As previously reported for Cohorts 1 and 2 of this study, R7128 has demonstrated potent short-term antiviral activity and was generally safe and well tolerated at doses of 500mg and 1500mg administered for 28 days in combination with standard of care (SOC). In Cohort 3, a new formulation of R7128 1000mg BID was administered in combination with SOC. Of the 31 patients enrolled, 25 patients received R7128 1000mg BID and six received placebo.
Approximately 88% (22 of 25) patients receiving R7128 1000mg BID with SOC for four weeks achieved undetectable hepatitis C virus (HCV) RNA levels.
This high rate of rapid virologic response (RVR) compares favorably with the 85% RVR demonstrated earlier this year with R7128 1500mg BID in combination with SOC. The preliminary safety and tolerability of R7128 1000mg BID with SOC was comparable to placebo with SOC in Cohort 3. Based on these results, R7128 1000mg BID will be among the doses carried forward into Phase IIb studies, which is expected to be submitted to the FDA this autumn.
The four-week Phase I combination clinical trial was a multiple center, observer-blinded, randomized and placebo-controlled study that was conducted in 81 treatment-naive patients chronically infected with HCV genotype 1. The primary objective was to assess the safety, tolerability, pharmacokinetics and antiviral activity of R7128 in the clinically-relevant setting of combination therapy for chronic HCV infection.
R7128, a prodrug of PSI-6130, is a nucleoside analogue polymerase inhibitor of HCV that is being developed in collaboration with Roche.
Michelle Berrey, Pharmasset’s chief medical officer, said: “This result indicates that it is unnecessary to carry the 1500 mg dose forward, since the 1000mg dose may provide a greater margin of safety over longer treatment periods without sacrificing efficacy.”