Safety, Tolerability and Antiviral Activity of GST-HG131 in Chronic Hepatitis B: A Randomized, Double-Blind Phase IIa Study

Background and aims: Chronic hepatitis B (CHB) remains a major global health burden. Current therapies rarely achieve a functional cure due to low rates of HBsAg clearance, the persistence of the viral replication template-covalently closed circular DNA (cccDNA)-and the need for lifelong treatment. GST-HG131 is a first-in-class, orally bioavailable small-molecule inhibitor of PAPD5/7, key host factors involved in HBV mRNA stabilization and HBsAg production. We evaluated the safety, tolerability and antiviral activity of GST-HG131 in patients with CHB receiving nucleos(t)ide analogue (NUC) therapy in a randomized, double-blind, placebo-controlled Phase IIa study.

Methods

This double-blind, randomized, placebo-controlled Phase IIa study evaluated the efficacy and safety of GST-HG131 in 45 CHB patients. Cohorts 1 and 2 (n = 10 each; 8 active, 2 placebo) received 30 mg or 60 mg BID for 28 days, respectively. Cohort 3 (n = 25; 20 active, five placebo) received 30 mg BID for 12 weeks. All participants were on nucleos(t)ide analog monotherapy for more than 6 months, with HBsAg between 100 and 1500 IU/mL, and serum ALT below 1× ULN.