2天11项COVID-19相关目标症状的评分为0,在改良意向治疗(mITT)人群中进行评估。该试验在ClinicalTrials.gov(NCT05656443)和中国临床试验注册中心(ChiCTR2200067088)注册。
■在2022年12月19日至2023年5月4日之间,对1525名患者进行了筛查。在1246名接受随机化的患者中,完成最基本(21.2%)或加强(74.9%)COVID-19免疫,大多数患者在基线时疾病进展风险较低.接受GST-HG171加利托那韦的617人中的610人和接受安慰剂的610人中的603人被包括在mITT人群中。与安慰剂组相比,接受GST-HG171加利托那韦的患者临床症状持续恢复的中位时间缩短(13.0天[95.45%置信区间12.0-15.0]vs.15.0天[14.0-15.0],P=0.031)。在SARS-CoV-2XBB中观察到一致的结果(45.7%,mITT群体的481/1053)和非XBB变体(54.3%,572/1053的mITT群体)亚组。GST-HG171加利托那韦(320/617,51.9%)和安慰剂组(298/610,48.9%)的不良事件发生率相似。安慰剂组和治疗组最常见的不良事件是高甘油三酯血症(10.0%vs.14.7%)。没有死亡发生。
■GST-HG171加利托那韦治疗在低风险接种COVID-19的成年患者的症状恢复和病毒清除方面显示出益处,没有明显的安全问题。在我们的研究中,由于大多数患者在症状发作后2天内接受治疗,对于症状发作和开始治疗之间持续时间较长的患者,确认症状恢复的潜在益处将需要真实世界的研究。
■福建阿基联生物技术有限公司Ltd.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Fujian Akeylink Biotechnology Co., Ltd.