A Study of TMC435 in Genotype 1, Hepatitis C-infected Patients Who Relapsed After Previous Interferon (IFN)-Based Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier:
NCT01290731
First received: February 3, 2011
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

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 relapsed after previous interferon (IFN)-based therapy in Japan.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: TMC435
Drug: Pegylated interferon (pegIFN alpha-2a)
Drug: Ribavirin (RBV)
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III, Open-label Trial in Japan to Investigate the Efficacy and Safety of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Genotype 1, Hepatitis C-infected Subjects Who Relapsed After Previous IFN-based Therapy

Resource links provided by NLM:


Further study details as provided by Janssen Pharmaceutical K.K.:

Primary Outcome Measures:
  • The Percentage of Participants With a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12) [ Time Frame: Week 36 or 60 ] [ Designated as safety issue: No ]
    The table below shows the percentage of participants with an SVR12 defined as participants with undetectable plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at the end of treatment (Week 24 or 48) who also had undetectable plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) 12 weeks after the last dose of treatment (Week 36 or 60).


Secondary Outcome Measures:
  • The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24) [ Time Frame: Week 48 or 60 ] [ Designated as safety issue: No ]
    The table below shows the percentage of participants with a SVR24 defined as participants with undetectable plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at the end of treatment (Week 24 or 48) and at 24 weeks after the last dose of treatment (Week 48 or 72).

  • 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 [ Time Frame: Days 3 and 7, Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 36, 48, 60, 72, EOT, and follow-up (FU) Weeks 4, 12, and 24 ] [ Designated as safety issue: No ]
    The table below shows the percentage of participants with greater than or equal to 2 log10 IU/mL drop from baseline in plasma HCV RNA at each time point during treatment, at the end of treatment (Week 24 or 48), and post-treatment follow-up.

  • The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT) [ Time Frame: Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT ] [ Designated as safety issue: No ]
    The table below shows the percentage of participants with undetectable HCV RNA (defined as less than 1.2 log10 IU/mL during treatment at Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT [Week 24 or 48]).

  • The Number of Participants With Viral Breakthrough [ Time Frame: Day 1 until end of treatment (EOT [Week 24 or 48]) ] [ Designated as safety issue: No ]
    Viral breakthrough was defined as a confirmed increase of greater than 1 log10 IU/mL in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels from the lowest level reached or a confirmed value of plasma HCV RNA of > 2.0 log10 IU/mL in particpants whose plasma HCV RNA level had previously been below 1.2 log10 IU/mL detectable or undetectable during the treatment period. The table below shows that no viral breakthrough was noted in any participants during the treatment period of the study.

  • The Number of Participants Demonstrating Viral Relapse [ Time Frame: Up to 72 weeks ] [ Designated as safety issue: No ]
    The table below shows the number of participants who demonstrated viral relapse, defined as undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) at end of treatment (EOT) and detectable HCV RNA during follow-up or detectable HCV RNA at the time points of sustained virologic response (SVR) assessment . The incidence of viral relapse was calculated for participants with undetectable HCV RNA levels at EOT and with at least one follow-up HCV RNA measurement.

  • Plasma Concentrations of TMC435 [ Time Frame: Overall (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12) ] [ Designated as safety issue: No ]
    The table below shows median (range) TMC435 predose plasma concentration (C0h) values and the TMC435 maximum plasma concentration (Cmax) values for all participants who received TMC435 for up to 12 weeks. "Overall" is the median exposure estimate using all available data for each participant in the study.Sparse blood samples were collected during the study (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12).

  • Area Under the Plasma Concentration-time Curve From 0 to 24 Hrs (AUC24h) for TMC435 [ Time Frame: Overall (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12) ] [ Designated as safety issue: No ]
    The table below shows the median (range) AUC24h values for TMC435 for all participants who received TMC435 for up to 12 weeks. "Overall" is the median exposure estimate using all available data for each participant in the study. Sparse blood samples were collected during the study (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12).

  • The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT) [ Time Frame: EOT (Week 24 or 48) ] [ Designated as safety issue: No ]
    The table below shows the number of participants with abnormal ALT levels at baseline (Day 1) who achieved normalization of ALT levels (defined as an ALT value less than or equal to the Upper Limit of Normality [ie, 40 IU/mL] at EOT). At baseline, 15/49 participants had abnormal ALT levels.


Enrollment: 49
Study Start Date: January 2011
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TMC435 100 mg 12 Wks + PR24/48
Participants will receive TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24 (PR 24). Treatment will be stopped at Week 24 in participants who achieve plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (<) 1.2 log10 IU/mL detectable or undetectable of at Week 4, and undetectable HCV RNA levels at Week 12. All other participants will continue PR until Week 48 (PR 48).
Drug: TMC435
100-mg capsule once daily for 12 weeks
Drug: Pegylated interferon (pegIFN alpha-2a)
180 mcg injected subcutaneously (by a syringe under the skin) once weekly for 12 to 36 weeks (or until Week 48).
Other Name: PEGASYS
Drug: Ribavirin (RBV)
200-mg tablets (daily dose: 600-1000 mg) taken orally (by mouth) two times a day for 12 to 36 weeks (or until Week 48).
Other Name: COPEGUS

Detailed Description:

This is a single-arm study to evaluate the efficacy and safety of TMC435 in combination with the standard of care (SoC), PegIFNα-2a (P) and ribavirin (R), in adult, genotype 1 HCV-infected participants who relapsed after previous IFN-based therapy in Japan. The study objective is to evaluate the efficacy of TMC435 by the percentage of participants with undetectable HCV ribonucleic acid (RNA). Participants will receive 12 weeks of treatment with TMC435 (100 mg) once daily plus PR followed by 12 or 36 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 µg 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), taken orally two times a day after meals. The participants will receive oral capsules of TMC435 (100 mg) once daily up to Week 12.

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must have chronic genotype 1 HCV with HCV RNA level >= 5.0 log10 IU/mL
  • Participant relapsed after 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 pegIFN or ribavirin therapy
  • History of, or any current medical condition, which could impact the safety of the patient in the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01290731

Locations
Japan
Hiroshima, Japan
Ichikawa, Japan
Kagoshima, Japan
Matsumoto, Japan
Musashino, Japan
Ohmura, Japan
Osaka, Japan
Sapporo, Japan
Suita, Japan
Touon, Japan
Sponsors and Collaborators
Janssen Pharmaceutical K.K.
Investigators
Study Director: Janssen Pharmaceutical K.K. Clinical Trial Janssen Pharmaceutical K.K.
  More Information

No publications provided

Responsible Party: Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier: NCT01290731     History of Changes
Other Study ID Numbers: CR017698, TMC435HPC3008
Study First Received: February 3, 2011
Results First Received: October 17, 2013
Last Updated: December 16, 2013
Health Authority: Japan: Japan Pharmaceuticals And Medical Devices Evaluation Center
Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Janssen Pharmaceutical K.K.:
Hepatitis C, Chronic
Hepatitis C virus
Interferon Alfa-2a
Ribavirin
Viral RNA

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Interferons
Ribavirin
Peginterferon alfa-2a
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014