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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

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT01455090
Collaborator
(none)
320
Enrollment
32
Locations
13
Arms
44
Actual Duration (Months)
10
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

IND numbers: 79,599; 101,943

Study Design

Study Type:
Interventional
Actual Enrollment :
320 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Nov 30, 2011
Actual Primary Completion Date :
Mar 31, 2014
Actual Study Completion Date :
Jul 31, 2015

Arms and Interventions

Arm Intervention/Treatment
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

Drug: BMS-650032
Other Names:
  • Asunaprevir (ASV)

    • Drug: BMS-790052
    Other Names:
  • Daclatasvir (DCV)

    • 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

    Drug: BMS-650032
    Other Names:
  • Asunaprevir (ASV)

    • Drug: BMS-790052
    Other Names:
  • Daclatasvir (DCV)

    • 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

    Drug: BMS-650032
    Other Names:
  • Asunaprevir (ASV)

    • Drug: BMS-790052
    Other Names:
  • Daclatasvir (DCV)

    • 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

    Drug: BMS-650032
    Other Names:
  • Asunaprevir (ASV)

    • Drug: BMS-790052
    Other Names:
  • Daclatasvir (DCV)

    • 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

    Drug: BMS-650032
    Other Names:
  • Asunaprevir (ASV)

    • Drug: BMS-790052
    Other Names:
  • Daclatasvir (DCV)

    • 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

    Drug: BMS-650032
    Other Names:
  • Asunaprevir (ASV)

    • Drug: BMS-790052
    Other Names:
  • Daclatasvir (DCV)

    • 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

    Drug: BMS-650032
    Other Names:
  • Asunaprevir (ASV)

    • Drug: BMS-790052
    Other Names:
  • Daclatasvir (DCV)

    • 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

    Drug: BMS-650032
    Other Names:
  • Asunaprevir (ASV)

    • Drug: BMS-790052
    Other Names:
  • Daclatasvir (DCV)

    • 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

    Drug: BMS-650032
    Other Names:
  • Asunaprevir (ASV)

    • Drug: BMS-790052
    Other Names:
  • Daclatasvir (DCV)

    • 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

    Drug: BMS-650032
    Other Names:
  • Asunaprevir (ASV)

    • Drug: BMS-790052
    Other Names:
  • Daclatasvir (DCV)

    • 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

    Drug: BMS-650032
    Other Names:
  • Asunaprevir (ASV)

    • Drug: BMS-790052
    Other Names:
  • Daclatasvir (DCV)

    • 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

    Drug: BMS-650032
    Other Names:
  • Asunaprevir (ASV)

    • Drug: BMS-790052
    Other Names:
  • Daclatasvir (DCV)

    • 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]

    Drug: BMS-650032
    Other Names:
  • Asunaprevir (ASV)

    • Drug: BMS-790052
    Other Names:
  • Daclatasvir (DCV)

    • Drug: BMS-791325

    Drug: Ribavirin
    Other Names:
  • Copegus®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Sustained virologic response (SVR) at 12 weeks post-treatment (SVR12) [12 weeks post-treatment]

    Secondary Outcome Measures

    1. Proportion of subjects with HCV ribonucleic acid (RNA) < limit of quantification (LOQ) (detectable and undetectable) [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]

    2. Proportion of subjects with HCV ribonucleic acid (RNA) undetectable [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]

    3. Proportion of subjects who experience viral breakthrough [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

    4. 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) [End of treatment (Maximum up to 24 Weeks)]

    5. Maximum observed plasma concentration (Cmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [Day 1 and Day 14]

    6. Observed plasma concentration at 12 hours (C12) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [Day 1 and Day 14]

    7. Observed plasma concentration at 24 hours (C24) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [Day 1 and Day 14]

    8. Trough observed plasma concentration (Ctrough) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [Day 1 and Day 14]

    9. Time of maximum observed plasma concentration (Tmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [Day 1 and Day 14]

    10. Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 [Day 1 and Day 14]

    11. HCV genomic substitutions associated with exposure of BMS-650032, BMS-790052, and BMS-791325 [At the time of viral breakthrough or relapse]

    12. 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 [Formal analysis at week 48 of follow up period (or upon occurrence)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The Kirklin Clinic Birmingham Alabama United States 35294
    2 Southern California Research Center Coronado California United States 92118
    3 Peter J Ruane Md Inc Los Angeles California United States 90036
    4 Va Greater Los Angeles Healthcare System Los Angeles California United States 90073
    5 Research And Education, Inc. San Diego California United States 92105
    6 Precision Research Institute, Llc San Diego California United States 92114
    7 Medical Associates Research Group San Diego California United States 92123
    8 University Of Colorado Denver And Hospital Aurora Colorado United States 80045
    9 Medstar Georgetown University Hospital Washington, D.C. District of Columbia United States 20007
    10 Orlando Immunology Center Orlando Florida United States 32803
    11 Miami Research Associates South Miami Florida United States 33143
    12 Atlanta Gastroenterology Associates, Llc Atlanta Georgia United States 30308
    13 Mercy Medical Center, Inc. Baltimore Maryland United States 21202
    14 Johns Hopkins University Lutherville Maryland United States 21093
    15 Id Care Hillsborough New Jersey United States 08844
    16 Southwest Care Center Santa Fe New Mexico United States 87505
    17 James J Peters Vamc The Bronx New York United States 10468
    18 Options Health Research, Llc Tulsa Oklahoma United States 74104
    19 Healthcare Research Consultants Tulsa Oklahoma United States 74135
    20 Texas Clinical Research Institute Arlington Texas United States 76012
    21 Research Specialists Of Texas Houston Texas United States 77030
    22 Alamo Medical Research San Antonio Texas United States 78215
    23 Lifetree Clinical Research Salt Lake City Utah United States 84106
    24 Metropolitan Research Fairfax Virginia United States 22031
    25 Inova Fairfax Hospital Falls Church Virginia United States 22042
    26 Dean Clinic Madison Wisconsin United States 53715
    27 Local Institution Clichy Cedex France 92118
    28 Local Institution Creteil Cedex France 9410
    29 Local Institution Limoges France 87042
    30 Local Institution Marseille Cedex 08 France 13285
    31 Local Institution Paris Cedex 14 France 75679
    32 Fundacion De Investigacion De Diego San Juan Puerto Rico 00927

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT01455090
    Other Study ID Numbers:
    • AI443-014
    • 2011-002788-11
    First Posted:
    Oct 19, 2011
    Last Update Posted:
    Apr 27, 2017
    Last Verified:
    Apr 1, 2017
    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis C
    Hepatitis C, Chronic
    Hepatitis
    Ribavirin
    Asunaprevir

    Study Results

    No Results Posted as of Apr 27, 2017