Efficacy and safety of GLS4 with entecavir vs entecavir alone in chronic hepatitis B patients: A multicenter clinical trial

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection Pub Date : 2025-03-01 DOI:10.1016/j.jinf.2025.106446

Mingyuan Zhang , Yanhang Gao , Fei Kong , Haibing Gao , Yongxiang Yi , Chao Wu , Yongning Xin , Sujun Zheng , Jiajie Lu , Tao Han , Yingren Zhao , Peng Hu , Xiaorong Mao , Qing Xie , Jie Zhang , Jinlin Hou , Zhiliang Gao , Jianqi Lian , Liang Chen , Jia Shang , Junqi Niu

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引用次数: 0

Abstract

Objectives

GLS4 is a first-in-class hepatitis B virus (HBV) capsid assembly modulator that inhibits HBV replication by interfering with assembly and disassembly of the virus nucleocapsid, this prospective, open-label, comparative, phase 2b trial evaluated the antiviral activity and safety of GLS4/ritonavir (RTV) combined with entecavir in hepatitis B e antigen-positive patients.

Methods

250 CHB patients were enrolled, including treatment-naïve patients and those interrupted anti-HBV drugs for ≥ 6 months (Part A, n=125), and patients who had taken ETV for ≥1 year and had achieved viral suppression (Part B, n=125). Patients were randomly allocated to receive 120 mg GLS4/100 mg RTV plus 0.5 mg ETV or 0.5 mg ETV monotherapy for 96 weeks.

Results

In the mid-term, in Part A (n=122), greater least-squares mean (LSM) changes from baseline were observed in the GLS4/RTV plus ETV cohort than in ETV monotherapy cohort in HBV DNA (−6.28 vs −5.72 log10 IU/ml, p=0.0005), HBsAg (−0.87 vs −0.65 log10 IU/ml, p=0.0653), HBV pgRNA (−3.83 vs −1.91 log10 copies/ml, p<0.0001); The proportions of both HBV DNA and pgRNA negative patients were 17.3% (13/75, GLS4/RTV plus ETV) and 0% (0/30, ETV monotherapy). In Part B (n=123), greater mean LSM reductions in HBsAg (−0.17 vs −0.06 log10 IU/ml, p=0.0013), HBV pgRNA (−1.61 vs −0.28 log10 copies/ml, p<0.0001) were also observed in the GLS4/RTV+ETV cohort. the proportions of both HBV DNA and pgRNA-negative patients were 71.6% (48/67, GLS4/RTV plus ETV) and 18.9% (7/37, ETV monotherapy), respectively. No patients achieved HBsAg loss at week 48.

GLS4/RTV + ETV were well tolerated, the most common adverse events were elevated alanine aminotransferase levels and hypertriglyceridemia, which were reversed by temporary GLS4/RTV discontinuation.

Conclusions

The primary analysis at week 48 showed that the antiviral efficacy of GLS4/RTV with ETV was clearly superior to that of ETV monotherapy. GLS4/RTV with ETV was well tolerated; further studies evaluating its safety and efficacy are ongoing. (clinical trial identifier: NCT04147208).

查看原文本刊更多论文

GLS4联合恩替卡韦与单独恩替卡韦治疗慢性乙型肝炎患者的疗效和安全性：一项多中心临床试验

目的：GLS4是一种首屈一指的乙型肝炎病毒（HBV）衣壳组装调节剂，通过干扰病毒核衣壳的组装和拆卸来抑制HBV复制，这项前瞻性、开放标签、比较的2b期试验评估了GLS4/利托那韦（RTV）联合恩替卡韦在乙型肝炎e抗原阳性患者中的抗病毒活性和安全性。方法：纳入250例CHB患者，包括treatment-naïve患者和抗hbv药物中断≥6个月的患者（A部分，n=125），以及服用ETV≥1年并实现病毒抑制的患者（B部分，n=125）。患者被随机分配接受120mg GLS4/100mg RTV + 0.5mg ETV或0.5mg ETV单药治疗，疗程96周。结果：中期，在A部分（n=122）中，GLS4/RTV + ETV组的HBV DNA （-6.28 vs -5.72 log10 IU/ml, p=0.0005）、HBsAg （-0.87 vs -0.65 log10 IU/ml, p=0.0653）、HBV pgRNA （-3.83 vs -1.91 log10 copies/ml, p）与基线相比的最小二乘平均值（LSM）变化大于ETV单药组。结论：第48周的初步分析显示GLS4/RTV联合ETV的抗病毒效果明显优于ETV单药组。GLS4/RTV联合ETV耐受良好；评估其安全性和有效性的进一步研究正在进行中。（临床试验编号：NCT04147208）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Infection 医学-传染病学

CiteScore

45.90

自引率

3.20%

发文量

475

审稿时长

16 days

期刊介绍： The Journal of Infection publishes original papers on all aspects of infection - clinical, microbiological and epidemiological. The Journal seeks to bring together knowledge from all specialties involved in infection research and clinical practice, and present the best work in the ever-changing field of infection. Each issue brings you Editorials that describe current or controversial topics of interest, high quality Reviews to keep you in touch with the latest developments in specific fields of interest, an Epidemiology section reporting studies in the hospital and the general community, and a lively correspondence section.