A Phase 3, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of TMC435 Plus Pegylated Interferon Alfa-2a and Ribavirin Administered for 12 Weeks in Treatment-Naïve Subjects With Chronic Genotype 1 or Genotype 4 HCV Infection

Brief Summary

Detailed Description

This is a multicenter, international study where all participants will receive triple therapy with the following 3 medications: TMC435 also referred to as simeprevir (formerly known as TMC435350) which is an investigational medication in development for the treatment of chronic hepatitis C virus (HCV) infection, pegylated interferon alfa-2a (PegIFNα-2a), and ribavirin (RBV). PegIFNα-2a and RBV are commercially available therapies for HCV infection. Participants will receive treatment with TMC435, PegIFNα-2a, and RBV for 12 weeks. If blood levels of HCV ribonucleic acid (RNA) monitored at Weeks 2, 4, and 8 are below 25 IU/mL, all treatment will be stopped at Week 12. If HCV RNA values are above 25 IU/mL at Weeks 2, 4, or 8, treatment with PegIFNα-2a and RBV will continue for an additional 12 weeks (up to Week 24) unless protocol-specified stopping criteria are met at Week 4 or 12, at which time all treatment will be discontinued. The study will be conducted in 3 phases: a screening phase of maximum 6 weeks, a treatment phase extending from Day 1 (baseline) up to 12 or 24 weeks depending on the response to treatment, and a posttreatment follow-up period of 24 weeks after the participant's last planned dose of study drug. The duration of the participation (excluding screening phase) for each participant will vary between 36 and 48 weeks, depending on the response to treatment. Blood samples for laboratory analysis will be obtained from participants at protocol-specified time points during the study and participant safety will be monitored throughout the study.

Primary Outcomes

Secondary Outcomes

• The proportion (percentage) of participants who achieve rapid virologic response (RVR)(Week 4)
• The proportion (percentage) of participants with sustained virologic response 12 weeks after planned end of treatment (SVR12)(Week 24)
• The proportion (percentage) of participants with > or = 2 log decrease in hepatitis C virus (HCV) RNA at each time point(Up to Week 48)
• The proportion (percentage) of participants who achieve virologic response at Week 2 (W2VR)(Week 2)
• Change from Baseline in The Work Productivity and Activity Index (WPAI) for Hepatitis C missed work time, daily activity impairment, and productivity scores(Day 1 and at each study visit up to Week 48)
• The proportion (percentage) of participants infected wtih genotype 4 HCV with a sustained virologic response 12 weeks after planned end of treatment (SVR12)(Week 24)
• The proportion (percentage) of participants with hepatitis C virus (HCV) RNA < 25 IU/mL undetectable at each time point(Up to Week 48)
• The proportion (percentage) of participants with viral breakthrough(Up to Week 48)
• Change from Screening in liver disease stage assessment(Week -6; Week 48)
• The number of participants reporting adverse events as a measure of safety and tolerability(Up to Week 48)
• The proportion (percentage) of participants with viral relapse(Up to Week 48)
• The proportion (percentage) of participants with sustained virologic response 24 weeks after planned end of treatment (SVR24)(Week 48)
• Change from Baseline in the Hepatitis C Treatment Symptom & Impact Questionnaire (HCV SIQ) symptom and impact scores(Day 1 and at each study visit up to Week 48)
• The proportion (percentage) of participants with normalized alanine aminotransferase (ALT) levels(Up to Week 48)
• Change from Baseline in The Fatigue Severity Scale (FSS) total score(Day 1 and at each study visit up to Week 48)
• Change from Baseline in The Center for Epidemiologic Studies Depression Scale (CES-D) score(Day 1 and at each study visit up to Week 48)
• Change from Baseline in The EuroQol 5 Dimension (EQ5D) Visual Analog Scale (VAS) valuation index, and Descriptive System scores(Day 1 and at each study visit up to Week 48)