Vaniprevir plus peginterferon alfa-2a and ribavirin in treatment-experienced Japanese patients with hepatitis C virus genotype 1 infection: a randomized phase II study

Abstract

Background: Vaniprevir (MK-7009) is a hepatitis C virus (HCV) non-structural 3/4a protease inhibitor which significantly increases virologic response rates in HCV genotype (GT) 1-infected patients when added to peginterferon and ribavirin (PR).

Methods: This was a phase II, multicenter, double-blind, randomized, dose-ranging study in Japanese patients with HCV GT1 infection and previous relapse. Patients received twice daily vaniprevir 100, 300, or 600 mg, or placebo plus PR for 4 weeks then PR alone for 2 weeks. Further treatment with PR was continued up to a maximum of 72 weeks. The primary endpoint was rapid virologic response (RVR; undetectable HCV RNA at treatment week 4).

Results: Ninety patients completed 4 weeks of vaniprevir/placebo plus PR. Rates of RVR were significantly higher with vaniprevir compared with placebo (86, 95, and 76 % in the vaniprevir 100-, 300-, and 600-mg arms versus 20 % with control; p<0.001 for all comparisons). Rates of SVR, an exploratory analysis, in the vaniprevir 100-, 300-, 600-mg, and control arms were 95, 100, 100, and 72 %, respectively. No patient had virologic breakthrough or non-response while receiving vaniprevir. There were no serious adverse events (AEs) or discontinuations due to an AE during vaniprevir treatment. Diarrhea and nausea were more common with vaniprevir 600 mg than control or lower vaniprevir doses.

Conclusion: The addition of vaniprevir to PR was associated with an increase in RVR and SVR. Combined with a generally safe and well-tolerated profile, these data supported the further evaluation of vaniprevir in Japanese patients with HCV GT1 infection (#NCT00880763).

Fig. 1

Patient disposition. AE adverse event, bid twice daily, PR peginterferon alfa-2a and ribavirin

Fig. 2

Rapid virologic response. PR peginterferon alfa-2a and ribavirin, RVR rapid virologic response (undetectable HCV RNA at treatment week 4). *p < 0.001 versus PR control

Fig. 3

Mean decline in HCV RNA from baseline to week 6. bid twice daily, PR peginterferon alfa-2a and ribavirin. *Administered with peginterferon alfa-2a and ribavirin

Fig. 4

Sustained virologic response. PR peginterferon alfa-2a and ribavirin, SVR sustained virologic response (undetectable HCV RNA 24 weeks after completing last dose of treatment)

Fig. 5

Change from baseline laboratory observations during vaniprevir therapy: a alanine aminotransferase; b aspartate aminotransferase; c bilirubin; d hemoglobin. bid twice daily, PR peginterferon alfa-2a and ribavirin. *Administered with peginterferon alfa-2a and ribavirin