A Safety and Effectiveness Study of TMC435 in Chronic, Genotype 1, Hepatitis C Patients Who Failed to Previous Standard Treatment (ASPIRE)

May 30, 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 PegIFNa-2a and Ribavirin in HCV Genotype 1 Infected Subjects Who Failed Previous Standard Therapy

The purpose of this study is to determine the efficacy, safety and tolerability of different regimens of TMC435 with standard treatment compared to standard treatment alone in participants with chronic, genotype 1, hepatitis C virus (HCV) infection who has failed previous treatment with pegylated interferon (Peg-INF-alfa-2a) and ribavirin (RBV).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study is a randomized (study drug assigned by chance), double-blind (neither physician nor participant knows the name of the assigned drug), placebo-controlled Phase IIb trial with TMC435 in participants with chronic, genotype 1, hepatitis C virus (HCV) infection who have failed standard treatment with pegylated interferon (Peg-INF-alfa-2a) and ribavirin (RBV). The study will compare the efficacy, tolerability and safety of different regimens with TMC435 combined with standard treatment (Peg-INF-alfa-2a and RBV) versus standard treatment alone. The trial will consist of a screening period of maximum 6 weeks, a 48-week treatment period, and a 24-week follow-up period. Participants will be eligible to enroll in the trial if they failed to respond to a prior course of standard treatment or relapsed following standard treatment. Participants will be randomly assigned to receive TMC435 with standard treatment for 12 weeks followed by standard treatment (plus placebo) for 36 weeks, TMC435 (100 mg or 150 mg once a day) with standard treatment for 24 weeks followed by standard treatment (plus placebo) for 24 weeks, TMC435 (100 mg or 150 mg once a day) with standard treatment for 48 weeks, or a placebo with standard treatment for 48 weeks.

Study Type

Interventional

Enrollment (Actual)

463

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
      • New Lambton Heights, Australia
      • Parkville, 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
      • Ottawa, Ontario, Canada
      • Toronto, Ontario, Canada
    • Quebec
      • Montreal, Quebec, Canada
  • France
      • Creteil N/A, France
      • Grenoble, France
      • Lyon, France
      • Nice, France
      • Paris, France
      • Paris Cedex 12, France
      • Vandoeuvre Les Nancy, France
  • Germany
      • Berlin, Germany
      • Düsseldorf, Germany
      • Frankfurt A. M., Germany
      • Freiburg, Germany
      • Hannover, Germany
      • Köln, Germany
      • Stuttgart, Germany
      • Würzburg, Germany
  • Israel
      • Haifa, Israel
      • Jerusalem, Israel
      • Nazareth, Israel
      • Petah Tiqva, Israel
      • Ramat-Gan, Israel
      • Tel-Aviv, Israel
      • Zefat, Israel
  • New Zealand
      • Auckland, New Zealand
      • Christchurch, New Zealand
      • Hamilton, New Zealand
  • Norway
      • Nordbyhagen, Norway
      • Oslo, Norway
      • Tromsø, Norway
  • Poland
      • Bialystok, Poland
      • Bydgoszcz, Poland
      • Czeladz, Poland
      • Kielce, Poland
      • Warszawa, Poland
  • Portugal
      • Coimbra, Portugal
      • Lisboa, Portugal
      • Porto, Portugal
  • Russian Federation
      • Moscow, Russian Federation
      • Nizhny Novgorod, Russian Federation
      • Saint-Petersburg, Russian Federation
      • Samara, Russian Federation
      • Smolensk, Russian Federation
      • St Petersburg, Russian Federation
  • United Kingdom
      • London, United Kingdom
      • Plymouth, United Kingdom
  • United States
    • California
      • La Jolla, California, United States
      • Los Angeles, California, United States
    • Florida
      • Jacksonville, Florida, United States
      • Miami, Florida, United States
      • Orlando, Florida, United States
      • Palm Harbor, Florida, United States
    • Illinois
      • Chicago, Illinois, United States
    • Louisiana
      • New Orleans, Louisiana, United States
    • Maryland
      • Laurel, Maryland, United States
    • Mississippi
      • Jackson, Mississippi, United States
      • Tupelo, Mississippi, 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
      • Nashville, Tennessee, United States
    • Texas
      • San Antonio, Texas, 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:

  • Must have chronic hepatitis C infection as evidenced by liver biopsy, anti-hepatitis C virus (HCV) and HCV RNA positive
  • Must have chronic hepatitis C infection (genotype 1) with HCV RNA level greater than10000 IU/mL
  • Patient must have failed at least 1 prior course of peg interferon (Peg-IFN-alfa-2a)/ribavirin (RBV) therapy (standard treatment)
  • Must be willing to use 2 effective methods of birth control for up to 7 months after last dose of study medication

Exclusion Criteria:

  • Has an evidence of decompensated liver disease
  • Co-infection with any other Hepatitis C virus genotype or co-infection with the human immunodeficiency virus (HIV)
  • Has a medical condition which is a contraindication to Peg-INF or RBV therapy
  • Have had 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 100 mg 12 Wks + PR48
Participants will receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks.
Drug: TMC435
One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.
Drug: Placebo
One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.
Drug: Peg-IFN-alfa-2a (P)
180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.
Other Names:
  • PEGASYS
Drug: Ribavirin (R)
1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.
Other Names:
  • COPEGUS
Experimental: TMC435 100 mg 24 Wks + PR48
Participants willl receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks.
Drug: TMC435
One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.
Drug: Placebo
One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.
Drug: Peg-IFN-alfa-2a (P)
180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.
Other Names:
  • PEGASYS
Drug: Ribavirin (R)
1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.
Other Names:
  • COPEGUS
Experimental: TMC435 100 mg 48 Wks + PR48
Participants will receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.
Drug: TMC435
One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.
Drug: Placebo
One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.
Drug: Peg-IFN-alfa-2a (P)
180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.
Other Names:
  • PEGASYS
Drug: Ribavirin (R)
1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.
Other Names:
  • COPEGUS
Experimental: TMC435 150 mg 12 Wks + PR48
Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks.
Drug: TMC435
One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.
Drug: Placebo
One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.
Drug: Peg-IFN-alfa-2a (P)
180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.
Other Names:
  • PEGASYS
Drug: Ribavirin (R)
1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.
Other Names:
  • COPEGUS
Experimental: TMC435 150 mg 24 Wks + PR48
Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks.
Drug: TMC435
One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.
Drug: Placebo
One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.
Drug: Peg-IFN-alfa-2a (P)
180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.
Other Names:
  • PEGASYS
Drug: Ribavirin (R)
1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.
Other Names:
  • COPEGUS
Experimental: TMC435 150 mg 48 Wks + PR48
Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.
Drug: TMC435
One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.
Drug: Peg-IFN-alfa-2a (P)
180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.
Other Names:
  • PEGASYS
Drug: Ribavirin (R)
1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.
Other Names:
  • COPEGUS
Placebo Comparator: Placebo 48 Wks + PR48
Participants will receive Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.
Drug: TMC435
One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.
Drug: Peg-IFN-alfa-2a (P)
180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.
Other Names:
  • PEGASYS
Drug: Ribavirin (R)
1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.
Other Names:
  • COPEGUS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Percentage of Participants Achieving a Sustained Virologic Response at the End of Treatment (EOT) and 24 Weeks After the EOT (SVR24)
Time Frame: Week 72
The table below shows the percentage of participants in the overall population with an SVR24, defined as having plasma levels of Hepatitis C Virus ribonucleic acid less than 25 IU/mL undetectable at the EOT and 24 weeks after the EOT.
Week 72

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Percentage of Participants With a Greater Than 2 log10 Drop in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Time Points During Treatment
Time Frame: Weeks, 2, 4, 8, and 12
The table below shows the percentage of participants in each treatment group who achieved a greater than 2 log10 drop in plasma levels of HCV RNA at selected time points during treatment.
Weeks, 2, 4, 8, and 12
The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable During Treatment and Follow-up
Time Frame: Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72 and EOT (up to Week 48)
The table below shows the percentage of participants in each treatment who achieved plasma HCV RNA levels of <25 IU/mL undetectable at selected time points during treatment and follow-up and at the end of treatment (EOT).
Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72 and EOT (up to Week 48)
The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Detectable or Undetectable During Treatment and Follow-up
Time Frame: Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and EOT (up to Week 48)
The table below shows the percentage of participants in each treatment group who achieved plasma HCV RNA levels below the limit of quantification defined as less than 25 IU/mL (detectable or undetectable) at selected time points during treatment, follow-up, and at the end of treatment (EOT).
Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and EOT (up to Week 48)
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 an undetectable plasma Hepatitis C virus ribonucleic acid level after receiving 4 weeks of treatment.
Week 4
The Percentage of Participants Achieving an Early Virologic Response (EVR)
Time Frame: Week 12
The table below shows the percentage of participants who achieved an EVR, defined as having a greater than or equal to 2 log10 reduction in plasma Hepatitis C virus ribonucleic acid from baseline at Week 12.
Week 12
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 levels of Hepatitis C virus ribonucleic acid at Week 12.
Week 12
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
Time Frame: Week 60
The table below shows the percentage of participants in the overall population who achieved undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 12 Weeks after the planned EOT.
Week 60
The Percentage of Participants With Viral Breakthrough
Time Frame: EOT (up to Week 48)
The table below shows the percentage of participants in the overall population in each treatment group during the treatment period who experienced viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in Hepatitis C virus (HCV) ribonucleic acid (RNA) from the lowest level reached or a confirmed HCV RNA of > 100 IU/mL in participants whose HCV RNA had previously been below the lower limit of quantification (i.e., less than 25 IU/mL detectable or undetectable).
EOT (up to Week 48)
The Percentage of Participants With Viral Relapse
Time Frame: Up to Week 72
The table below shows the percentage of participants in the overall population who had viral relapse, defined as confirmed detectable Hepatitis C virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with HCV RNA less than 25 IU/mL undetectable at end of treatment.
Up to Week 72
The Number of Participants Who Achieved Normalized Alanine Aminotransferase (ALT) Levels at the End of Treatment (EOT)
Time Frame: EOT (up to Week 48)
The table below shows the number of participants with abnormal ALT levels at Baseline who achieved the normal ALT levels at the EOT (up to Week 48).
EOT (up to Week 48)
Plasma Concentrations of TMC435
Time Frame: 0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48
The table below shows median (range) predose plasma concentration (C0h) values and median (range) average steady-state plasma concentration (Css,av) values for TMC435 for participants in each of the 6 TMC435 treatment groups.
0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
Time Frame: 0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48
The table below shows the median (range) AUC24h values for TMC435 for participants in each TMC435 treatment group.
0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48

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

October 1, 2009

Primary Completion (Actual)

August 1, 2011

Study Completion (Actual)

August 1, 2011

Study Registration Dates

First Submitted

September 10, 2009

First Submitted That Met QC Criteria

September 18, 2009

First Posted (Estimate)

September 21, 2009

Study Record Updates

Last Update Posted (Estimate)

June 9, 2014

Last Update Submitted That Met QC Criteria

May 30, 2014

Last Verified

May 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR016063
  • TMC435-TiDP16-C206 (Other Identifier: Tibotec Pharmaceuticals, Ireland)
  • 2009-010590-20 (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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