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)

May 19, 2014 updated by: Tibotec Pharmaceuticals, Ireland

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 Peginterferon Alfa-2a and Ribavirin In Treatment-Naive Genotype 1 Hepatitis C-Infected Subjects

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

386

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Concord, Australia
      • Darlinghurst, Australia
      • Fitzroy, Australia
      • Melbourne, Australia
      • Sydney, Australia
      • Woolloongabba N/A, Australia
  • Austria
      • Wien, Austria
  • Belgium
      • Brugge, Belgium
      • Brussels, Belgium
      • Bruxelles, Belgium
      • Edegem, Belgium
      • Gent, Belgium
      • Leuven, Belgium
      • Roeselare, Belgium
  • Canada
    • Alberta
      • Calgary, Alberta, Canada
    • Ontario
      • Toronto, Ontario, Canada
    • Quebec
      • Montreal, Quebec, Canada
  • Denmark
      • Aarhus, Denmark
      • Copenhagen, Denmark
      • Hvidovre N/A, Denmark
      • Kolding, Denmark
      • Odense N/A, Denmark
  • France
      • Clichy, France
      • Creteil N/A, France
      • Grenoble, France
      • Lyon, France
      • Nice, France
      • Paris, France
      • Vandoeuvre Les Nancy, France
  • Germany
      • Berlin, Germany
      • Düsseldorf, Germany
      • Frankfurt A. M., Germany
      • Freiburg, Germany
      • Hamburg, Germany
      • Hannover, Germany
      • Köln, Germany
      • Stuttgart, Germany
      • Würzburg, Germany
  • New Zealand
      • Auckland, New Zealand
      • Christchurch, New Zealand
      • Hamilton, New Zealand
  • Norway
      • Bergen, Norway
      • Nordbyhagen, Norway
      • Oslo, Norway
      • Tromsø, Norway
  • Poland
      • Bialystok, Poland
      • Bydgoszcz, Poland
      • Czeladz, Poland
      • Kielce, Poland
      • Lodz, Poland
      • Warschau, Poland
  • Russian Federation
      • Moscow, Russian Federation
      • Nizhny Novgorod, Russian Federation
      • Saint-Petersburg, Russian Federation
      • Samara, Russian Federation
      • Smolensk, Russian Federation
      • St Petersburg, Russian Federation
  • Spain
      • Barcelona, Spain
      • Madrid, Spain
      • Sevilla N/A, Spain
      • Valencia, Spain
  • United States
    • California
      • Los Angeles, California, United States
    • Florida
      • Jacksonville, Florida, United States
      • Orlando, Florida, United States
      • Palm Harbor, Florida, United States
    • Illinois
      • Chicago, Illinois, United States
    • Louisiana
      • New Orleans, Louisiana, United States
    • Minnesota
      • Saint Paul, Minnesota, United States
    • New York
      • New York, New York, United States
    • North Carolina
      • Chapel Hill, North Carolina, United States
    • Ohio
      • Cincinnati, Ohio, United States
    • Tennessee
      • Germantown, Tennessee, United States
    • Virginia
      • Charlottesville, Virginia, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TMC435 75 mg 12 Wks + PR 24/48
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.
Drug: TMC435
TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.
Other Names:
  • TMC 435
Drug: Ribavirin (R)
Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.
Other Names:
  • COPEGUS
Drug: PegIFNα-2a (P)
PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.
Other Names:
  • PEGASYS
Drug: Placebo
Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
Experimental: TMC435 75 mg 24 Wks + PR 24/48
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.
Drug: TMC435
TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.
Other Names:
  • TMC 435
Drug: Ribavirin (R)
Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.
Other Names:
  • COPEGUS
Drug: PegIFNα-2a (P)
PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.
Other Names:
  • PEGASYS
Drug: Placebo
Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
Experimental: TMC435 150 mg 12 Wks + PR 24/48
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.
Drug: TMC435
TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.
Other Names:
  • TMC 435
Drug: Ribavirin (R)
Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.
Other Names:
  • COPEGUS
Drug: PegIFNα-2a (P)
PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.
Other Names:
  • PEGASYS
Drug: Placebo
Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
Experimental: TMC435 150 mg 24 Wks + PR 24/48
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.
Drug: TMC435
TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.
Other Names:
  • TMC 435
Drug: Ribavirin (R)
Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.
Other Names:
  • COPEGUS
Drug: PegIFNα-2a (P)
PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.
Other Names:
  • PEGASYS
Drug: Placebo
Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
Placebo Comparator: Placebo 24 Wks + PR48
Participants will receive Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Drug: Ribavirin (R)
Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.
Other Names:
  • COPEGUS
Drug: PegIFNα-2a (P)
PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.
Other Names:
  • PEGASYS
Drug: Placebo
Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
Time Frame: Week 72
The table below shows the percentage of participants in each treatment group who achieved a SVRW72, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72.
Week 72

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
Time Frame: Week 4
The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels after receiving 4 weeks of treatment.
Week 4
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
Time Frame: Week 12
The table below shows the percentage of participants in each treatment group who had a cEVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 12.
Week 12
The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Undetectable During Treatment and Follow-up
Time Frame: Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
The table below shows the percentage of participants in each treatment group who achieved plasma HCV RNA levels of less than 25 IU/mL undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT).
Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
The Percentage of Participants Who Achieved Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Detectable or Undetectable During Treatment and Follow-up
Time Frame: Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA less than 25 IU/mL detectable or undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT).
Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Greater Than or Equal to 2 log10 Drop During Treatment
Time Frame: Baseline (Day 1) and Weeks, 2, 4, 8, and 12
The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA greater than or equal to 2 log10 drop from Baseline at selected time points during treatment.
Baseline (Day 1) and Weeks, 2, 4, 8, and 12
The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
Time Frame: Week 48 or 72
The table below shows the percentage of participants in each treatment group who achieved a SVR24, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 24 weeks after the EOT.
Week 48 or 72
The Percentage of Participants Achieving an Early Virologic Response (EVR)
Time Frame: Baseline (Day 1) and Week 12
The table below shows the percentage of participants who achieved an EVR, defined as having a change from baseline in plasma Hepatitis C virus ribonucleic acid of 2 log10 at Week 12.
Baseline (Day 1) and Week 12
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
Time Frame: Up to Week 36 or 52
The table below shows the percentage of participants who achieved undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 12 Weeks after the EOT.
Up to Week 36 or 52
Number of Participants With Viral Breakthrough
Time Frame: Week 24 or 48
The table below shows the number of participants in each treatment group who experienced viral breakthrough during the TMC435 treatment period of the study, defined as a confirmed increase of more than 1 log10 IU/mL in plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached or a confirmed value of plasma HCV RNA more than 100 IU/mL in participants whose plasma HCV RNA level had previously been below the limit of quantification (less than 25 IU/mL detectable or undetectable).
Week 24 or 48
The Number of Participants With Viral Relapse
Time Frame: Up to Week 72
The table below shows the number of participants who experienced viral relapse, defined as a confirmed detectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level during the follow-up period in participants with undetectable plasma HCV RNA (less than 25 IU/mL undetectable) at the end of treatment.
Up to Week 72
The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normalized ALT Levels at the End of Treatment (EOT)
Time Frame: Baseline (Day 1) up to Week 24 or 48
The table below shows the number of participants with abnormal ALT levels at Baseline who achieved ALT levels within the normal range at the EOT.
Baseline (Day 1) up to Week 24 or 48
Plasma Concentrations of TMC435
Time Frame: Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
The table below shows median (range) predose plasma concentration (C0h) values and median (range) average steady-state plasma concentration (Css,av) values for participants in each of the 4 TMC435 treatment groups.
Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
Time Frame: Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
The table below shows the median (range) AUC24h values for TMC435 for participants in each of the 4 TMC435 treatment groups. Two blood samples taken at least 2 hours apart from each other for determination of TMC435 plasma pharmacokinetics were obtained in all participants on Weeks 2, 4, 8, 12, 16, and 24 to obtain Bayesian estimates of TMC435 AUC24h (overall exposure).
Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tibotec Pharmaceuticals, Ireland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2009

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

April 1, 2011

Study Registration Dates

First Submitted

April 16, 2009

First Submitted That Met QC Criteria

April 16, 2009

First Posted (Estimate)

April 17, 2009

Study Record Updates

Last Update Posted (Estimate)

June 16, 2014

Last Update Submitted That Met QC Criteria

May 19, 2014

Last Verified

May 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR015799
  • TMC435-TiDP16-C205 (Other Identifier: Tibotec Pharmaceuticals, Ireland)
  • 2008-007147-13 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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