Institute of Liver Studies, Kings College Hospital, London, United Kingdom.
Yonsei University College of Medicine, Brain Korea 21 Project of Medical Science, Seoul, Republic of Korea.
Toronto Liver Centre, Toronto, Ontario, Canada.
Gilead Sciences, Inc, Foster City, CA.
Center for the Study and Research on Hepatitis, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Chung-Ang University Hospital, Seoul, South Korea.
Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Stanford University Medical Center, Palo Alto, California.
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.
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.
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.