Vaniprevir with peginterferon alfa-2a and ribavirin in treatment-naive patients with chronic hepatitis C - a randomized phase 2 study

Hepatology, 04/19/2012

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.

Methods

  • 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.

Results

  • 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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