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
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
2 other identifiers
interventional
168
2 countries
23
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jan 2012
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 3, 2011
CompletedFirst Posted
Study publicly available on registry
November 8, 2011
CompletedStudy Start
First participant enrolled
January 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2014
CompletedResults Posted
Study results publicly available
October 22, 2014
CompletedFebruary 9, 2015
January 1, 2015
1.8 years
November 3, 2011
October 17, 2014
January 26, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
Week 12 and 24 (for the arms treated for 12 weeks) or Week 24 and 36 (for the arms treated for 24 weeks)
Secondary Outcomes (6)
Number of Participants With a Sustained Virologic Response (SVR) 4 Weeks After the Planned End of Treatment (EOT)
Week 12 and 16 (for the arms treated for 12 weeks) or Week 24 and 28 (for the arms treated for 24 weeks)
Number of Participants With a Sustained Virologic Response (SVR) 24 Weeks After the Planned End of Treatment (EOT)
Week 12 and 36 (for the arms treated for 12 weeks) or Week 24 and 48 (for the arms treated for 24 weeks)
Number of Participants With a Sustained Virologic Response (SVR) at Week 48
Week 48
Number of Participants With Viral Breakthrough
Up to End of Treatment [Week 12 (for the arms treated for 12 weeks) or Week 24 (for the arms treated for 24 weeks)]
Number of Participants With Inadequate Virologic Response
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)]
- +1 more secondary outcomes
Study Arms (4)
Arm 1
EXPERIMENTAL30 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 2
EXPERIMENTAL15 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 3
EXPERIMENTAL30 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 4
EXPERIMENTAL15 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.
Interventions
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.
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).
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Janssen R&D Irelandlead
- Gilead Sciencescollaborator
Study Sites (23)
Unknown Facility
Hoover, Alabama, United States
Unknown Facility
Bakersfield, California, United States
Unknown Facility
La Jolla, California, United States
Unknown Facility
San Diego, California, United States
Unknown Facility
New Haven, Connecticut, United States
Unknown Facility
Brandenton, Florida, United States
Unknown Facility
Jacksonville, Florida, United States
Unknown Facility
Orlando, Florida, United States
Unknown Facility
Tampa, Florida, United States
Unknown Facility
Wellington, Florida, United States
Unknown Facility
Atlanta, Georgia, United States
Unknown Facility
Chicago, Illinois, United States
Unknown Facility
Lutherville, Maryland, United States
Unknown Facility
Lebanon, New Hampshire, United States
Unknown Facility
New York, New York, United States
Unknown Facility
Pittsburgh, Pennsylvania, United States
Unknown Facility
Arlington, Texas, United States
Unknown Facility
Dallas, Texas, United States
Unknown Facility
San Antonio, Texas, United States
Unknown Facility
Falls Church, Virginia, United States
Unknown Facility
Norfolk, Virginia, United States
Unknown Facility
Seatle, Washington, United States
Unknown Facility
Santurce, Puerto Rico
Related Publications (1)
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.
PMID: 25078309DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Leader
- Organization
- Janssen Research & Development, LLC
Study Officials
- STUDY DIRECTOR
Janssen R&D Ireland Clinical Trial
Janssen R&D Ireland
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 3, 2011
First Posted
November 8, 2011
Study Start
January 1, 2012
Primary Completion
November 1, 2013
Study Completion
January 1, 2014
Last Updated
February 9, 2015
Results First Posted
October 22, 2014
Record last verified: 2015-01