Vaniprevir with peginterferon alfa-2a and ribavirin in treatment-naive patients with chronic hepatitis C - a randomized phase 2 study
Hepatology, 04/19/2012Manns MP et al.
Vaniprevir is a potent HCV protease inhibitor with a predictable resistance profile and favorable safety profile that is suitable for once– or twice–daily administration.
In this double-blind, placebo-controlled, dose-ranging study, treatment-naive patients with HCV genotype 1 infection (n = 94) were randomized to receive open-label PEG-IFN alfa-2a (180 μg/week) and ribavirin (1,000-1,200 mg/day) in combination with blinded placebo or vaniprevir (300 mg bid, 600 mg bid, 600 mg qd, or 800 mg qd) for 28 days, and then open-label PEG-IFN alfa-2a and ribavirin for an additional 44 weeks.
The primary efficacy end point was rapid viral response (RVR), defined as undetectable plasma HCV RNA at week 4.
Across all doses, vaniprevir was associated with a rapid 2-phase decline in viral load, with HCV RNA levels approximately 3 log10 IU/mL lower in vaniprevir-treated patients compared with placebo recipients.
Rates of RVR were significantly higher in each of the vaniprevir dose groups compared with the control regimen (68.8%-83.3% vs 5.6%, P < 0.001 for all comparisons).
There were numerically higher, but not statistically significant, early and sustained virologic response rates with vaniprevir as compared with placebo.
Resistance profile was predictable with variants at R155 and D168 detected in a small number of patients.
No relationship between IL28B genotype and treatment outcomes was demonstrated in this study.
The incidence of adverse events was generally comparable between vaniprevir and placebo recipients; however, vomiting appeared to be more common at higher vaniprevir doses.
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