A Study of TMC435 in Combination With PSI-7977 (GS7977) in Chronic Hepatitis C Genotype 1-Infected Prior Null Responders To Peginterferon/Ribavirin Therapy or HCV Treatment-Naive Patients (COSMOS)

This study has been completed.
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Janssen R&D Ireland
ClinicalTrials.gov Identifier:
NCT01466790
First received: November 3, 2011
Last updated: February 25, 2014
Last verified: February 2014
  Purpose

The purpose of this study is to investigate the efficacy and safety of TMC435 plus PSI-7977 (GS7977) with or without ribavirin in patients who are chronically infected with genotype 1 hepatitis C virus (HCV) and who did not respond to prior peginterferon/ribavirin therapy or are HCV treatment-naive (patients who never received treatment for HCV infection).


Condition Intervention Phase
Hepatitis C
Drug: TMC435
Drug: PSI-7977 (GS7977)
Drug: Ribavirin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Exploratory Phase IIa, Randomized, Open-Label Trial to Investigate the Efficacy and Safety of 12 Weeks or 24 Weeks of TMC435 in Combination With PSI-7977 (GS7977) With Or Without Ribavirin in Chronic Hepatitis C Genotype 1-Infected Prior Null Responders To Peginterferon/Ribavirin Therapy or HCV Treatment-Naive Subjects

Resource links provided by NLM:


Further study details as provided by Janssen R&D Ireland:

Primary Outcome Measures:
  • Number of patients with a sustained virologic response (SVR) 12 Weeks after the planned end of treatment [ Time Frame: Week 24 (for the 12 Week treatment duration) and Week 36 (for the 24 Week treatment duration) ] [ Designated as safety issue: No ]
    SVR12 is defined as undetectable Hepatitis C virus (HCV) ribonucleic acid (RNA) 12 Weeks after the planned end of treatment.


Secondary Outcome Measures:
  • Number of patients with a SVR 4 Weeks after the planned end of treatment [ Time Frame: Week 16 (for the 12 Week treatment duration) and Week 28 (for the 24 Week treatment duration) ] [ Designated as safety issue: No ]
  • Number of patients with a SVR at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Number of patients with undetectable HCV RNA [ Time Frame: Week -6, Week 1, Week 2, Week 3, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, Week 16, Week 18, Week 20, Week 22, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48 ] [ Designated as safety issue: No ]
  • Number of patients with viral breakthrough [ Time Frame: Week -6, Week 1, Week 2, Week 3, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, Week 16, Week 18, Week 20, Week 22, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48 ] [ Designated as safety issue: No ]
  • Number of patients with inadequate virologic response [ Time Frame: Week -6, Week 1, Week 2, Week 3, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, Week 16, Week 18, Week 20, Week 22, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48 ] [ Designated as safety issue: No ]
  • Number of patients with viral relapse [ Time Frame: Week -6, Week 1, Week 2, Week 3, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, Week 16, Week 18, Week 20, Week 22, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48 ] [ Designated as safety issue: No ]
  • Number of patients with adverse events [ Time Frame: Up to Week 48 ] [ Designated as safety issue: Yes ]

Enrollment: 168
Study Start Date: January 2012
Study Completion Date: January 2014
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
30 patients will receive TMC435 (150 mg once a day) plus PSI-7977(GS7977) (400 mg once a day) with ribavirin (1000-1200 mg/day) for 24 weeks and followed by a 24-week follow-up phase.
Drug: TMC435
TMC435 will be administered as one oral capsule of 150 mg once a day.
Other Name: TMC435
Drug: PSI-7977 (GS7977)
PSI-7977 (GS7977) will be administered as oral tablets (2 tablets of 200 mg for Cohort 1 and 1 tablet of 400 mg for Cohort 2) once a day.
Other Name: GS7977
Drug: Ribavirin
Ribavirin will be administered according to body weight. For patients with body weight less than 75 kg daily dose (1000 mg) will be administered as 400 mg (2 oral tablets of 200 mg) in the morning and 600 mg (3 oral tablets of 200 mg) in the evening. Body weight more than or equal to 75 kg daily dose (1200 mg) will be administered as 600 mg twice a day (3 tablets of 200 mg per intake, morning and evening).
Other Name: Ribavirin
Experimental: Arm 2
15 patients wiil receive TMC435 (150 mg once a day) plus PSI-7977 (GS7977) (400 mg once a day) for 24 weeks of and followed by a 24-week follow-up phase.
Drug: TMC435
TMC435 will be administered as one oral capsule of 150 mg once a day.
Other Name: TMC435
Drug: PSI-7977 (GS7977)
PSI-7977 (GS7977) will be administered as oral tablets (2 tablets of 200 mg for Cohort 1 and 1 tablet of 400 mg for Cohort 2) once a day.
Other Name: GS7977
Experimental: Arm 3
30 patients will receive TMC435 (150 mg once a day) plus PSI-7977 (GS7977) (400 mg once a day) with ribavirin (1000-1200 mg/day) for 12 weeks and followed by a 36-week follow-up phase.
Drug: TMC435
TMC435 will be administered as one oral capsule of 150 mg once a day.
Other Name: TMC435
Drug: PSI-7977 (GS7977)
PSI-7977 (GS7977) will be administered as oral tablets (2 tablets of 200 mg for Cohort 1 and 1 tablet of 400 mg for Cohort 2) once a day.
Other Name: GS7977
Drug: Ribavirin
Ribavirin will be administered according to body weight. For patients with body weight less than 75 kg daily dose (1000 mg) will be administered as 400 mg (2 oral tablets of 200 mg) in the morning and 600 mg (3 oral tablets of 200 mg) in the evening. Body weight more than or equal to 75 kg daily dose (1200 mg) will be administered as 600 mg twice a day (3 tablets of 200 mg per intake, morning and evening).
Other Name: Ribavirin
Experimental: Arm 4
15 patients will receive TMC435 (150 mg once a day) plus PSI-7977 (GS7977) (400 mg once a day) for 12 weeks and followed by a 36-week follow-up phase.
Drug: TMC435
TMC435 will be administered as one oral capsule of 150 mg once a day.
Other Name: TMC435
Drug: PSI-7977 (GS7977)
PSI-7977 (GS7977) will be administered as oral tablets (2 tablets of 200 mg for Cohort 1 and 1 tablet of 400 mg for Cohort 2) once a day.
Other Name: GS7977

Detailed Description:

This is a Phase IIa, randomized (the study medications are assigned by chance), open label (all people know the identity of the intervention) study of TMC435 plus PSI-7977 (GS7977) with or without ribavirin. The study consists of a screening phase (6 weeks); a treatment phase (12 or 24 week period); and a posttreatment phase (follow-up period up to Week 48). Approximately 180 patients will be enrolled in this study. Patients will be sequentially enrolled into two cohorts in this study. Cohort 1 (90 patients) will include patients without advanced hepatic fibrosis who did not respond to previous PegIFN/ribavirin therapy and Cohort 2 (90 patients) will include only patients with advanced hepatic fibrosis who did not respond to previous PegIFN/ribavirin therapy or are HCV treatment-naive. Safety will be evaluated throughout the study and will include evaluations of adverse events, clinical laboratory tests, electrocardiogram, vital signs, and physical examination. The entire study duration for each participant will be approximately 48 weeks.

  Eligibility

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

Inclusion Criteria:

  • Chronic genotype 1 hepatitis C virus (HCV) infection
  • Plasma HCV RNA of more than 10,000 IU/mL at screening
  • Patients in Cohort 1 must be null responders to PegIFN/ribavirin with at least 1 documented previous course of PegIFN/ribavirin therapy for at least 12 consecutive weeks
  • Patients in Cohort 2 must be null responders to PegIFN/ribavirin with at least 1 documented previous course of PegIFN/ribavirin therapy for at least 12 consecutive weeks and could also be HCV treatment-naive, meaning never received treatment with any approved or investigational drug for the treatment of HCV
  • Null responders patients in Cohort 1 and Cohort 2 must meet the defined criterion for a null responder, defined as on-treatment less than 2 log10 IU/mL reduction in HCV RNA from baseline at Week 12 of the most recent PegIFN/ribavirin therapy
  • Patient must have had a liver biopsy within 3 years before screening (or between screening and baseline visit) or patient must have had a liver biopsy at any time in the past which showed Metavir F3 or F4 fibrosis
  • Must agree to use 2 forms of effective contraception throughout the study (male and female)

Exclusion Criteria:

  • Has evidence of hepatic decompensation
  • Has any liver disease of non-HCV etiology
  • Has an infection/co-infection with non-genotype 1 HCV
  • Has a co-infection with Human immunodeficiency virus (HIV) type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibody test at screening)
  • Has a co-infection with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive)
  • Has a history of malignancy within 5 years of the screening visit
  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: NCT01466790

  Show 23 Study Locations
Sponsors and Collaborators
Janssen R&D Ireland
Gilead Sciences
Investigators
Study Director: Janssen R&D Ireland Clinical Trial Janssen R&D Ireland
  More Information

No publications provided

Responsible Party: Janssen R&D Ireland
ClinicalTrials.gov Identifier: NCT01466790     History of Changes
Other Study ID Numbers: CR018724, TMC435HPC2002
Study First Received: November 3, 2011
Last Updated: February 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Janssen R&D Ireland:
Hepatitis C
TMC435
PSI-7977
GS7977
Ribavirin
HCV
Hep C
Genotype 1

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

ClinicalTrials.gov processed this record on September 18, 2014