Academic Journal
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
| Title: | 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 |
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| Authors: | 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 |
| Source: | Virology Journal, Vol 21, Iss 1, Pp 1-9 (2024) |
| Publisher Information: | BMC, 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Infectious and parasitic diseases |
| Subject Terms: | Antiviral therapy, Hepatitis B, Pharmacokinetics, Tolerability, Capsid assembly modulator, Infectious and parasitic diseases, RC109-216 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1743-422X 24714399 |
| Relation: | https://doaj.org/toc/1743-422X |
| DOI: | 10.1186/s12985-024-02584-8 |
| Access URL: | https://doaj.org/article/5bc7956a24714399bc46609ddbf4cb5e |
| Accession Number: | edsdoj.5bc7956a24714399bc46609ddbf4cb5e |
| Database: | Directory of Open Access Journals |
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| ISSN: | 1743422X 24714399 |
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| DOI: | 10.1186/s12985-024-02584-8 |
| Published in: | Virology Journal |
| Language: | English |