Clinical trial NCT01292239: A Phase III Study of TMC435 in Treatment-naive, Genotype 1, Hepatitis C-infected Patients
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C, Chronic
Keywords: Hepatitis C, Chronic
Hepatitis C
Hepatitis C virus
Interferon Alfa-2a
Ribavirin
Viral RNA
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2011-02-09
Enrollment: 183
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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

Primary outcomes:
measure: 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)
timeFrame: EOT (up to Week 24 or 48) and 12 weeks after the EOT (up to Week 36 or 60)
Secondary outcomes:
measure: 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)
timeFrame: EOT (up to Week 24 or 48) and 24 weeks after the after the last dose of treatment (up to Week 48 or 72)
measure: 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
timeFrame: Day 3, Day 7 and Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60, 72, EOT (up to Week 24 or 48), FU Week 4, 12, and 24
measure: 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)
timeFrame: Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
measure: The Number of Participants With Viral Breakthrough
timeFrame: Up to EOT (up to Week 24 or 48)
measure: The Number of Participants Demonstrating Viral Relapse
timeFrame: Up to Week 72
measure: The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT)
timeFrame: Baseline (Day 1) to EOT (up to Week 24 or 48)
measure: 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
timeFrame: Week 24
measure: Plasma Concentrations of TMC435
timeFrame: Overall (ie, Up to Week 12)
measure: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
timeFrame: Overall (Up to Week 12)
Other outcomes:
Locations:
city: Amagasaki
country: Japan
city: Chiba
country: Japan
city: Chuo
country: Japan
city: Hiroshima
country: Japan
city: Ichikawa
country: Japan
city: Ikeda
country: Japan
city: Inashiki
country: Japan
city: Iruma
country: Japan
city: Kagoshima
country: Japan
city: Kanazawa
country: Japan
city: Kitakyushu
country: Japan
city: Kumamoto
country: Japan
city: Kurume
country: Japan
city: Kyoto
country: Japan
city: Matsumoto
country: Japan
city: Musashino
country: Japan
city: Nagoya
country: Japan
city: Niigata
country: Japan
city: Nishinomiya
country: Japan
city: Ohmura
country: Japan
city: Osaka-Sayama
country: Japan
city: Osaka
country: Japan
city: Sakai
country: Japan
city: Sapporo
country: Japan
city: Sendai
country: Japan
city: Tokyo
country: Japan
city: Touon
country: Japan
city: Yokohama
country: Japan
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K. Clinical Trial
role: STUDY_DIRECTOR
References: