Clinical trial NCT01288209: A Phase III Study of TMC435 in Genotype 1, Hepatitis C-infected Participants Who Failed to Respond to Previous IFN-based Therapy
Official title: A Phase III, Randomized, Open-label, Two-arm Trial in Japan to Investigate the Efficacy and Safety of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Hepatitis C, Genotype 1-Infected Subjects Who Failed to Respond to Previous IFN-based Therapy
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: 2011-02-02
Enrollment: 106
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 in combination with peginterferon alfa-2a (PegIFNα-2a) and ribavirin in genotype 1 hepatitis C virus (HCV)-infected participants who failed to respond to previous interferon (IFN)-based therapy in Japan.

Detailed description: This is a randomized (study drug assigned by chance), 2-arm, open-label study to evaluate the efficacy and safety of TMC435 (also referred to as jnj-38733214-aaa) in combination with the standard of care (SoC) therapy consisting of peginterferon alfa-2a (PegIFNα-2a ) and ribavirin (RBV) administered according to the manufacturer's prescribing information in adult, genotype 1 hepatitis C virus (HCV)-infected participants who failed to respond to previous interferon (IFN)-based therapy in Japan. The study objective is to evaluate the efficacy of TMC435 by the proportion of participants with undetectable HCV ribonucleic acid (RNA). Participants will receive 12 weeks of treatment with TMC435 (100 mg) once daily plus PegIFNα-2a (P) and RBV P) followed by 12 or 36 weeks of treatment with PR OR participants will receive 24 weeks of treatment with TMC435 (100 mg) once daily plus PR followed by 24 weeks of treatment with PR. TMC435 is a 100-mg capsule and will be taken orally (via the mouth). Treatment with PR will last 24 or 48 weeks: Pegylated interferon is supplied as a vial containing 1.0 mL solution with 180 mcg PegIFNα-2a and will be 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. Participants will receive oral capsules of TMC435 (100 mg) once daily up to Week 12 or 24.

Eligibility criteria: Inclusion Criteria:

* Participant must have chronic genotype 1 HCV infection with HCV RNA level \>= 5.0 log10 IU/mL
* Participant failed to respond to previous IFN-based therapy
* Participant 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 PegIFNα-2a 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 (Week 24 or 48) and Week 36 or 60
Secondary outcomes:
measure: The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the End of Treatment (EOT) and 24 Weeks After the Last Dose of Treatment (SVR24)
timeFrame: EOT (Week 24 or 48) and 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, 48, 60, 72, EOT, and Follow-up (FU) Weeks 4, 12, and 24
measure: The Percentage of Participants With Undetectable Plasma 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
measure: The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels During Treatment for Participants Who Did Not Achieve Undetectable Plasma HCV RNA Levels at Week 12
timeFrame: Weeks 24, 48, EOT (Weeks 24 or 48), SVR12 (Weeks 36 or 60), and SVR24 (Weeks 48 or 72)
measure: The Number of Participants With Viral Breakthrough During the Study
timeFrame: Up to EOT (Week 24 or 48)
measure: The Number of Participants Demonstrating Viral Relapse During the Study
timeFrame: Up to 72 weeks
measure: The Number Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT)
timeFrame: EOT (Week 24 or 48)
measure: The Percentage of Participants Who Met Response Guided Treatment (RGT) Criteria and Completed Treatment With Peginterferon Alpha-2a (PegIFNα-2a) and Ribavirin (RBV) at Week 24
timeFrame: Week 24
measure: Plasma Concentrations of TMC435
timeFrame: Week 12, Week 24, and Overall (Weeks 4, 12, and 24)
measure: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
timeFrame: Week 12, Week 24, and Overall (Weeks 4, 12, and 24)
Other outcomes:
Locations:
city: Amagasaki
country: Japan
city: Ichikawa
country: Japan
city: Kagoshima
country: Japan
city: Kanazawa
country: Japan
city: Kawasaki
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: Nishinomiya
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: Yokohama
country: Japan
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K. Clinical Trial
role: STUDY_DIRECTOR
References: