Clinical trial NCT00996476: A Study to Assess the Effectiveness, Safety, and Pharmacokinetics of TMC435 in Combination With Peginterferon Alfa-2a and Ribavirin in Hepatitis-C Infected Patients
Official title: A Phase II, Randomized, Open-label Study in Japan to Investigate the Efficacy, Safety and Pharmacokinetics of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Treatment naïve, Genotype 1, Chronic Hepatitis C Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C, Chronic
Keywords: Hepatitis C
Hepatitis C virus
Interferon Alfa-2a
Ribavirin
Viral RNA
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2009-10-16
Enrollment: 92
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 effectiveness, safety and pharmacokinetics (Explores what the body does to the medication) of TMC435350 in combination with Peginterferon Alfa-2a and Ribavirin in genotype 1 hepatitis C virus infected Japanese participants who have never received treatment for their hepatitis C infection.

Detailed description: This is a Phase 2, randomized (The study medication is assigned by chance.), 5-arm, open label (All people know the identity of the intervention.), multicentre (study conducted at multiple sites) study. Approximately, 84 participants will be randomized to 5 different arms in a 2:2:1:1:1 ratio. In treatment arms 1 and 2, participants will receive 12 weeks of triple therapy (use of 3 medications) with TMC435 50 or 100 mg once daily plus Peginterferon Alfa-2a and Ribavirin followed by 12 weeks of treatment with Peginterferon Alfa-2a and Ribavirin. In treatment arms 3 and 4, participants will receive 24 weeks of triple therapy with TMC435 50 or 100 mg once daily plus Peginterferon Alfa-2a and Ribavirin. In treatment arm 5 (control group), participants will receive Peginterferon Alfa-2a and Ribavirin for 48 weeks. This study will consist a screening phase of upto 6 weeks, treatment phase of upto 48 weeks and a post treatment follow-up period of 24 weeks. Safety evaluations will include assessment of adverse events, clinical laboratory tests, vital signs, and cardiovascular safety.

Eligibility criteria: Inclusion Criteria:

* Participants with documented chronic hepatitis C infection as evidenced by presence of HCV antibody at least 6 months (180 days) prior to the informed consent. - Participants with genotype 1 HCV infection. - Participants with plasma HCV RNA level of ≥ 5.0 log10 IU/mL at screening.

Exclusion Criteria:

* Participants diagnosed with hepatic cirrhosis or hepatic failure. - Participants with any other liver disease than hepatitis C. - Participants with infection/co-infection with non-genotype 1 HCV.

Primary outcomes:
measure: Change in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels From Baseline to Week 4
timeFrame: Day 1 (Baseline) and Week 4
measure: The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels During the Study
timeFrame: Weeks 4, 12, 24 or 48, and EOT (up to Week 24 or 48)
measure: The Percentage of Participants With a Decrease of Greater Than or Equal to 2 log10 IU/mL From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Through the Post-treatment Follow-up Period
timeFrame: Days 1 (4 hr), 1 (8 hr), 3, Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, 24,28, 36, 42, 48, 52, 60, 72, and EOT (up to Week 24 or 48)
measure: The Percentage of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Undetectable or Below the Limit of Quantification (<1.2 log10 IU/mL Detectable) During Treatment and During Post Treatment Follow-up
timeFrame: Week 4, 12, 24, 36, 48, EOT (up to Week 24 or 48), and Week 60 and 72
measure: The Number of Participants With Viral Breakthrough
timeFrame: Up to EOT (up to Week 24 or 48)
measure: The Percentage of Participants With Viral Relapse
timeFrame: Week 36 or 60
measure: Actual Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values up to Week 24 in the Post-treatment Follow-up Period
timeFrame: Baseline, Week 4, 12, 24, 48, EOT (up to Week 24 or 48), and Weeks 60 and 72
measure: The Number of Participants With Alanine Aminotransaminase (ALT) Values Within the Normal Range at the End-of-treatment (EOT)
timeFrame: Day 1, Weeks 24, 48, and EOT (up to Weeks 24 or 48)
measure: The Percentage of Participants With Sustained Virologic Response (SVR)
timeFrame: SVR4 (up to Week 28 or Week 52), SVR12 (up to Weeks 36 or 60), and SVR24 (up to Weeks 48 or 72)
measure: Predose Plasma Concentrations (C0h) of TMC435 (Sparse Blood Sampling)
timeFrame: Weeks 4, 12, and 24
measure: Predose Plasma Concentrations (C0h) of TMC435 (Intensive Blood Sampling)
timeFrame: Weeks 4 to 6
measure: The Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24) for TMC435
timeFrame: within 15 minutes and at 1, 2, 4, 6, 8, 12, and 24 hours post-dose between Week 4 and Week 6 after the initiation of treatment
measure: Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435
timeFrame: within 15 minutes and at 1, 2, 4, 6, 8, 12, and 24 hours post-dose between Week 4 and Week 6 after the initiation of treatment
measure: The Number of Participants Who Met Virologic Stopping/Continuation Rules and Completed All Study Medications
timeFrame: Week 24
Secondary outcomes:
Other outcomes:
Locations:
city: Amagasaki
country: Japan
city: Hiroshima N/A
country: Japan
city: Kagoshima
country: Japan
city: Kawasaki
country: Japan
city: Kitakyushu
country: Japan
city: Kurume
country: Japan
city: Kyoto
country: Japan
city: Matsumoto
country: Japan
city: Musashino
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: Suita
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:
citation: Hayashi N, Seto C, Kato M, Komada Y, Goto S. Once-daily simeprevir (TMC435) with peginterferon/ribavirin for treatment-naive hepatitis C genotype 1-infected patients in Japan: the DRAGON study. J Gastroenterol. 2014 Jan;49(1):138-47. doi: 10.1007/s00535-013-0875-1. Epub 2013 Sep 5.