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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00980330
First received: September 10, 2009
Last updated: May 30, 2014
Last verified: May 2014
  Purpose

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).


Condition Intervention Phase
Hepatitis C
Drug: TMC435
Drug: Placebo
Drug: Peg-IFN-alfa-2a (P)
Drug: Ribavirin (R)
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 PegIFNa-2a and Ribavirin in HCV Genotype 1 Infected Subjects Who Failed Previous Standard Therapy

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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).

  • 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) ] [ Designated as safety issue: No ]
    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).

  • The Percentage of Participants Achieving a Rapid Virologic Response (RVR) [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    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.

  • The Percentage of Participants Achieving an Early Virologic Response (EVR) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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.

  • The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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.

  • The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) [ Time Frame: Week 60 ] [ Designated as safety issue: No ]
    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.

  • The Percentage of Participants With Viral Breakthrough [ Time Frame: EOT (up to Week 48) ] [ Designated as safety issue: No ]
    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).

  • The Percentage of Participants With Viral Relapse [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
    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.

  • The Number of Participants Who Achieved Normalized Alanine Aminotransferase (ALT) Levels at the End of Treatment (EOT) [ Time Frame: EOT (up to Week 48) ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    The table below shows the median (range) AUC24h values for TMC435 for participants in each TMC435 treatment group.


Enrollment: 463
Study Start Date: October 2009
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: COPEGUS

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00980330

  Show 81 Study Locations
Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Investigators
Study Director: Tibotec Pharmaceuticals, Ireland Clinical Trial Tibotec Pharmaceuticals, Ireland
  More Information

No publications provided by Tibotec Pharmaceuticals, Ireland

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT00980330     History of Changes
Other Study ID Numbers: CR016063, TMC435-TiDP16-C206, 2009-010590-20
Study First Received: September 10, 2009
Results First Received: December 18, 2013
Last Updated: May 30, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Portugal: National Pharmacy and Medicines Institute
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Israel: Ministry of Health
New Zealand: Medsafe
Norway: Norwegian Medicines Agency
Poland: The Central Register of Clinical Trials
Russia: Ministry of Health of the Russian Federation
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Great Britain: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Tibotec Pharmaceuticals, Ireland:
Hepatitis C
Peginterferon alpha-2a
PegIFNalpha-2a
RBV
Ribavirin
Placebo
TMC435-TIDP16-C206
TMC435-C206
TMC435
HCV

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
Interferon Alfa-2a
Interferon-alpha
Ribavirin
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Immunologic Factors
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014