Safety and efficacy of GST-HG141, a novel HBV capsid assembly modulator, for the treatment of chronic hepatitis B patients with low-level viremia: a randomized, double-blind, placebo-controlled, multicenter phase II study

作者：Chong Wang, Fei Kong, Haibing Gao, Dachuan Cai, Guoqiang Zhang, Guoqiang Zhang, Qin Ning, Bei Zhong, Zhijun Su, Zhijun Su, Guicheng Wu, Jinlin Hou, John Mao, Tianxiang Zhang, Wenqiang Wu, Xiu‐Ping Yan, Xiu‐Ping Yan, Guoping Li, Yanhang Gao, George Zhang, George Zhang, Junqi Niu · 发表于：EClinicalMedicine · 年份：2025 · DOI：10.1016/j.eclinm.2025.103400 · 被引用次数：7 · 研究领域：Hepatitis B Virus Studies、Hepatitis C virus research、RNA Interference and Gene Delivery

Background Chronic hepatitis B (CHB) remains a major global health challenge with no curative therapies. Approximately 15–40% of patients treated with current standard-of-care antiviral therapies such as nucleos(t)ide analogs (NUCs), including entecavir (ETV) and tenofovir (TDF/TAF), fail to fully suppress serum HBV DNA, resulting in persistent low-level viremia (LLV), which is associated with increased risks of cirrhosis, liver failure, and hepatocellular carcinoma. GST-HG141, a novel HBV capsid assembly modulator, previously demonstrated favorable safety and antiviral activity in a Phase Ib study, offering a promising approach for LLV management in CHB patients. Methods This Phase II, randomized, double-blind, placebo-controlled, multicenter trial evaluated the efficacy and safety of GST-HG141 in CHB patients with LLV. It is registered at ClinicalTrials.gov (NCT05637541) and Clinical Trial Registry (GST-HG141-II-02). From January 2023 to July 2024, 144 patients were screened across ten research centers in China, and 90 eligible participants were enrolled. All participants had been on NUC therapy for over one year, with serum HBV DNA levels between 20 and 2000 IU/mL and ALT ≤5 × ULN. Patients were randomized 1:1:1 to receive low-dose GST-HG141 (50 mg BID, n = 30), high-dose GST-HG141 (100 mg BID, n = 30), or placebo ( n = 30), administered orally for 24 weeks. The primary endpoint was the proportion of participants achieving serum HBV DNA levels below the lower limit of dete...