A Study of TMC435 in Combination With Pegylated Interferon Alp\Fa-2a and Ribavirin in Patients Infected With Genotype 1 Hepatitis C Virus Who Never Received Treatment (PILLAR)

Tibotec Pharmaceutical

Status and phase: Completed; Phase 2

Conditions: Hepatitis C

Treatments: Drug: Ribavirin (R); Drug: Placebo; Drug: PegIFNα-2a (P); Drug: TMC435

Study type: Interventional

Funder types: Industry

Identifiers

NCT00882908

2008-007147-13 (EudraCT Number)

CR015799

TMC435-TiDP16-C205 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy of 4 different regimens of TMC435 in combination with peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV), defined as the proportion of patients with sustained virologic response at Week 72 (patients with undetectable plasma HCV RNA [less than 25 IU per mL undetectable] at the end of treatment and at Week 72), compared to the control group receiving PegIFN and RBV in combination with TMC435-matched placebo.

Full description

This is a randomized (study medication assigned by chance), 5-arm, double-blind (neither investigator nor the participant knows the treatment that the participant receives), placebo-controlled (an inactive substance that is compared with the study medication to test whether the study medication has a real effect in clinical study) study to compare the efficacy, tolerability and safety of different TMC435 regimens combined with peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) versus PegIFNα-2a plus RBV alone in adult treatment-naive patients with chronic genotype 1 HCV infection. The study mainly consists of 3 phases: screening phase (approximately 6 weeks), treatment phase (up to 48 weeks), and follow up phase (up to 48 weeks). In the treatment phase, patients will be divided in to 5 different arms in a 1:1:1:1:1 randomized ratio. In treatment arms 1 and 2, patients will receive 12 weeks of therapy with TMC435 along with PegIFNα 2a and RBV followed by treatment with PegIFNα 2a, RBV, and TMC435-matched placebo. In treatment arms 3 and 4, patients will receive 24 weeks of therapy with TMC435, PegIFNα 2a, and RBV. In treatment arm 5 (control group), patients will receive PegIFNα 2a and RBV for 48 weeks and TMC435 matched placebo for the first 24 weeks. Collection of blood samples for efficacy evaluations will be done at scheduled visits throughout the study. Safety evaluations for adverse events, clinical laboratory tests, physical examination, vital signs and electrocardiogram will be monitored throughout the study. The total duration of the study will be up to approximately 72 weeks after initiation of treatment.

Enrollment: 386 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with documented chronic genotype-1 hepatitis C infection and with plasma HCV RNA of > 100,000 IU/mL at screening
• Patients that have not been treated before for HCV
• Patients that are of childbearing potential or have a partner of childbearing potential should agree to use 2 effective methods of contraception

Exclusion criteria

• Patients with cirrhosis or evidence of hepatic decompensation
• Co-infection with the human immunodeficiency virus (HIV)
• Any contraindication to Pegasys or Copegus therapy
• History of, or any current medical condition which could impact the safety of the patient in the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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386 participants in 5 patient groups, including a placebo group

TMC435 75 mg 12 Wks + PR 24/48

Experimental group

Description:

Participants will receive TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.

Treatment:

Drug: PegIFNα-2a (P)

Drug: TMC435

Drug: Placebo

Drug: Ribavirin (R)

TMC435 75 mg 24 Wks + PR 24/48

Experimental group

Description:

Participants will receive TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.

Treatment:

Drug: PegIFNα-2a (P)

Drug: TMC435

Drug: Placebo

Drug: Ribavirin (R)

TMC435 150 mg 12 Wks + PR 24/48

Experimental group

Description:

Participants will receive TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.

Treatment:

Drug: PegIFNα-2a (P)

Drug: TMC435

Drug: Placebo

Drug: Ribavirin (R)

TMC435 150 mg 24 Wks + PR 24/48

Experimental group

Description:

Participants will receive TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.

Treatment:

Drug: PegIFNα-2a (P)

Drug: TMC435

Drug: Placebo

Drug: Ribavirin (R)

Placebo 24 Wks + PR48

Placebo Comparator group

Description:

Participants will receive Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.

Treatment:

Drug: PegIFNα-2a (P)

Drug: Placebo

Drug: Ribavirin (R)