A Study to Evaluate the Efficacy, Safety and Tolerability of TMC435 in Combination With PegIFN Alfa-2a (Pegasys) and Ribavirin (Copegus) in Treatment-Naïve or Treatment-Experienced, Chronic Hepatitis C Virus Genotype-4 Infected Patients (RESTORE)

July 5, 2017 updated by: Janssen R&D Ireland

An Open-Label, Single-Arm Phase III Study to Evaluate the Efficacy, Safety and Tolerability of TMC435 in Combination With PegIFN Alfa-2a (Pegasys) and Ribavirin (Copegus) in Treatment-Naïve or Treatment-Experienced, Chronic Hepatitis C Virus Genotype-4 Infected Subjects

The purpose of this study to evaluate the efficacy, safety and tolerability of TMC435 in combination with Peginterferon alfa-2a (PegINF alfa-2a) and ribavirin (RBV) in both treatment-naïve and treatment experienced, chronic hepatitis C (HCV) virus, genotype-4 infected patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is an open-label (both participant and investigator know the name of the medication given at a certain moment), single arm Phase III study, with 3 subpopulations: treatment naive, previous HCV relapser and previous HCV non-responders. The study will consist of 3 phases: a screening phase of maximum 6 Weeks, an open-label treatment phase of 24 to 48 Weeks for treatment naive patients and relapsers (response guided treatment) and 48 Weeks for non-responders, followed by a 24 Week follow-up period. The duration of participation in the study for an individual participant will be up to 54 to 78 (including screening).

Part Ia: All participants will receive 12 Weeks of triple therapy with TMC435 (150mg once daily [q.d.]), PegINF-alfa-2a (180µg per Week) and RBV (1000 to 1200 mg per day, based on weight), followed by 12 Weeks of PegINF-alfa-2a (180µg per Week) and RBV (1000 to 1200 mg per day, based on weight).

Part Ib: Participants who will need to continue treatment for another 24 Weeks (non-responders + treatment naive and relapser patients who need to continue treatment according to the response guided treatment criteria) will receive an additional 24 Weeks of PegINF-alfa 2a (180 mg per Week) and RBV (1000 to 1200 mg per day, based on weight).

Part II: 24 Week follow-up period for all participants, starting after Week 24 or Week 48.

In Part Ia, participants will have to come for 6 visits during the first month, followed by a visit once every month until Week 24 (in total 11 visits- Day1, day 3, Day 7, Day 14, day 28, Week 8, Week 12, Week 16, Week 20 and Week 24) at which safety, efficacy and tolerability will be checked.

In Part Ib, participants will have to come for 4 additional visits (Week 28, Week 36, Week 42 and Week 48) at which safety, tolerability and efficacy will be checked In the follow-up period, participants will have to come for an additional 3 visits (either Week 28, Week 36 and Week 28 or Week 52, Week 60 and Week 72) at which safety and efficacy will be checked.

Participants who withdraw prematurely will have a visit at withdrawal, 4 Weeks after withdrawal and then every 12 Weeks until 72 Weeks after baseline at which safety will be checked.

Study Type

Interventional

Enrollment (Actual)

107

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Antwerpen, Belgium
      • Brussel, Belgium
      • Edegem, Belgium
  • France
      • Clichy, France
      • Creteil, France
      • Lyon, France
      • Paris, France
      • Villejuif Cedex, France

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Genotype 4 Hepatitis C virus (HCV) infection (confirmed at screening)
  • Plasma HCV ribonucleic acid (RNA) of >10,000 IU/mL at screening
  • Participants should be either treatment-naïve or treatment-experienced (non-responder or relapser) with adequate documentation of previous response
  • Participants must have voluntarily signed an Informed Consent Form (ICF) indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. To participate in the optional pharmacogenomic component in this study (exploratory host genotyping), participants must have voluntarily signed a separate ICF for this component (where local regulations permit). Refusal to give consent for this component does not exclude a participant from participation in the core study.
  • Participants must have had a liver biopsy within 3 years prior to screening (or between screening and baseline visit) with histology consistent with chronic HCV infection

Exclusion Criteria:

  • Has an infection/co-infection with non-genotype 4 HCV
  • Has a co-infection with Human Immunodeficiency Virus (HIV) type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibodies test at screening).

  • Has any of the following laboratory abnormalities:

    1. Platelet count <90,000/mm3;
    2. Absolute neutrophil count (ANC) <1500 cells/mm3 (Blacks: <1200 cells/mm3);
    3. Hemoglobin <12 g/dL for women and <13 g/dL for men;
    4. Creatinine >1.5 mg/dL;
    5. ALT and/or AST >10 x upper limit of normal (ULN);
    6. Total serum bilirubin >1.5 x ULN;
    7. Alpha-fetoprotein [AFP] >50 ng/mL;
    8. Albumin plasma concentration <3.5 g/dL;
    9. Prothrombin time (PT) expressed as international normalized ratio (INR) >1.5. Note: retesting of abnormal laboratory values that leads to exclusion will be allowed once using an unscheduled visit during the screening period to assess eligibility.
  • Used disallowed concomitant therapy
  • Has evidence of hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TMC435
Drug: TMC435
Type=exact number, unit=mg, number=150, form=capsule, route=oral use. TMC435 capsule is taken once daily for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of participants achieving sustained virologic response 12 weeks after planned end of treatment (SVR12)
Time Frame: Up to Week 60
The primary objective is to evaluate the efficacy of TMC435 in combination with pegylated interferon alpha-2a (PegIFNα 2a)/ribavirin (RBV) with respect to the proportion of participants with chronic HCV-4 infection achieving SVR 12 weeks after planned end of treatment (SVR12) in the overall population as well as in the different subpopulations (treatment-naïve, previous relapsers and previous non-responders).
Up to Week 60

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of TMC435 with respect to proportion of participants achieving sustained virologic response 24 weeks after planned end of treatment (SVR24)
Time Frame: Up to Week 72
To evaluate the proportion of participants with SVR24, assessed 24 weeks after the planned end of treatment, in the overall population as well as in the different subpopulations
Up to Week 72
On-treatment virologic response
Time Frame: Week 4, Week 12, Week 24, Week 36, Week 48
To evaluate on-treatment virologic response at all time points with focus on Week 4, Week 12, Week 24, Week 36, Week 48, in the overall population as well as in the different subpopulations.
Week 4, Week 12, Week 24, Week 36, Week 48
On-treatment virologic failure
Time Frame: Up to Week 48
To evaluate on-treatment virologic failure in the overall population as well as in the different subpopulations.
Up to Week 48
Evaluation of the viral breakthrough rate
Time Frame: Up to Week 48
To evaluate the viral breakthrough rate on TMC435 in combination with PegIFNα-2a/RBV in the overall population as well as in the different subpopulations
Up to Week 48
Evaluation of viral relapse rate
Time Frame: Up to Week 48
To evaluate the relapse rate after TMC435 in combination with PegIFNα-2a/RBV in the overall population as well as in the different subpopulations
Up to Week 48
Evaluation the safety and tolerability
Time Frame: Up to Week 72
To evaluate the safety (includes adverse events, clinical lab tests, ECG and vital signs) and tolerability of TMC435 in combination with PegIFNα-2a/RBV
Up to Week 72

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Janssen R&D Ireland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 27, 2012

Primary Completion (Actual)

March 20, 2014

Study Completion (Actual)

March 20, 2014

Study Registration Dates

First Submitted

January 24, 2012

First Submitted That Met QC Criteria

March 28, 2012

First Posted (Estimate)

March 30, 2012

Study Record Updates

Last Update Posted (Actual)

July 7, 2017

Last Update Submitted That Met QC Criteria

July 5, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR100695
  • TMC435HPC3011 (Other Identifier: Janssen R&D Ireland)
  • 2011-004097-29 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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