Safety and antiviral activity of the HCV entry inhibitor ITX5061 in treatment-naive HCV-infected adults: A randomized, double-blind, phase 1b study

Background. Hepatitis C virus (HCV) entry involves scavenger receptor B1 (SRB1). In vitro, SRB1 inhibition by ITX5061 impedes HCV replication.Methods. Multicenter study to assess safety/activity of ITX5061 in previously untreated, noncirrhotic, HCV genotype 1 infected adults. Design included sequential cohorts of 10 subjects with ITX5061 (n = 8) or placebo (n = 2) to escalate duration (3 to 14 to 28 days) or deescalate dose (150 to 75 to 25 mg) based on predefined criteria for safety and activity (≥4 of 8 subjects with HCV RNA decline ≥1 log₁₀ IU/mL).Results. Thirty subjects enrolled in 3 cohorts: ITX5061 150 mg/day by mouth for 3 (A150), 14 (B150), and 28 (C150) days. Six subjects had grade ≥3 adverse events (one in placebo); none were treatment related. One of the 7 C150 subjects (14.3%, 95% confidence interval [CI],. 7%-55.4%) had ≥1 log₁₀ IU/mL decline in HCV RNA (1.49 log₁₀ IU/mL), whereas none of the 6 placebo, 8 A150 or 8 B150 subjects showed such decline.Conclusions. Oral ITX5061 150 mg/day for up to 28 days was safe and well tolerated. In the 28-day cohort, 1 of 7 subjects showed antiviral activity; however, predefined criteria for antiviral activity were not met at the doses and durations studied.