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

• Tác giả: Liang Chen, Yunfu Chen, Haibing Gao, Yanhang Gao, Zhiliang Gao, Robert G Gish, Huanyu Gong, Tao Han, Jinlin Hou, Peng Hu, Zhenjing Jin, Fei Kong, Jianqi Lian, Shide Lin, Jiajie Lu, Lin Luo, Xiaorong Mao, Mao Mu, Junqi Niu, Huiying Rao, Jia Shang, Youwen Tan, Maorong Wang, Chao Wu, Qing Xie, Wen Xie, Yongning Xin, Dongliang Yang, Yongxiang Yi, Jie Zhang, Jiming Zhang, Mingyuan Zhang, Yingjun Zhang, Yingren Zhao, Sujun Zheng, Yulei Zhuang
• Ngôn ngữ: eng
• Ký hiệu phân loại: 973.928 Administration of George Bush, 1989-1993
• Thông tin xuất bản: England : The Journal of infection , 2025
• Bộ sưu tập: NCBI
• ID: 643876

Tóm tắt

 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 120mg GLS4/100mg RTV plus 0.5mg ETV or 0.5mg 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).