A Phase III Study of TMC435 in Treatment-naive, Genotype 1, Hepatitis C-infected Patients

• Proportion of patients with sustained virological response (SVR12) [ Time Frame: Follow-up Week 12 ] [ Designated as safety issue: No ]
• Proportion of patients with 2 log 10 IU/mL or more decrease in HCV RNA [ Time Frame: Up to 72 weeks ] [ Designated as safety issue: No ]
• Proportion of patients with undetectable HCV RNA [ Time Frame: Up to 72 weeks ] [ Designated as safety issue: No ]
• Proportion of patients with viral breakthrough [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
• Proportion of patients showing viral relapse [ Time Frame: Up to 72 weeks ] [ Designated as safety issue: No ]
• Number of patients with adverse events [ Time Frame: Up to 72 weeks ] [ Designated as safety issue: Yes ]
• Plasma concentrations of TMC435 [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]

The purpose of this study is to evaluate the efficacy and safety of TMC435 compared with placebo in combination with peginterferon alfa-2a (pegIFN alfa-2a) and ribavirin in treatment-naive patients with chronic genotype 1 hepatitis C virus (HCV) infection in Japan.

This is a randomized (study drug assigned by chance), 2-arm, double-blind study to evaluate the efficacy and safety of TMC435 (also referred to as jnj-38733214-aaa) versus placebo in combination with the standard of care (SoC) therapy (peginterferon alfa-2a [pegIFN alfa-2a] and ribavirin) in adult treatment-naïve patients (who never received treatment for HCV) with chronic genotype 1 HCV infection in Japan. The study objective is to evaluate and compare the efficacy of TMC435 vs placebo by the proportion of the patients with undetectable HCV ribonucleic acid (RNA). In the TMC435 treatment group, patients will receive 12 weeks of treatment with TMC435 (100 mg) once daily plus SoC followed by an additional 12 or 36 weeks of treatment with SoC. In the placebo treatment group, patients will receive 12 weeks of treatment with placebo once daily plus SoC followed by an additional 36 weeks of treatment with SoC. TMC435 is a 100-mg capsule and will be taken orally by mouth. The SoC treatment will be given for 24 or 48 weeks. Pegylated interferon is supplied as a vial containing 1.0 mL solution with 180 mcg pegIFN alpha-2a and administered subcutaneously (injected by a syringe under the skin) once weekly. Ribavirin is given as 200-mg tablets (daily dose: 600-1000 mg based on body weight), and taken orally by mouth two times a day after meals.

• Drug: Placebo
  Placebo capsule taken by mouth once daily for 12 weeks
• Drug: TMC435
  100-mg capsule taken by mouth once daily for 12 weeks
• Drug: Peginterferon alfa-2a (pegIFN alfa-2a)
  PegIFN alfa-2a (PEGASYS) will be administered according to the manufacturer's prescribing information as 180 mcg once weekly injected subcutaneous (under the skin) for up to 24-48 weeks for patients randomized to TMC435 and for up to 48 weeks for patients randomized to placebo.
  Other Name: PEGASYS
• Drug: Ribavirin (RBV)
  RBV (COPEGUS) will be administered according to the manufacturer's prescribing information. If body weight is > 80 kg the total daily dose of RBV will be 1000 mg, taken by mouth as 400 mg (2 tablets of 200 mg) after breakfast and 600 mg (3 tablets of 200 mg) after supper. If body weight is > 60 kg to <=80 kg the total daily dose will be 800 mg, taken by mouth as 400 mg (2 tablets of 200 mg per intake) after breakfast and supper. If body weight is <=60 kg the total daily dose of RBV will be 600 mg, taken by mouth as 200 mg (1 tablet of 200 mg) after breakfast and 400 mg (2 tablets of 200 mg) after supper. Total duration of RBV will be 24-48 weeks.
  Other Name: COPEGUS

• Experimental: TMC435
  TMC435 100-mg capsule taken orally (by mouth) once daily for 12 weeks along with Standard of Care (SoC) treatment (ie, peginterferon alfa-2a [pegIFN alfa-2a] subcutaneous (under the skin) injections once weekly and ribavirin (RBV) tablets twice daily for up to 24 or 48 weeks).
  Interventions:

  • Drug: TMC435
  • Drug: Peginterferon alfa-2a (pegIFN alfa-2a)
  • Drug: Ribavirin (RBV)
• Experimental: Placebo
  Placebo capsule identical in appearance to TMC435 taken orally once daily for 12 weeks along with Standard of Care (SoC) treatment (ie, peginterferon alfa-2a [pegIFN alfa-2a] subcutaneous (under the skin) injections once weekly and ribavirin (RBV) tablets twice daily for up to 48 weeks).
  Interventions:

  • Drug: Placebo
  • Drug: Peginterferon alfa-2a (pegIFN alfa-2a)
  • Drug: Ribavirin (RBV)

Inclusion Criteria:

• Patient must have chronic genotype 1 HCV infection with HCV RNA level >= 5.0 log10 IU/mL
• Patient has never received treatment for HCV
• Patient must be willing to use contraceptive measures from the time of informed consent to 6 months after last dose of study medication

Exclusion Criteria:

• Co-infection with any other HCV genotype or co-infection with the human immunodeficiency virus (HIV)
• Diagnosed with hepatic cirrhosis or hepatic failure
• A medical condition which is a contraindication to pegIFN or ribavirin therapy
• History of, or any current medical condition which could impact the safety of the patient in the study