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)

Janssen (J&J Innovative Medicine)

Status and phase

Completed

Phase 3

Conditions

Hepatitis C

Treatments

Drug: TMC435

Study type

Interventional

Funder types

Industry

Identifiers

NCT01567735

TMC435HPC3011 (Other Identifier)

2011-004097-29 (EudraCT Number)

CR100695

Details and patient eligibility

About

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.

Full 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.

Enrollment

107 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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)