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:
- 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
- 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:
- Documented Fibrotest score of ≤0.72 and aspartate transferase (transminase) to platelet ratio index (APRI) ≤2; OR
- Documented liver biopsy within 36 months preceding Day 1 showing absence of cirrhosis OR
- 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
Group Intervention Description 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-650032 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 Group 1:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg) BMS-791325 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 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-650032 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 Group 2:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg) BMS-791325 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 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)+RBV BMS-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)+RBV BMS-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-790052 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 Group 2:BMS-650032(200 mg)+BMS-790052(60 mg)+BMS-791325(75mg) BMS-790052 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 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)+RBV BMS-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)+RBV Ribavirin \* 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
Name Time Method Sustained virologic response (SVR) at 12 weeks post-treatment (SVR12) 12 weeks post-treatment
- Secondary Outcome Measures
Name Time Method 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) 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 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 8Proportion 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-794712 Day 1 and Day 14 Observed plasma concentration at 12 hours (C12) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 Day 1 and Day 14 Observed plasma concentration at 24 hours (C24) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 Day 1 and Day 14 Trough observed plasma concentration (Ctrough) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 Day 1 and Day 14 Time of maximum observed plasma concentration (Tmax) of BMS-650032, BMS-790052, BMS 791325, and BMS-794712 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 Day 1 and Day 14 HCV genomic substitutions associated with exposure of BMS-650032, BMS-790052, and BMS-791325 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 Formal analysis at week 48 of follow up period (or upon occurrence)
Trial Locations
- Locations (28)
Fundacion De Investigacion De Diego
🇵🇷San Juan, Puerto Rico
James J Peters Vamc
🇺🇸The Bronx, New York, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Id Care
🇺🇸Hillsborough, New Jersey, United States
Southwest Care Center
🇺🇸Santa Fe, New Mexico, United States
Local Institution
🇫🇷Paris Cedex 14, France
Healthcare Research Consultants
🇺🇸Tulsa, Oklahoma, United States
Miami Research Associates
🇺🇸South Miami, Florida, United States
Medstar Georgetown University Hospital
🇺🇸Washington, D.C., District of Columbia, United States
Southern California Research Center
🇺🇸Coronado, California, United States
Options Health Research, Llc
🇺🇸Tulsa, Oklahoma, United States
Texas Clinical Research Institute
🇺🇸Arlington, Texas, United States
Metropolitan Research
🇺🇸Fairfax, Virginia, 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
Mercy Medical Center, Inc.
🇺🇸Baltimore, Maryland, United States
Research Specialists Of Texas
🇺🇸Houston, Texas, United States
Alamo Medical Research
🇺🇸San Antonio, Texas, United States
Atlanta Gastroenterology Associates, Llc
🇺🇸Atlanta, Georgia, United States
Johns Hopkins University
🇺🇸Lutherville, Maryland, United States
Dean Clinic
🇺🇸Madison, Wisconsin, United States
The Kirklin Clinic
🇺🇸Birmingham, Alabama, United States
University Of Colorado Denver And Hospital
🇺🇸Aurora, Colorado, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
Lifetree Clinical Research
🇺🇸Salt Lake City, Utah, United States