Back to resultsA 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)
Primary Purpose
Hepatitis C
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
TMC435
PSI-7977 (GS7977)
Ribavirin
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C focused on measuring Hepatitis C, TMC435, PSI-7977, GS7977, Ribavirin, HCV, Hep C, Genotype 1
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Arm 1
Arm 2
Arm 3
Arm 4
Arm Description
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
Number of Participants With a Sustained Virologic Response (SVR) 12 Weeks After the Planned End of Treatment (EOT)
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) undetectable at end of treatment and HCV RNA less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 12 weeks after the planned end of treatment.
Secondary Outcome Measures
Number of Participants With a Sustained Virologic Response (SVR) 4 Weeks After the Planned End of Treatment (EOT)
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) undetectable at end of treatment and HCV RNA less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 4 weeks after the planned end of treatment.
Number of Participants With a Sustained Virologic Response (SVR) 24 Weeks After the Planned End of Treatment (EOT)
Participants with HCV RNA undetectable at end of treatment and HCV RNA less than (<) 25 IU/mL (detectable or undetectable) at 24 weeks after the planned end of treatment.
Number of Participants With a Sustained Virologic Response (SVR) at Week 48
Participants with HCV RNA undetectable at end of treatment and HCV RNA less than (<) 25 IU/mL (detectable or undetectable) at week 48.
Number of Participants With Viral Breakthrough
Viral breakthrough was defined as confirmed quantifiable HCV RNA after becoming less than (<) lower limit of quantification (LLOQ) or confirmed greater than (>) 1 log10 HCV RNA increase from the lowest level reached on 2 consecutive occasions.
Number of Participants With Inadequate Virologic Response
Inadequate Virologic Response was defined as confirmed detectable HCV RNA at or after Week 8 and not meeting the viral breakthrough definition.
Number of Participants With Viral Relapse
Viral relapse was defined as undetectable HCV RNA at the actual EOT and confirmed quantifiable HCV RNA (>= 25 IU/mL) during follow-up period.
Full Information
NCT ID
NCT01466790
First Posted
November 3, 2011
Last Updated
January 26, 2015
Sponsor
Janssen R&D Ireland
Collaborators
Gilead Sciences
1. Study Identification
Unique Protocol Identification Number
NCT01466790
Brief Title
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
Acronym
COSMOS
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2015
Overall Recruitment Status
Completed
Study Start Date
January 2012 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
January 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen R&D Ireland
Collaborators
Gilead Sciences
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C
Keywords
Hepatitis C, TMC435, PSI-7977, GS7977, Ribavirin, HCV, Hep C, Genotype 1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
168 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm 3
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm 4
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
TMC435
Intervention Description
TMC435 will be administered as one oral capsule of 150 mg once a day.
Intervention Type
Drug
Intervention Name(s)
PSI-7977 (GS7977)
Other Intervention Name(s)
GS7977
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Intervention Description
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).
Primary Outcome Measure Information:
Title
Number of Participants With a Sustained Virologic Response (SVR) 12 Weeks After the Planned End of Treatment (EOT)
Description
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) undetectable at end of treatment and HCV RNA less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 12 weeks after the planned end of treatment.
Time Frame
Week 12 and 24 (for the arms treated for 12 weeks) or Week 24 and 36 (for the arms treated for 24 weeks)
Secondary Outcome Measure Information:
Title
Number of Participants With a Sustained Virologic Response (SVR) 4 Weeks After the Planned End of Treatment (EOT)
Description
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) undetectable at end of treatment and HCV RNA less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 4 weeks after the planned end of treatment.
Time Frame
Week 12 and 16 (for the arms treated for 12 weeks) or Week 24 and 28 (for the arms treated for 24 weeks)
Title
Number of Participants With a Sustained Virologic Response (SVR) 24 Weeks After the Planned End of Treatment (EOT)
Description
Participants with HCV RNA undetectable at end of treatment and HCV RNA less than (<) 25 IU/mL (detectable or undetectable) at 24 weeks after the planned end of treatment.
Time Frame
Week 12 and 36 (for the arms treated for 12 weeks) or Week 24 and 48 (for the arms treated for 24 weeks)
Title
Number of Participants With a Sustained Virologic Response (SVR) at Week 48
Description
Participants with HCV RNA undetectable at end of treatment and HCV RNA less than (<) 25 IU/mL (detectable or undetectable) at week 48.
Time Frame
Week 48
Title
Number of Participants With Viral Breakthrough
Description
Viral breakthrough was defined as confirmed quantifiable HCV RNA after becoming less than (<) lower limit of quantification (LLOQ) or confirmed greater than (>) 1 log10 HCV RNA increase from the lowest level reached on 2 consecutive occasions.
Time Frame
Up to End of Treatment [Week 12 (for the arms treated for 12 weeks) or Week 24 (for the arms treated for 24 weeks)]
Title
Number of Participants With Inadequate Virologic Response
Description
Inadequate Virologic Response was defined as confirmed detectable HCV RNA at or after Week 8 and not meeting the viral breakthrough definition.
Time Frame
Week 8 and End of Treatment [Week 12 (for the arms treated for 12 weeks) or Week 24 (for the arms treated for 24 weeks)]
Title
Number of Participants With Viral Relapse
Description
Viral relapse was defined as undetectable HCV RNA at the actual EOT and confirmed quantifiable HCV RNA (>= 25 IU/mL) during follow-up period.
Time Frame
During the Follow-up [Week 36 (for the arms treated for 12 weeks) or Week 24 (for the arms treated for 24 weeks)]
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen R&D Ireland Clinical Trial
Organizational Affiliation
Janssen R&D Ireland
Official's Role
Study Director
Facility Information:
City
Hoover
State/Province
Alabama
Country
United States
City
Bakersfield
State/Province
California
Country
United States
City
La Jolla
State/Province
California
Country
United States
City
San Diego
State/Province
California
Country
United States
City
New Haven
State/Province
Connecticut
Country
United States
City
Brandenton
State/Province
Florida
Country
United States
City
Jacksonville
State/Province
Florida
Country
United States
City
Orlando
State/Province
Florida
Country
United States
City
Tampa
State/Province
Florida
Country
United States
City
Wellington
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Lutherville
State/Province
Maryland
Country
United States
City
Lebanon
State/Province
New Hampshire
Country
United States
City
New York
State/Province
New York
Country
United States
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Pittsburgh
State/Province
Pennsylvania
Country
United States
City
Arlington
State/Province
Texas
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
City
Falls Church
State/Province
Virginia
Country
United States
City
Norfolk
State/Province
Virginia
Country
United States
City
Seatle
State/Province
Washington
Country
United States
City
Santurce
Country
Puerto Rico
12. IPD Sharing Statement
Citations:
PubMed Identifier
25078309
Citation
Lawitz E, Sulkowski MS, Ghalib R, Rodriguez-Torres M, Younossi ZM, Corregidor A, DeJesus E, Pearlman B, Rabinovitz M, Gitlin N, Lim JK, Pockros PJ, Scott JD, Fevery B, Lambrecht T, Ouwerkerk-Mahadevan S, Callewaert K, Symonds WT, Picchio G, Lindsay KL, Beumont M, Jacobson IM. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study. Lancet. 2014 Nov 15;384(9956):1756-65. doi: 10.1016/S0140-6736(14)61036-9. Epub 2014 Jul 28. Erratum In: Lancet. 2014 Nov 15;384(9956):1748.
Results Reference
derived
Learn more about this trial
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
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