An Efficacy, Pharmacokinetics, Safety and Tolerability Study of TMC435 as Part of a Treatment Regimen for Hepatitis C-Infected Patients

• The proportion of patients with sustained virologic response (SVR) [ Time Frame: 12 weeks after the planned end of treatment (SVR12) ] [ Designated as safety issue: No ]
  To demonstrate the superiority of TMC435 versus placebo as part of a treatment regimen including peginterferon alfa-2a (PegIFNα-2a) and ribavirin.
  
  

• The number of patients with sustained virologic response (SVR) [ Time Frame: 24 weeks after the planned end of treatment (SVR24) ] [ Designated as safety issue: No ]
  To demonstrate the superiority of TMC435 versus placebo as part of a treatment regimen including peginterferon alfa-2a (PegIFNα-2a) and ribavirin.
  
  
• The number of patients with sustained virologic response (SVR) [ Time Frame: 72 weeks after the planned end of treatment (SVR72) ] [ Designated as safety issue: No ]
  To demonstrate the superiority of TMC435 versus placebo as part of a treatment regimen including peginterferon alfa-2a (PegIFNα-2a) and ribavirin.
  
  
• Antiviral activity of TMC435 [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  The antiviral activity over time of TMC435 will be compared to placebo as part of a treatment regimen including PegIFNα-2a and RBV by assessing Hepatitis C virus (HCV) ribonucleic acid (RNA) levels in plasma at different time points.
  
  
• Plasma concentrations of TMC435 [ Time Frame: Up to Week 12 ] [ Designated as safety issue: No ]
  Plasma concentrations of TMC435 will be measured to evaluate pharmacokinetic (PK) parameters of TMC435 and the relationship between TMC435 pharmacokinetics and efficacy and safety parameters.
  
  
• The number of patients in the TMC435 treatment groups who meet the response-guided treatment criteria for the shorter treatment duration [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  To determine the proportion of patients in the TMC435 treatment groups who meet the response-guided treatment criteria for the shorter treatment duration.
  
  
• The number of patients with viral breakthrough [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  The number of patients who experience viral breakthrough will be determined by measuring Hepatitis C virus (HCV) ribonucleic acid (RNA) levels in plasma.
  
  
• The number of patients with viral relapse [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  To evaluate the relapse rate after treatment in the TMC435 and placebo treatment groups.
  
  
• The number of patients who experience on-treatment failure in the TMC435 and placebo treatment groups [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  The number of patients who experience on-treatment failure will be determined by measuring Hepatitis C virus (HCV) ribonucleic acid (RNA) levels in plasma.
  
  
• Changes from baseline in the viral genome sequence of hepatitis C virus (HCV) region NS3/4A in patients not achieving a sustained virologic response (SVR) [ Time Frame: Day 1 (Baseline); Up to Week 72 ] [ Designated as safety issue: No ]
  Viral genome sequencing will be performed on ribonucleic acid (RNA) in plasma samples to monitor for the presence of drug resistant HCV variants.
  
  
• Severity score of fatigue [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  To compare the severity of fatigue as measured by the Fatigue Severity Scale (FSS) between patients treated with TMC435 versus patients on placebo as part of a treatment regimen including PegIFNα-2a and RBV.
  
  
• The number of patients reporting adverse events as a measure of safety and tolerability [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  
• The number of patients with normalized alanine transaminase (ALT) levels [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  To determine the proportion of patients with normalized ALT levels at the end of treatment and at the time points of SVR assessment.
  
  

This is a multicenter, randomized (study drug is assigned by chance), double-blind (neither sponsor, physician nor patient knows the name of the assigned study drug), Phase III study to compare the efficacy, tolerability and safety of TMC435 (in development for treatment of chronic hepatitis C virus [HCV] infection) versus placebo (a preparation containing no drug used as control) as part of a treatment regimen including peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) (both current therapies for HCV) in adult treatment-naïve patients (patients who have never taken HCV medications) with genotype 1 Hepatitis C virus (HCV) infection. The study will consist of a screening period with a maximum duration of 6 weeks, a response guided 24- or 48-week (TMC435 treatment groups) or 48-week (control group) treatment period, and a post-therapy follow-up period up to 72 weeks after the start of treatment. Patients will be randomly assigned in a 1:1:1 fashion to receive TMC435 or placebo, stratified by HCV genotype 1 subtype and IL28B genotype within each country. In the first 24 weeks, patients will receive 12 weeks TMC435 100 or 150 mg or placebo once-daily (q.d.) plus PegIFNα-2a plus RBV, after which they will continue with PegIFNα-2a and RBV. Response-guided treatment criteria will be used to determine PegIFNα-2a and RBV total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. In the control group, all patients will be required to complete 48 weeks of treatment with PegIFNα-2a and RBV. In all 3 treatment groups, there will be a post-therapy follow-up period up to 72 weeks after the start of treatment. The total study duration for each patient will be a maximum of 78 weeks (including the 6-week screening period).