A Study of TMC435 in Combination With PSI-7977 (GS7977) in Chronic Hepatitis C Genotype 1-Infected Prior Null Responders To Peginterferon/Ribavirin Therapy or HCV Treatment-Naive Patients

An Exploratory Phase IIa, Randomized, Open-Label Trial to Investigate the Efficacy and Safety of 12 Weeks or 24 Weeks of TMC435 in Combination With PSI-7977 (GS7977) With Or Without Ribavirin in Chronic Hepatitis C Genotype 1-Infected Prior Null Responders To Peginterferon/Ribavirin Therapy or HCV Treatment-Naive Subjects

The purpose of this study is to investigate the efficacy and safety of TMC435 plus PSI-7977 (GS7977) with or without ribavirin in patients who are chronically infected with genotype 1 hepatitis C virus (HCV) and who did not respond to prior peginterferon/ribavirin therapy or are HCV treatment-naive (patients who never received treatment for HCV infection).

This is a Phase IIa, randomized (the study medications are assigned by chance), open label (all people know the identity of the intervention) study of TMC435 plus PSI-7977 (GS7977) with or without ribavirin. The study consists of a screening phase (6 weeks); a treatment phase (12 or 24 week period); and a posttreatment phase (follow-up period up to Week 48). Approximately 180 patients will be enrolled in this study. Patients will be sequentially enrolled into two cohorts in this study. Cohort 1 (90 patients) will include patients without advanced hepatic fibrosis who did not respond to previous PegIFN/ribavirin therapy and Cohort 2 (90 patients) will include only patients with advanced hepatic fibrosis who did not respond to previous PegIFN/ribavirin therapy or are HCV treatment-naive. Safety will be evaluated throughout the study and will include evaluations of adverse events, clinical laboratory tests, electrocardiogram, vital signs, and physical examination. The entire study duration for each participant will be approximately 48 weeks.

Inclusion Criteria:

• Chronic genotype 1 hepatitis C virus (HCV) infection
• Plasma HCV RNA of more than 10,000 IU/mL at screening
• Patients in Cohort 1 must be null responders to PegIFN/ribavirin with at least 1 documented previous course of PegIFN/ribavirin therapy for at least 12 consecutive weeks
• Patients in Cohort 2 must be null responders to PegIFN/ribavirin with at least 1 documented previous course of PegIFN/ribavirin therapy for at least 12 consecutive weeks and could also be HCV treatment-naive, meaning never received treatment with any approved or investigational drug for the treatment of HCV
• Null responders patients in Cohort 1 and Cohort 2 must meet the defined criterion for a null responder, defined as on-treatment less than 2 log10 IU/mL reduction in HCV RNA from baseline at Week 12 of the most recent PegIFN/ribavirin therapy
• Patient must have had a liver biopsy within 3 years before screening (or between screening and baseline visit) or patient must have had a liver biopsy at any time in the past which showed Metavir F3 or F4 fibrosis
• Must agree to use 2 forms of effective contraception throughout the study (male and female)

Exclusion Criteria:

• Has evidence of hepatic decompensation
• Has any liver disease of non-HCV etiology
• Has an infection/co-infection with non-genotype 1 HCV
• Has a co-infection with Human immunodeficiency virus (HIV) type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibody test at screening)
• Has a co-infection with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive)
• Has a history of malignancy within 5 years of the screening visit