Placebo-controlled trial of antibody to connective tissue growth factor (CTGF) in HBV liver fibrosis

Abstract

INTRODUCTION: CTGF is a matricellular glycoprotein and central mediator of tissue remodeling and fibrosis. CTGF levels are elevated in viral hepatitis and NASH liver tissue. Inhibition of CTGF-expression prevents liver fibrosis in mouse models. FG-3019 is a human mAb to CTGF that is being developed to treat advanced liver fibrosis. METHODS: 114 subjects with chronic hepatitisB (HBV) in Asia, naı¨ve to antiviral therapy with Ishak C2 (amended to C3), were randomized 2:1 to entecavir+FG-3019 (15 and 45 mg/kg IV, Q3 W, for 45 weeks) or entecavir+placebo. The primary endpoint was the proportion of subjects with C1 point improvement in Ishak fibrosis score at 48 weeks (response rate) versus baseline. ClinicalTrials.gov: NCT01217632. RESULTS: Although the study is closed, data are not yet unblinded. FG-3019/placebo with entecavir showed excellent safety and tolerability at both dose levels: Neither local nor systemic allergic reactions were reported. At end of treatment,[95 % of subjects had undetectable viral load, and the majority normalized ALTs. No abnormal laboratory trends and no evidence of liver decompensation were noted. Ishak score change is available in 76 subjects: 21 had decrease of 1 point, 18 of 2 points, 5 of C3 points, 26 were stable and 6 had increased score for an aggregate response rate of 57.9 %. Unblinded data will be presented at a subsequent congress. CONCLUSIONS: FG-3019+ entecavir was well-tolerated in subjects with advanced HBV fibrosis and FG-3019 did not appear to impair entecavir’s antiviral efficacy.