Clinical trial NCT01366638: A Study of TMC435 in Participants With Genotype 1 Hepatitis C Virus (HCV) Infection
Official title: A Phase III, Open-Label Study in Japan to Assess the Efficacy and Safety of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2b and Ribavirin in Hepatitis C, Genotype 1 Infected Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C, Chronic
Keywords: Hepatitis C, Chronic
TMC435
Hepatitis C
Hepatitis C virus
Interferon Alfa-2b
Ribavirin
Viral ribonucleic acid
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2011-06-06
Enrollment: 79
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of TMC435 in combination with peginterferon alfa-2b and ribavirin in chronic genotype 1 hepatitis C virus (HCV)-infected participants who are treatment-naive or treatment-experienced (prior relapser or non-responder to Interferon-based therapy) in Japan.

Detailed description: This is an open-label study (all people involved know the identity of the intervention) to evaluate the efficacy and safety of TMC435 (also referred to as jnj-38733214-aaa) in combination with the standard of care therapy (SoC: peginterferon \[pegIFN\] alfa-2b and ribavirin) in adult, genotype 1 hepatitis C virus (HCV)-infected participants who are treatment-naive (never received treatment for HCV), prior relapsers (relapsed after previous interferon \[IFN\]-based therapy), or non-responders (failed to respond to previous IFN-based therapy) in Japan. The study objective is to evaluate the efficacy, safety, and pharmacokinetics of TMC435. A sufficient number of participants who are treatment-naive, prior relapsers to treatment with IFN-based therapy, and prior non-responders to treatment with IFN-based therapy will be enrolled and assigned to 1 of 3 panels (referred to as treatment groups). Participants who are treatment-naive or prior relapsers to IFN-based therapy will receive 12 weeks of treatment with TMC435 (100 mg) once daily with pegIFN alfa-2b and ribavirin (PR) followed by an additional 12 or 24 weeks of treatment with PR. Participants who are non-responders to IFN-based therapy will receive 12 weeks of treatment with TMC435 (100 mg) once daily with PR followed by an additional 36 weeks of treatment with PR. TMC435 is a 100-mg capsule and will be taken orally by mouth. The SoC treatment will consist of Pegylated interferon (PegIFN alpha-2b) (1.5 mcg/kg) injected with a syringe subcutaneously (under the skin) once weekly and ribavirin 200-mg capsules (daily dose: 600-1000 mg based on body weight) taken orally by mouth 2 times a day after meals for 24 or 48 weeks.

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 (treatment-naive), relapsed after previous IFN-based therapy (prior relapser) or failed to respond to previous IFN-based therapy (non-responder)
* 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 peg-IFN 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 12 Weeks After the Actual End of Treatment (SVR12)
timeFrame: Week 36 or 60
measure: The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24)
timeFrame: 24 weeks after the last dose of treatment (Week 48 or 72)
measure: The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During Treatment and at the End of Treatment
timeFrame: Weeks 4, 12, 24, 36, 48, 60, 72, and EOT (up to Week 48)
measure: The Number of Participants With Viral Breakthrough
timeFrame: Up to 48 Weeks
measure: The Number of Participants Demonstrating Viral Relapse
timeFrame: Up to 72 weeks
measure: The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal Limit of ALT at the End of Treatment (EOT)
timeFrame: Up to Week 48
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, 48, 60, 72, EOT (up to Week 24 or 48), follow-up (FU) Week 4, 12, and 24
measure: The Percentage of Participants Who Met Response Guided Treatment (RGT) Criteria and Completed Treatment With Peginterferon Alpha-2b (PegIFNα-2b) and Ribavirin (RBV) at Week 24
timeFrame: Week 24 or 48
measure: The Area Under the Plasma Concentration-Time Curve (From 0 to 24 Hours) (AUC24h)
timeFrame: Overall (Up to Week 12)
measure: Plasma Concentrations of TMC435
timeFrame: Overall (Up to Week 12)
Secondary outcomes:
Other outcomes:
Locations:
city: Amagasaki
country: Japan
city: Ikeda
country: Japan
city: Kawasaki
country: Japan
city: Kumamoto
country: Japan
city: Niigata
country: Japan
city: Ohmura
country: Japan
city: Osaka
country: Japan
city: Sakai
country: Japan
city: Sapporo
country: Japan
city: Suita
country: Japan
city: Tokyo
country: Japan
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K. Clinical Trial
role: STUDY_DIRECTOR
References: