TMC435HPC3001 - An Efficacy, Safety and Tolerability Study for TMC435 vs Telaprevir in Combination With PegINFα-2a and Ribavirin in Chronic Hepatitis C Patients Who Were Null or Partial Responders to Prior PegINFα-2a and Ribavirin Therapy

This study is a randomized (study drug assigned by chance like flipping a coin),
double-blind (neither physician nor patient knows the name of the assigned drug),
double-dummy (patients receive both active and inactive pills also called placebo), 2-arm,
multicenter Phase III clinical study in adult treatment experienced Chronic Hepatitis C
(CHC) genotype-1 infected patients who failed to respond during at least 1 previous course
of PegINFα-2a/ RBV therapy. The purpose of the trial is to study the efficacy of TMC435 in
combination with PegINFα-2a and RBV for 48 weeks of treatment compared to the approved
regimen of telaprevir in combination with PegINFα-2a and RBV for 48 weeks of treatment. The
study will consist of a screening period (maximum 6 weeks), treatment period (48 weeks) and
post-treatment period (until 72 weeks after the start of treatment). For the first 12 weeks
one group of patients will take TMC435 and TVR placebo, plus PegINFα-2a and RBV. The other
group will take TMC435 placebo and TVR, plus PegINFα-2a and RBV. After 12 weeks, patients in
both arms will only take PegINFα-2a and RBV up to week 48. After patients stop taking study
medication, they will continue to go to the doctor's office for study visits until a total
of 72 weeks after they start study treatment. Patients will be monitored for safety
throughout the study. Study assessments at each study visit may include, but are not limited
to: blood and urine collection for testing, electrocardiogram (ECG) assessments (a
measurement of the electrical activity of your heart), patient questionnaires, and physical
examinations.

Inclusion Criteria:

- Patient must have had a liver biopsy before screening (or between the screening and
baseline visit), unless patient cannot undergo such a procedure or has evidence of
portal hypertension not associated with cirrhosis. For patients who had a liver
biopsy performed more than 2 years prior to screening or without a biopsy (because of
a contraindication or portal hypertension), a non-invasive staging assessment needs
to be available. Non-invasive staging assessments include FibroScan, MR-Elastography,
or FibroTest/FibroSure and must not be older than 6 months prior to screening

- Chronicity of hepatitis C virus (HCV) infection, as confirmed by one or both of the
following: presence of anti-HCV antibody and/or HCV ribonucleic acid (RNA) at least 6
months prior to the screening visit and/or presence of fibrosis on biopsy

- Genotype 1 HCV infection with plasma HCV RNA of >10,000 IU/mL (both confirmed at
screening)

- Patient must have had at least 1 documented previous course of treatment with
PegINFα-2a or PegINFα-2b in combination with ribavirin (RBV) (at least 12 weeks for
null responder and 20 weeks for partial responder)

Exclusion Criteria:

- Hepatic decompensation (impaired functioning of the liver), as indicated by
significant laboratory abnormalities or other active diseases

- Infection with Human Immunodeficiency Virus (HIV) or non genotype 1 hepatitis C

- Liver disease not related to hepatitis C infection

- Previous chronic hepatitis C treatment, other than PegIFN and RBV