Rapid Decline of Viral RNA in Hepatitis C Patients Treated With VX-950: A Phase Ib, Placebo-Controlled, Randomized Study

Background & Aims: VX-950 specifically inhibits the NS3·4A protease of hepatitis C and has antiviral activity in vitro. This phase I, placebo-controlled, double-blind study evaluated the antiviral activity, pharmacokinetics, and safety of VX-950 in patients with chronic hepatitis C (CHC). Methods: Thirty-four patients with genotype 1 CHC were randomized to receive placebo or VX-950 at doses of 450 mg or 750 mg every 8 hours or 1250 mg every 12 hours for 14 days. Of the 34 participants, 27 (79%) had failed prior treatment. Patients were monitored for safety and tolerability of VX-950. Plasma VX-950 concentrations and HCV RNA levels were measured. Results: VX-950 was well tolerated and had substantial antiviral effects: viral loads dropped ≥2 log 10 in all 28 patients treated with VX-950 and ≥3 log 10 in 26 (93%) of the 28 patients. In the 750-mg-dose group, which had the highest trough plasma drug concentrations, the median reduction of HCV RNA was 4.4 log 10 after 14 days. In the 450-mg and 1250-mg groups, the maximal effect was seen between days 3 and 7 of dosing, and median HCV RNA increased between days 7 and 14; median reductions at day 14 were 2.4 log 10 and 2.2 log 10 , respectively. Median alanine aminotransferase levels decreased during dosing in all VX-950 groups. Conclusions: VX-950 was well tolerated and demonstrated substantial antiviral activity. Some patients had viral breakthrough during dosing, related to selection of variants with decreased sensitivity to VX-950. The results support further studies of VX-950 in patients with CHC.