A Safety and Effectiveness Study of TMC435 in Chronic, Genotype 1, Hepatitis C Patients Who Failed to Previous Standard Treatment

A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Efficacy, Tolerability, Safety and Pharmacokinetics of TMC435 as Part of a Treatment Regimen Including PegIFNa-2a and Ribavirin in HCV Genotype 1 Infected Subjects Who Failed Previous Standard Therapy

The purpose of this study is to determine the efficacy, safety and tolerability of different regimens of TMC435 with standard treatment compared to standard treatment alone in participants with chronic, genotype 1, hepatitis C virus (HCV) infection who has failed previous treatment with pegylated interferon (Peg-INF-alfa-2a) and ribavirin (RBV).

The study is a randomized (study drug assigned by chance), double-blind (neither physician nor participant knows the name of the assigned drug), placebo-controlled Phase IIb trial with TMC435 in participants with chronic, genotype 1, hepatitis C virus (HCV) infection who have failed standard treatment with pegylated interferon (Peg-INF-alfa-2a) and ribavirin (RBV). The study will compare the efficacy, tolerability and safety of different regimens with TMC435 combined with standard treatment (Peg-INF-alfa-2a and RBV) versus standard treatment alone. The trial will consist of a screening period of maximum 6 weeks, a 48-week treatment period, and a 24-week follow-up period. Participants will be eligible to enroll in the trial if they failed to respond to a prior course of standard treatment or relapsed following standard treatment. Participants will be randomly assigned to receive TMC435 with standard treatment for 12 weeks followed by standard treatment (plus placebo) for 36 weeks, TMC435 (100 mg or 150 mg once a day) with standard treatment for 24 weeks followed by standard treatment (plus placebo) for 24 weeks, TMC435 (100 mg or 150 mg once a day) with standard treatment for 48 weeks, or a placebo with standard treatment for 48 weeks.

Inclusion Criteria:

• Must have chronic hepatitis C infection as evidenced by liver biopsy, anti-hepatitis C virus (HCV) and HCV RNA positive
• Must have chronic hepatitis C infection (genotype 1) with HCV RNA level greater than10000 IU/mL
• Patient must have failed at least 1 prior course of peg interferon (Peg-IFN-alfa-2a)/ribavirin (RBV) therapy (standard treatment)
• Must be willing to use 2 effective methods of birth control for up to 7 months after last dose of study medication

Exclusion Criteria:

• Has an evidence of decompensated liver disease
• Co-infection with any other Hepatitis C virus genotype or co-infection with the human immunodeficiency virus (HIV)
• Has a medical condition which is a contraindication to Peg-INF or RBV therapy
• Have had history of, or any current medical condition which could impact the safety of the patient in the study