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

Condition(s) targeted: Hepatitis C, Chronic

Intervention: Placebo (Drug); TMC435 (Drug); Peginterferon alfa-2a (pegIFN alfa-2a) (Drug); Ribavirin (RBV) (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Janssen Pharmaceutical K.K.

Official(s) and/or principal investigator(s):
Janssen Pharmaceutical K.K. Clinical Trial, Study Director, Affiliation: Janssen Pharmaceutical K.K.

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.

Official title: A Phase III, Randomized, Double-blind, Placebo-controlled Trial in Japan to Investigate the Efficacy and Safety of TMC435 vs. Placebo as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Treatment-Naive, Genotype 1, Hepatitis C-infected Subjects

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: The Percentage of Participants With a Sustained Virologic Response at the End of Treatment (EOT) and 12 Weeks After the Last Dose of Treatment (SVR12)

Secondary outcome:

The Percentage of Participants With a Sustained Virologic Response at the End of Treatment (EOT) and 24 Weeks After the Last Dose of Treatment (SVR24)

The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up

The Percentage of Participants With Undetectable Plasma Levels of Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)

The Number of Participants With Viral Breakthrough

The Number of Participants Demonstrating Viral Relapse

The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT)

The Percentage of Participants in the TMC435 Treatment Group Who Met Response Guided Treatment (RGT) Criteria and Completed Treatment With Peginterferon Alpha-2a (PegIFN Alpha-2a) and Ribavirin (RBV) at Week 24

Plasma Concentrations of TMC435

Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435

Detailed description: 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.

Minimum age: 20 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

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

Amagasaki, Japan

Chiba, Japan

Chuo, Japan

Hiroshima, Japan

Ichikawa, Japan

Ikeda, Japan

Inashiki, Japan

Iruma, Japan

Kagoshima, Japan

Kanazawa, Japan

Kitakyushu, Japan

Kumamoto, Japan

Kurume, Japan

Kyoto, Japan

Matsumoto, Japan

Musashino, Japan

Nagoya, Japan

Niigata, Japan

Nishinomiya, Japan

Ohmura, Japan

Osaka-Sayama, Japan

Osaka, Japan

Sakai, Japan

Sapporo, Japan

Sendai, Japan

Tokyo, Japan

Touon, Japan

Yokohama, Japan

Starting date: February 2011
Last updated: December 16, 2013