Safety, pharmacokinetics, and antiviral efficacy of the novel capsid assembly modulator GST-HG141 in patients with chronic hepatitis B: a phase 1 trial with a randomized, placebo-controlled design.
Min Wu, Jiajia Mai, Hong Zhang, George Zhang, John Mao, Yanan Tang, Wenhao Yan, Wenqiang Wu, Jinlin Hou, Xieer Liang, Zhihong Liu, Yanhua Ding, Junqi Niu
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引用次数: 0
Abstract
In preclinical studies, GST-HG141, a novel hepatitis B virus (HBV) capsid assembly modulator displayed potent anti-HBV activity in vitro and strong efficacy in HBV animal models. A randomized, double-blind, ascending phase 1b trial assessed the pharmacokinetics, safety, and efficacy of GST-HG141 in chronic hepatitis B (CHB) individuals. Thirty treatment-naïve CHB patients were enrolled in three cohorts (25, 50, and 100 mg twice orally after meals daily) over 28 days, with 10 subjects per cohort (8:2 ratio for GST-HG141 and placebo). Dose-related safety and tolerability, pharmacokinetic profiles, and drug responses were evaluated. GST-HG141 exhibited a generally favorable safety profile across all doses with predominantly mild adverse reactions, including three cases of grade 1 transaminase elevations. Significant reductions in HBV DNA and pregenomic RNA (pgRNA) levels were observed across all doses of (25, 50, and 100 mg of GST-HG141, twice-daily) after 28 days of treatment. Pharmacokinetic analysis showed a consistent linear trend in GST-HG141 concentrations, with mean trough concentrations ranging from 75 to 240 ng/mL. These concentrations adequately covered the protein binding-adjusted EC50 (16.89 ng/mL) by factors of 4.4, 11.1, and 14.6 for doses of 25, 50, and 100 mg, respectively. Our study demonstrated GST-HG141's well-tolerated profile up to 100 mg over 4 weeks, alongside robust antiviral activity in CHB patients, supporting its progression into further clinical investigation for CHB management.
期刊介绍:
Virology Journal is an open access, peer reviewed journal that considers articles on all aspects of virology, including research on the viruses of animals, plants and microbes. The journal welcomes basic research as well as pre-clinical and clinical studies of novel diagnostic tools, vaccines and anti-viral therapies.
The Editorial policy of Virology Journal is to publish all research which is assessed by peer reviewers to be a coherent and sound addition to the scientific literature, and puts less emphasis on interest levels or perceived impact.