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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen R&D Ireland
ClinicalTrials.gov Identifier:
NCT01567735
First received: January 24, 2012
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Hepatitis C
Drug: TMC435
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: 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

Resource links provided by NLM:


Further study details as provided by Janssen R&D Ireland:

Primary Outcome Measures:
  • Proportion of participants achieving sustained virologic response 12 weeks after planned end of treatment (SVR12) [ Time Frame: Up to Week 60 ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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

  • On-treatment virologic response [ Time Frame: Week 4, Week 12, Week 24, Week 36, Week 48 ] [ Designated as safety issue: No ]
    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.

  • On-treatment virologic failure [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    To evaluate on-treatment virologic failure in the overall population as well as in the different subpopulations.

  • Evaluation of the viral breakthrough rate [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    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

  • Evaluation of viral relapse rate [ Time Frame: Up to Week 48 ] [ Designated as safety issue: No ]
    To evaluate the relapse rate after TMC435 in combination with PegIFNα-2a/RBV in the overall population as well as in the different subpopulations

  • Evaluation the safety and tolerability [ Time Frame: Up to Week 72 ] [ Designated as safety issue: Yes ]
    To evaluate the safety (includes adverse events, clinical lab tests, ECG and vital signs) and tolerability of TMC435 in combination with PegIFNα-2a/RBV


Enrollment: 107
Study Start Date: March 2012
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01567735

Locations
Belgium
Antwerpen, Belgium
Brussel, Belgium
Edegem, Belgium
France
Clichy, France
Creteil N/A, France
Lyon, France
Paris, France
Villejuif Cedex, France
Sponsors and Collaborators
Janssen R&D Ireland
Investigators
Study Director: Janssen R&D Ireland Clinical Trial Janssen R&D Ireland
  More Information

No publications provided

Responsible Party: Janssen R&D Ireland
ClinicalTrials.gov Identifier: NCT01567735     History of Changes
Other Study ID Numbers: CR100695, TMC435HPC3011, 2011-004097-29
Study First Received: January 24, 2012
Last Updated: April 14, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Egypt: Ministry of Health and Population
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Janssen R&D Ireland:
Hepatitis C
TMC435HPC3011
TMC435

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

ClinicalTrials.gov processed this record on July 31, 2014