TMC435-TiDP16-C205: A Phase II Study of TMC435 in Combination With Pegylated Interferon Alpha-2a and Ribavirin in Patients Infected With Genotype 1 Hepatitis C Virus Who Never Received Treatment (PILLAR)

This study has been completed.
Sponsor:
Information provided by:
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00882908
First received: April 16, 2009
Last updated: June 28, 2012
Last verified: June 2012
  Purpose

The purpose of this study is to test the efficacy, safety and tolerability of 4 different regimens of TMC435 given in combination with Peginterferon alfa-2a and ribaviron (Standard of Care) as compared to placebo + Standard of Care.


Condition Intervention Phase
Hepatitis C
Drug: Ribavirin PegIFNalpha-2a
Drug: TMC435 Ribavirin
Drug: PegIFNalpha-2a
Drug: TMC435 TMC435 Placebo
Drug: TMC435 Placebo Ribavirin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase IIb, Randomized, Double-blind, Placebo-controlled Trial to Investigate the Efficacy, Tolerability, Safety and Pharmacokinetics of TMC435 as Part of a Treatment Regimen Including Peginterferonalfa-2a and Ribavirin in Treatment-naive Genotype 1hepatitis C-infected Subjects.

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • The primary objective of the trial is to evaluate the efficacy of 4 different regimens of TMC435 in combination with SoC, defined as the proportion of patients with undetectable HCV RNA (< 10 IU/mL) 24 weeks after the planned end of treatment. [ Time Frame: 24 weeks after the planned end of treatment. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate TMC435 antiviral activity [ Time Frame: every study visit ] [ Designated as safety issue: No ]
  • Evaluate TMC435 safety [ Time Frame: every study visit ] [ Designated as safety issue: No ]
  • Evaluate TMC435 tolerability [ Time Frame: every study visit ] [ Designated as safety issue: No ]

Enrollment: 386
Study Start Date: May 2009
Study Completion Date: April 2011
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001

Ribavirin

PegIFNalpha-2a 1000-1200mg tab twice a day for 24wks Weekly 180µg injection for 24wks,TMC435 TMC435 Placebo 75mg tab/day for 12wks Placebo tab/day for 12wks

Drug: Ribavirin PegIFNalpha-2a
1000-1200mg tab twice a day for 24wks Weekly 180µg injection for 24wks
Drug: TMC435 TMC435 Placebo
75mg tab/day for 12wks Placebo tab/day for 12wks
Experimental: 002

Ribavirin

PegIFNalpha-2a 1000-1200mg tab twice a day for 24wks Weekly 180µg injection for 24wks,TMC435 TMC435 Placebo 150mg tab/day for 12 wks Placebo tab/day for 12 wks

Drug: Ribavirin PegIFNalpha-2a
1000-1200mg tab twice a day for 24wks Weekly 180µg injection for 24wks
Drug: TMC435 TMC435 Placebo
150mg tab/day for 12 wks Placebo tab/day for 12 wks
Experimental: 003
PegIFNalpha-2a Weekly 180µg injection for 24wks,TMC435 Ribavirin 75mg tab/day for 24 wks 1000-1200mg tab twice a day for 24wks
Drug: TMC435 Ribavirin
75mg tab/day for 24 wks 1000-1200mg tab twice a day for 24wks
Drug: PegIFNalpha-2a
Weekly 180µg injection for 24wks
Experimental: 004
PegIFNalpha-2a Weekly 180µg injection for 24wks,TMC435 Ribavirin 150mg tab/day for 24 wks 1000-1200mg tab twice a day for 24wks
Drug: TMC435 Ribavirin
150mg tab/day for 24 wks 1000-1200mg tab twice a day for 24wks
Drug: PegIFNalpha-2a
Weekly 180µg injection for 24wks
Active Comparator: 005
PegIFNalpha-2a Weekly 180µg injection for 48wks,TMC435 Placebo Ribavirin Placebo tab/day for 24 wks 1000-1200mg tab twice/day for 48 wks
Drug: PegIFNalpha-2a
Weekly 180µg injection for 48wks
Drug: TMC435 Placebo Ribavirin
Placebo tab/day for 24 wks 1000-1200mg tab twice/day for 48 wks

Detailed Description:

The study is a randomized (study drug assigned by chance), 5-arm, double-blind (neither patient nor physician know the assigned drug name), placebo-controlled trial to compare the efficacy, tolerability and safety of different TMC435 regimens combined with the standard of care (SoC: peginterferon alfa-2a and ribavirin) versus SoC alone in adult treatment-naïve patients (never received treatment for HCV) with chronic genotype 1 hepatitis C virus (HCV) infection. Depending on the treatment arm, patients will receive TMC435 (75 or 150 mg) or placebo capsules for a duration of 12 or 24 weeks. In treatment arms 1 and 2, subjects will receive 12 weeks of triple therapy with TMC435 once daily plus SoC followed by 12 weeks of treatment with SoC plus TMC435-matched placebo. In treatment arms 3 and 4, patients will receive 24 weeks of triple therapy with TMC435 once daily plus SoC. In treatment arm 5 (control group), patients will be treated with SoC treatment for 48 weeks and TMC435-matched placebo for the first 24 weeks. Pegylated interferon is given as a pre-filled syringe containing 0.5 mL solution with 180 µg PegIFNalpha-2a, to be injected under the skin once weekly. 1000-1200mg of Ribavirin, given as 200mg tablets, is taken twice a day with food. The study's objective is to evaluate and compare the efficacy of the treatment arms including TMC435 vs the SoC arm by measuring the proportion of patients with undetectable HCV RNA (< 10 IU/mL) 24 weeks after the planned end of treatment. TMC435 is a 75mg capsule and will be taken orally (via the mouth). Depending on the treatment arm patients will receive TMC435 or placebo for a duration of 12 or 24 weeks. The Standard of Care (SoC) treatment will last 24 or 48 weeks: Pegylated interferon is given as a pre-filled syringe containing 0.5 mL solution with 180 µg pegINFalpha-2a, to be injected under the skin once weekly. Ribavirin is given as 200 mg tablets (daily dose: 1000-1200mg), and taken orally two times a day with food.

  Eligibility

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

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00882908

  Show 71 Study Locations
Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Investigators
Study Director: Tibotec Pharmaceuticals Clinical Trial Tibotec Pharmaceutical Limited
  More Information

No publications provided by Tibotec Pharmaceuticals, Ireland

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Clinical Development Team Leader, Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT00882908     History of Changes
Other Study ID Numbers: CR015799
Study First Received: April 16, 2009
Last Updated: June 28, 2012
Health Authority: United States: Food and Drug Administration
Ireland: Irish Agriculture and Food Development Authority
Canada: Health Canada

Keywords provided by Tibotec Pharmaceuticals, Ireland:
Hepatitis C
Peginterferon alpha-2a
PegIFNalpha-2a
RBV
Ribavirin
Placebo

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

ClinicalTrials.gov processed this record on April 16, 2014