Safety and Efficacy of Vesatolimod (GS-9620) in Patients with Chronic Hepatitis B (CHB) Who Are Not Currently on Antiviral Treatment
- Authors
- Agarwal, Kosh; Ahn, Sang Hoon; Elkhashab, Magdy; Kim, Kyungpil; Lau, Audrey H.; Gaggar, Anuj; Subramanian, Mani; McHutchison, John G.; Andreone, Pietro; Kim, Hyung J.; Chuang, Wan-Long; Nguyen, Mindie H.
- Issue Date
- Nov-2018
- Publisher
- WILEY
- Keywords
- HBeAg; HBsAg; hepatitis B virus; immune response; TLR7; vesatolimod
- Citation
- HEPATOLOGY, v.66, no.11, pp 497A - 498A
- Journal Title
- HEPATOLOGY
- Volume
- 66
- Number
- 11
- Start Page
- 497A
- End Page
- 498A
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/56442
- DOI
- 10.1111/jvh.12942
- ISSN
- 0270-9139
1527-3350
- Abstract
- Vesatolimod is an oral agonist of toll-like receptor 7 designed to minimize systemic exposure and side effects. We assessed the safety and efficacy of vesatolimod in viremic chronic hepatitis B (CHB) patients not currently on oral antiviral treatment (OAV) in a phase 2, multicentre, double-blind, randomized, placebo-controlled study. A total of 192 patients stratified by HBeAg status and alanine aminotransferase level were randomized 2:2:2:1 to receive oral vesatolimod (1-, 2- or 4-mg) or placebo once weekly for 12weeks; tenofovir disoproxil fumarate (300-mg daily) was administered daily for 48weeks. Efficacy was assessed by quantitative serum HBsAg decline at Week 24 from baseline. In addition to safety assessments, changes in whole-blood interferon-stimulated gene (ISG) transcripts and serum cytokines were explored. Most patients were male (64.1%) and HBeAg-negative (60.9%) at baseline. Among vesatolimod-treated patients, most (60.4%-69.1%) experienced 1 treatment-emergent adverse event; the majority were mild or moderate in severity. No clinically meaningful differences in HBsAg changes from baseline were observed between treatment groups. No patients experienced HBsAg loss, while 3 patients experienced HBeAg loss and hepatitis B e-antibody seroconversion at week 48. HBV DNA suppression rates were similar across all treatment arms at Week 24. ISG15 induction was dose-dependent and did not correlate with HBsAg changes. A small proportion of patients exhibited dose-dependent interferon- induction that correlated with grade of influenza-like adverse events. Overall, vesatolimod is safe and well tolerated in CHB patients. Although consistent dose-dependent pharmacodynamic induction of ISGs was demonstrated, it did not result in clinically significant HBsAg decline.
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