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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)

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ClinicalTrials.gov Identifier: NCT01466790
Recruitment Status : Completed
First Posted : November 8, 2011
Results First Posted : October 22, 2014
Last Update Posted : February 9, 2015
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Janssen R&D Ireland

Tracking Information
First Submitted Date  ICMJE November 3, 2011
First Posted Date  ICMJE November 8, 2011
Results First Submitted Date  ICMJE October 17, 2014
Results First Posted Date  ICMJE October 22, 2014
Last Update Posted Date February 9, 2015
Study Start Date  ICMJE January 2012
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 17, 2014)
Number of Participants With a Sustained Virologic Response (SVR) 12 Weeks After the Planned End of Treatment (EOT) [ 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) ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 3, 2011)
Proportion of subjects with a sustained virologic response (SVR) 12 weeks after the planned end of treatment. [ Time Frame: 12 weeks after the planned end of treatment (at week 24 for the 12 week treatment duration and at week 36 for the 24 week treatment duration) ]
SVR12 is defined as undetectable HCV RNA (< 25 IU/mL target not detected) at the end of treatment and 12 weeks after the planned end of treatment.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2014)
  • Number of Participants With a Sustained Virologic Response (SVR) 4 Weeks After the Planned End of Treatment (EOT) [ 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) ]
    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) [ 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) ]
    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 [ Time Frame: 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 [ 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)] ]
    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 [ 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)] ]
    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 [ 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)] ]
    Viral relapse was defined as undetectable HCV RNA at the actual EOT and confirmed quantifiable HCV RNA (>= 25 IU/mL) during follow-up period.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis C
Intervention  ICMJE
  • Drug: TMC435
    TMC435 will be administered as one oral capsule of 150 mg once a day.
  • 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).
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: TMC435
    • Drug: PSI-7977 (GS7977)
    • Drug: 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.
    Interventions:
    • Drug: TMC435
    • Drug: PSI-7977 (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.
    Interventions:
    • Drug: TMC435
    • Drug: PSI-7977 (GS7977)
    • Drug: 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.
    Interventions:
    • Drug: TMC435
    • Drug: PSI-7977 (GS7977)
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 25, 2013)
168
Original Estimated Enrollment  ICMJE
 (submitted: November 3, 2011)
180
Actual Study Completion Date  ICMJE January 2014
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01466790
Other Study ID Numbers  ICMJE CR018724
TMC435HPC2002 ( Other Identifier: Janssen R&D Ireland )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen R&D Ireland
Study Sponsor  ICMJE Janssen R&D Ireland
Collaborators  ICMJE Gilead Sciences
Investigators  ICMJE
Study Director: Janssen R&D Ireland Clinical Trial Janssen R&D Ireland
PRS Account Janssen R&D Ireland
Verification Date January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP