Author information
1
Institute of Liver Studies, Kings College Hospital, London, United Kingdom.
2
Yonsei University College of Medicine, Brain Korea 21 Project of Medical Science, Seoul, Republic of Korea.
3
Toronto Liver Centre, Toronto, Ontario, Canada.
4
Gilead Sciences, Inc, Foster City, CA.
5
Center for the Study and Research on Hepatitis, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
6
Chung-Ang University Hospital, Seoul, South Korea.
7
Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
8
Stanford University Medical Center, Palo Alto, California.
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, multicenter, double-blind, randomized, placebo-controlled study.
METHODS:
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 12 weeks; tenofovir disoproxil fumarate (300-mg daily) was administered daily for 48 weeks. 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.
RESULTS:
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. 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-α induction that correlated with grade of influenza-like adverse events. Overall, vesatolimod is safe and well-tolerated in CHB patients. Though consistent dose-dependent pharmacodynamic induction of ISGs was demonstrated, it did not result in clinically significant HBsAg decline.