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Study to Determine the Effectiveness and Safety of a Three Drug Antiviral Combination Therapy to Treat Hepatitis C Virus (HCV) Infected Patients Not Previously Treated With Currently Available Medications

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01455090
Recruitment Status : Completed
First Posted : October 19, 2011
Last Update Posted : April 27, 2017
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE October 18, 2011
First Posted Date  ICMJE October 19, 2011
Last Update Posted Date April 27, 2017
Actual Study Start Date  ICMJE November 30, 2011
Actual Primary Completion Date March 31, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 18, 2011)
Sustained virologic response (SVR) at 12 weeks post-treatment (SVR12) [ Time Frame: 12 weeks post-treatment ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2012)
  • Proportion of subjects with HCV ribonucleic acid (RNA) < limit of quantification (LOQ) (detectable and undetectable) [ Time Frame: Weeks 1, 2, 4, 6, 8, 10, 12,14, 16, 18, 20, 22 and 24 weeks of therapy; at end of treatment (EOT) (following 12 or 24 weeks of treatment, by Group); and Weeks 4, 12, 24, 36, and 48 weeks post-treatment ]
  • Proportion of subjects with HCV ribonucleic acid (RNA) undetectable [ Time Frame: Weeks 1, 2, 4, 6, 8, 10, 12,14, 16, 18, 20, 22 and 24 weeks of therapy; at end of treatment (EOT) (following 12 or 24 weeks of treatment, by Group); and Weeks 4, 12, 24, 36, and 48 weeks post-treatment ]
  • Proportion of subjects who experience viral breakthrough [ Time Frame: Formal analysis at SVR12, Week 48 of follow up period (or upon occurrence) ]
    viral breakthrough defined as:
    • Any increase in HCV RNA ≥ 1 log10 from nadir or
    • Any quantifiable HCV RNA ≥ 25 IU/mL (> LOQ) on or after Week 8
  • Proportion of subjects who experience viral relapse defined as confirmed quantifiable HCV RNA ≥ 25 IU/mL (>LOQ) in a subject with HCV RNA < LOQ or undetectable at End of treatment (EOT) [ Time Frame: End of treatment (Maximum up to 24 Weeks) ]
  • Maximum observed plasma concentration (Cmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [ Time Frame: Day 1 and Day 14 ]
  • Observed plasma concentration at 12 hours (C12) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [ Time Frame: Day 1 and Day 14 ]
  • Observed plasma concentration at 24 hours (C24) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [ Time Frame: Day 1 and Day 14 ]
  • Trough observed plasma concentration (Ctrough) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [ Time Frame: Day 1 and Day 14 ]
  • Time of maximum observed plasma concentration (Tmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [ Time Frame: Day 1 and Day 14 ]
  • Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [ Time Frame: Day 1 and Day 14 ]
  • HCV genomic substitutions associated with exposure of BMS-650032, BMS-790052, and BMS-791325 [ Time Frame: At the time of viral breakthrough or relapse ]
  • Frequency of deaths, serious adverse events (SAEs), discontinuations due to adverse events (AEs), severity Grade 3/4 AEs, and severity Grade 3/4 laboratory abnormalities [ Time Frame: Formal analysis at week 48 of follow up period (or upon occurrence) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2011)
  • Proportion of subjects with HCV ribonucleic acid (RNA) < limit of quantification (LOQ) (detectable and undetectable) [ Time Frame: Weeks 1, 2, 4, 6, 8, 10, 12,14, 16, 18, 20, 22 and 24 weeks of therapy; at end of treatment (EOT) (following 12 or 24 weeks of treatment, by Group); and Weeks 4, 12, 24, 36, and 48 weeks post-treatment ]
  • Proportion of subjects with HCV ribonucleic acid (RNA) < limit of detection (LOD) (detectable and undetectable) [ Time Frame: Weeks 1, 2, 4, 6, 8, 10, 12,14, 16, 18, 20, 22 and 24 weeks of therapy; at end of treatment (EOT) (following 12 or 24 weeks of treatment, by Group); and Weeks 4, 12, 24, 36, and 48 weeks post-treatment ]
  • Proportion of subjects who experience viral breakthrough [ Time Frame: Formal analysis at SVR12, Week 48 of follow up period (or upon occurrence) ]
    viral breakthrough defined as:
    • Any increase in HCV RNA ≥ 1 log10 from nadir or
    • Any quantifiable HCV RNA ≥ 25 IU/mL (> LOQ) on or after Week 8
  • Proportion of subjects who experience viral relapse defined as confirmed detectable HCV RNA in a subject with HCV RNA undetectable (or unconfirmed detectable HCV RNA [< 25 IU/mL]) [ Time Frame: End of treatment ]
  • Maximum observed plasma concentration (Cmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [ Time Frame: Day 14 ]
  • Trough observed plasma concentration (Cmin) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [ Time Frame: Day 14 ]
  • Time of maximum observed plasma concentration (Tmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [ Time Frame: Day 14 ]
  • Area under the concentration-time curve in one dosing interval (AUC(TAU)) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [ Time Frame: Day 14 ]
  • HCV genomic substitutions associated with exposure of BMS-650032, BMS-790052, and BMS-791325 [ Time Frame: At the time of viral breakthrough or relapse ]
  • Frequency of deaths, SAEs, discontinuations due to AEs, severity Grade 3/4 AEs, and severity Grade 3/4 laboratory abnormalities [ Time Frame: Formal analysis at week 48 of follow up period (or upon occurrence) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Determine the Effectiveness and Safety of a Three Drug Antiviral Combination Therapy to Treat Hepatitis C Virus (HCV) Infected Patients Not Previously Treated With Currently Available Medications
Official Title  ICMJE Open-Label, Multiple-Dose, Dose Escalation Study to Evaluate the Pharmacodynamics, Pharmacokinetics, and Safety of Coadministration of BMS-650032, BMS-790052, and BMS-791325 When Administered for 24 or 12 Weeks in Treatment-Naïve Subjects Infected With Hepatitis C Virus Genotype 1
Brief Summary The purpose of this study is to estimate the rate of sustained virologic response (SVR) SVR12, where SVR12 is defined as HCV RNA < LOQ (detectable or undetectable) 12 weeks post-treatment in Genotype 1 & Genotype 4 treatment naive patients, and Genotype (GT1) infected patients who are prior null responders to pegIFN/ribavirin
Detailed Description IND numbers: 79,599; 101,943
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 Chronic Hepatitis C
Intervention  ICMJE
  • Drug: BMS-650032
    Other Name: Asunaprevir (ASV)
  • Drug: BMS-790052
    Other Name: Daclatasvir (DCV)
  • Drug: BMS-791325
  • Drug: Ribavirin
    Other Name: Copegus®
Study Arms  ICMJE
  • Experimental: Group 1:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)

    BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks

    BMS-790052 60 mg tablet by mouth once daily for 24 Weeks

    BMS 791325 75 mg table by mouth twice daily for 24 Weeks

    Interventions:
    • Drug: BMS-650032
    • Drug: BMS-790052
    • Drug: BMS-791325
  • Experimental: Group 2:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)

    BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks

    BMS-790052 60 mg tablet by mouth once daily for 12 Weeks

    BMS 791325 75 mg table by mouth twice daily for 12 Weeks

    Interventions:
    • Drug: BMS-650032
    • Drug: BMS-790052
    • Drug: BMS-791325
  • Experimental: Group 3:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)

    * Contingent upon review of safety data from all available treated subjects from Groups 1 and 2

    BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks

    BMS-790052 60 mg tablet by mouth once daily for 24 Weeks

    BMS 791325 150 mg table by mouth twice daily for 24 Weeks

    Interventions:
    • Drug: BMS-650032
    • Drug: BMS-790052
    • Drug: BMS-791325
  • Experimental: Group 4:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)

    * Contingent upon review of safety data from all available treated subjects from Groups 1 and 2

    BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks

    BMS-790052 60 mg tablet by mouth once daily for 12 Weeks

    BMS 791325 150 mg table by mouth twice daily for 12 Weeks

    Interventions:
    • Drug: BMS-650032
    • Drug: BMS-790052
    • Drug: BMS-791325
  • Experimental: Group 5:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)

    * Genotype 1 treatment-naive subjects

    BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks

    BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks

    BMS 791325 75 mg table by mouth twice daily for 12 Weeks

    Interventions:
    • Drug: BMS-650032
    • Drug: BMS-790052
    • Drug: BMS-791325
  • Experimental: Group 6:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)

    * Genotype 1 treatment-naive subjects

    BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks

    BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks

    BMS 791325 150 mg table by mouth twice daily for 12 Weeks

    Interventions:
    • Drug: BMS-650032
    • Drug: BMS-790052
    • Drug: BMS-791325
  • Experimental: Group 7:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)

    * Genotype 4 treatment-naive subjects

    BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks

    BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks

    BMS 791325 75 mg table by mouth twice daily for 12 Weeks

    Interventions:
    • Drug: BMS-650032
    • Drug: BMS-790052
    • Drug: BMS-791325
  • Experimental: Group 8:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)

    * Genotype 4 treatment-naive subjects

    BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks

    BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks

    BMS 791325 150 mg table by mouth twice daily for 12 Weeks

    Interventions:
    • Drug: BMS-650032
    • Drug: BMS-790052
    • Drug: BMS-791325
  • Experimental: Group 9:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)

    * Genotype 1 treatment-null/non-responder subjects

    BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks

    BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks

    BMS 791325 75 mg table by mouth twice daily for 12 Weeks

    Interventions:
    • Drug: BMS-650032
    • Drug: BMS-790052
    • Drug: BMS-791325
  • Experimental: Group10:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)

    * Genotype 1 treatment-null/non-responder subjects

    BMS-650032 200 mg tablet by mouth twice daily for 12 Weeks

    BMS-790052 30 mg tablet by mouth twice daily for 12 Weeks

    BMS 791325 150 mg table by mouth twice daily for 12 Weeks

    Interventions:
    • Drug: BMS-650032
    • Drug: BMS-790052
    • Drug: BMS-791325
  • Experimental: Group11:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)

    * Genotype 1 treatment-null/non-responder subjects

    BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks

    BMS-790052 30 mg tablet by mouth twice daily for 24 Weeks

    BMS 791325 75 mg table by mouth twice daily for 24 Weeks

    Interventions:
    • Drug: BMS-650032
    • Drug: BMS-790052
    • Drug: BMS-791325
  • Experimental: Group12:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)

    * Genotype 1 treatment-null/non-responder subjects

    BMS-650032 200 mg tablet by mouth twice daily for 24 Weeks

    BMS-790052 30 mg tablet by mouth twice daily for 24 Weeks

    BMS 791325 150 mg table by mouth twice daily for 24 Weeks

    Interventions:
    • Drug: BMS-650032
    • Drug: BMS-790052
    • Drug: BMS-791325
  • Experimental: Grp13:BMS-650032(200mg)+BMS-790052(30mg)+BMS-791325(75mg)+RBV

    * Genotype 1 treatment-naive subjects

    BMS-650032 200 mg tablets orally twice daily 12 weeks

    BMS-790052 30 mg tablets orally twice daily 12 weeks

    BMS-791325 75 mg tablets orally twice daily 12 weeks

    Ribavirin (RBV) tablets orally weight based dosing daily 12 weeks [if subject is < 75 kg: 1000 mg per day orally (2 x 200 mg tablets in AM and 3 x 200 mg tablets in PM), or if ≥ 75 kg: 1200 mg per day orally (3 x 200 mg tablets in AM and 3 x 200 mg tablets in PM]

    Interventions:
    • Drug: BMS-650032
    • Drug: BMS-790052
    • Drug: BMS-791325
    • Drug: Ribavirin
Publications *

*   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: September 10, 2015)
320
Original Estimated Enrollment  ICMJE
 (submitted: October 18, 2011)
64
Actual Study Completion Date  ICMJE July 31, 2015
Actual Primary Completion Date March 31, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Men and women, ages ≥18 years of age
  • Subjects who are naive to HCV treatment, defined as no previous exposure to an Interferon (IFN), Ribavirin (RBV); or any HCV-specific direct acting antiviral or experimental therapy or subjects who are null responders to previous pegylated Interferon alfa (pegIFNα) plus Ribavirin (RBV) treatment
  • Subjects should have chronic hepatitis C (CHC) as documented by:

    1. Positive for anti-HCV antibody, HCV RNA, or a positive HCV genotype test at least 6 months prior to screening, and positive for HCV RNA and Anti-HCV antibody at the time of screening, or
    2. Positive for anti-HCV antibody and HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed prior to enrollment with evidence of CHC disease, such as the presence of fibrosis)
  • HCV genotype 1a, 1b or 4 only
  • HCV RNA viral load of ≥10,000 IU/mL at screening
  • Have one of the following:

    1. Documented Fibrotest score of ≤0.72 and aspartate transferase (transminase) to platelet ratio index (APRI) ≤2; OR
    2. Documented liver biopsy within 36 months preceding Day 1 showing absence of cirrhosis OR
    3. Documented Fibroscan® ultrasound (where approved) within 12 months of screening showing absence of cirrhosis
  • Body mass index (BMI) of 18.0 to 35.0 kg/m2, inclusive
  • Subjects with compensated Child-Pugh A cirrhosis as documented by history of cirrhosis with any prior liver biopsy or Fibroscan® ultrasound (where approved) within 12 months prior to screening

Exclusion Criteria:

  • Evidence of a medical condition associated with chronic liver disease other than HCV (such as but not limited to: hemochromatosis, autoimmune hepatitis,metabolic liver disease, alcoholic liver disease, toxin exposures)
  • History of variceal bleeding, hepatic encephalopathy, or ascites requiring management with diuretics or paracentesis
  • Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment
  • Documented or suspected hepatocellular carcinoma (HCC)
  • Positive for hepatitis B surface antigen (HBsAg)
  • Positive for Human Immunodeficiency Virus-1 (HIV-1) and/or Human Immunodeficiency Virus-2 (HIV-2) antibodies
  • Alanine transferase (transminase) (ALT) >5x upper limit of normal (ULN)
  • Total Bilirubin ≥2 mg/dL
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (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 France,   Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01455090
Other Study ID Numbers  ICMJE AI443-014
2011-002788-11 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Bristol-Myers Squibb
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Bristol-Myers Squibb
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date April 2017

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