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
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
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.
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.
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)