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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

Phase 2
Completed
Conditions
Chronic Hepatitis C
Interventions
Registration Number
NCT01455090
Lead Sponsor
Bristol-Myers Squibb
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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
320
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group 4:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)BMS-650032\* 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
Group11:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)BMS-650032\* 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
Group 4:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)BMS-790052\* 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
Group 5:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)BMS-650032\* 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
Group 5:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)BMS-791325\* 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
Group 6:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)BMS-650032\* 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
Group 7:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)BMS-650032\* 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
Group 7:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)BMS-791325\* 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
Group 8:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)BMS-650032\* 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
Group 1:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)BMS-650032BMS-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
Group 1:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)BMS-791325BMS-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
Group 9:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)BMS-790052\* 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
Group10:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)BMS-650032\* 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
Group 2:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)BMS-650032BMS-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
Group 2:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)BMS-791325BMS-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
Group12:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)BMS-650032\* 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
Grp13:BMS-650032(200mg)+BMS-790052(30mg)+BMS-791325(75mg)+RBVBMS-650032\* 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 \[if subject is \< 75 kg: 1000 mg per day orally (2 x 200 mg tablets in AM and 3 x 200 mg tablets in PM), or if ≥ 75 kg: 1200 mg per day orally (3 x 200 mg tablets in AM and 3 x 200 mg tablets in PM\]
Group 6:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)BMS-791325\* 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
Group 8:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)BMS-791325\* 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
Group 9:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)BMS-791325\* 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
Group10:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)BMS-791325\* 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
Grp13:BMS-650032(200mg)+BMS-790052(30mg)+BMS-791325(75mg)+RBVBMS-791325\* 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 \[if subject is \< 75 kg: 1000 mg per day orally (2 x 200 mg tablets in AM and 3 x 200 mg tablets in PM), or if ≥ 75 kg: 1200 mg per day orally (3 x 200 mg tablets in AM and 3 x 200 mg tablets in PM\]
Group 3:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)BMS-791325\* 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
Group 4:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)BMS-791325\* 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
Group11:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)BMS-791325\* 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
Group12:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)BMS-791325\* 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
Group 3:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)BMS-650032\* 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
Group 9:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)BMS-650032\* 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
Group 1:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)BMS-790052BMS-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
Group 2:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg)BMS-790052BMS-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
Group 3:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(150mg)BMS-790052\* 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
Group 5:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)BMS-790052\* 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
Group 6:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)BMS-790052\* 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
Group 7:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)BMS-790052\* 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
Group 8:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)BMS-790052\* 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
Group10:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)BMS-790052\* 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
Group11:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(75mg)BMS-790052\* 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
Group12:BMS-650032(200 mg)+BMS-790052(30 mg)+BMS-791325(150mg)BMS-790052\* 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
Grp13:BMS-650032(200mg)+BMS-790052(30mg)+BMS-791325(75mg)+RBVBMS-790052\* 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 \[if subject is \< 75 kg: 1000 mg per day orally (2 x 200 mg tablets in AM and 3 x 200 mg tablets in PM), or if ≥ 75 kg: 1200 mg per day orally (3 x 200 mg tablets in AM and 3 x 200 mg tablets in PM\]
Grp13:BMS-650032(200mg)+BMS-790052(30mg)+BMS-791325(75mg)+RBVRibavirin\* 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 \[if subject is \< 75 kg: 1000 mg per day orally (2 x 200 mg tablets in AM and 3 x 200 mg tablets in PM), or if ≥ 75 kg: 1200 mg per day orally (3 x 200 mg tablets in AM and 3 x 200 mg tablets in PM\]
Primary Outcome Measures
NameTimeMethod
Sustained virologic response (SVR) at 12 weeks post-treatment (SVR12)12 weeks post-treatment
Secondary Outcome Measures
NameTimeMethod
Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-650032, BMS-790052, BMS 791325, and BMS-794712Day 1 and Day 14
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
Proportion of subjects with HCV ribonucleic acid (RNA) undetectableWeeks 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 breakthroughFormal 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)End of treatment (Maximum up to 24 Weeks)
Maximum observed plasma concentration (Cmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712Day 1 and Day 14
Observed plasma concentration at 12 hours (C12) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712Day 1 and Day 14
Observed plasma concentration at 24 hours (C24) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712Day 1 and Day 14
Trough observed plasma concentration (Ctrough) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712Day 1 and Day 14
Time of maximum observed plasma concentration (Tmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712Day 1 and Day 14
HCV genomic substitutions associated with exposure of BMS-650032, BMS-790052, and BMS-791325At 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 abnormalitiesFormal analysis at week 48 of follow up period (or upon occurrence)

Trial Locations

Locations (28)

The Kirklin Clinic

🇺🇸

Birmingham, Alabama, United States

Southern California Research Center

🇺🇸

Coronado, California, United States

Peter J Ruane Md Inc

🇺🇸

Los Angeles, California, United States

Va Greater Los Angeles Healthcare System

🇺🇸

Los Angeles, California, United States

Research And Education, Inc.

🇺🇸

San Diego, California, United States

Precision Research Institute, Llc

🇺🇸

San Diego, California, United States

Medical Associates Research Group

🇺🇸

San Diego, California, United States

University Of Colorado Denver And Hospital

🇺🇸

Aurora, Colorado, United States

Medstar Georgetown University Hospital

🇺🇸

Washington, D.C., District of Columbia, United States

Orlando Immunology Center

🇺🇸

Orlando, Florida, United States

Scroll for more (18 remaining)
The Kirklin Clinic
🇺🇸Birmingham, Alabama, United States

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