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Study to Determine the Safety and Effectiveness of Antiviral Combination Therapy to Treat Hepatitis C Virus (HCV) Infected Patients Who Have Previously Not Been Treated With Standard of Care

This study has been completed.
Sponsor:
Collaborator:
Pharmasset
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01359644
First received: May 23, 2011
Last updated: December 4, 2013
Last verified: December 2013
  Purpose

The purpose of the study is to determine whether therapy with the combination of PSI-7977 and BMS-790052 with or without Ribavirin is effective in treating Hepatitis C infection when given for 12 or 24 weeks as measured by sustained virologic response (SVR) with undetectable HCV RNA 12 weeks post treatment


Condition Intervention Phase
Chronic Hepatitis C
Drug: PSI-7977
Drug: BMS-790052
Drug: Ribavirin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Parallel, Open-Label, Randomized Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of PSI-7977 in Combination With BMS-790052 With or Without Ribavirin in Treatment Naive Subjects Chronically Infected With Hepatitis C Virus Genotypes 1, 2, or 3

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Sustained Virologic Response (SVR) at post treatment week 24 defined by undetectable HCV RNA at 24 weeks post treatment. [ Time Frame: 24 weeks post treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Frequency of deaths, SAEs, discontinuations due to AEs, and severity Grade 3/4 laboratory abnormalities. [ Time Frame: 24 Weeks post-treatment ] [ Designated as safety issue: Yes ]
  • Maximum observed plasma concentration (Cmax) [ Time Frame: Day 7 and Day 14 ] [ Designated as safety issue: No ]
    Pharmacokinetics of BMS-790052, PSI-7977, and PSI-6206 will be derived from plasma concentration versus time data on Days 7 (PSI-7977 and PSI-6206 for subjects in treatment groups A and B only) and 14.

  • Trough observed concentration (Cmin) [ Time Frame: Day 7 and Day 14 ] [ Designated as safety issue: No ]
    Pharmacokinetics of BMS-790052, PSI-7977, and PSI-6206 will be derived from plasma concentration versus time data on Days 7 (PSI-7977 and PSI-6206 for subjects in treatment groups A and B only) and 14.

  • Time of maximum observed concentration (Tmax) [ Time Frame: Day 7 and Day 14 ] [ Designated as safety issue: No ]
    Pharmacokinetics of BMS-790052, PSI-7977, and PSI-6206 will be derived from plasma concentration versus time data on Days 7 (PSI-7977 and PSI-6206 for subjects in treatment groups A and B only) and 14.

  • Area under the concentration-time curve in one dosing interval [AUC(TAU)] [ Time Frame: Day 7 and Day 14 ] [ Designated as safety issue: No ]
    Pharmacokinetics of BMS-790052, PSI-7977, and PSI-6206 will be derived from plasma concentration versus time data on Days 7 (PSI-7977 and PSI-6206 for subjects in treatment groups A and B only) and 14.

  • Proportions of subjects who experience: rapid virologic response (RVR)[i.e, undetectable HCV ribonucleic acid (RNA) following 4 weeks of treatment] [ Time Frame: Screening, Days -1 (baseline), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 9, Day 11, Day 14, Day 21, every 2 weeks from week 4 until end of treatment and at the Post-treatment 4 weeks, 12 weeks , 24 weeks, 36 weeks, 48 weeks ] [ Designated as safety issue: No ]
  • Proportions of subjects who experience: extended rapid virologic response (eRVR)[i.e., undetectable HCV RNA following 4 and 12 weeks of treatment]. [ Time Frame: Screening, Days -1 (baseline), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 9, Day 11, Day 14, Day 21, every 2 weeks from week 4 until end of treatment and at the Post-treatment 4 weeks, 12 weeks , 24 weeks, 36 weeks, 48 weeks ] [ Designated as safety issue: No ]
  • Proportions of subjects who experience: complete early virologic response (cEVR) [i.e., undetectable HCV RNA following 12 weeks of treatment] [ Time Frame: Screening, Days -1 (baseline), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 9, Day 11, Day 14, Day 21, every 2 weeks from week 4 until end of treatment and at the Post-treatment 4 weeks, 12 weeks , 24 weeks, 36 weeks, 48 weeks ] [ Designated as safety issue: No ]
  • Proportions of subjects who experience: undetectable HCV RNA at end of treatment [ Time Frame: Screening, Days -1 (baseline), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 9, Day 11, Day 14, Day 21, every 2 weeks from week 4 until end of treatment and at the Post-treatment 4 weeks, 12 weeks , 24 weeks, 36 weeks, 48 weeks ] [ Designated as safety issue: No ]
  • Proportions of subjects who experience: sustained virologic response at post treatment week 12 (SVR12) [i.e., undetectable HCV RNA at 12 weeks post treatment] [ Time Frame: Screening, Days -1 (baseline), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 9, Day 11, Day 14, Day 21, every 2 weeks from week 4 until end of treatment and at the Post-treatment 4 weeks, 12 weeks , 24 weeks, 36 weeks, 48 weeks ] [ Designated as safety issue: No ]
  • Proportions of subjects who experience: Virologic breakthrough or relapse [ Time Frame: Screening, Days -1 (baseline), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 9, Day 11, Day 14, Day 21, every 2 weeks from week 4 until end of treatment and at the Post-treatment 4 weeks, 12 weeks , 24 weeks, 36 weeks, 48 weeks ] [ Designated as safety issue: No ]
  • Characterization of HCV genomic substitutions associated with exposure of BMS-790052 and PSI-7977 [ Time Frame: Screening, Days -1 (baseline), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 9, Day 11, Day 14, Day 21, every 2 weeks from week 4 until end of treatment and at the Post-treatment 4 weeks, 12 weeks , 24 weeks, 36 weeks, 48 weeks ] [ Designated as safety issue: No ]

Enrollment: 208
Study Start Date: June 2011
Study Completion Date: October 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A: PSI-7977 + BMS-790052

PSI-7977 Once daily for 7 days then add once daily BMS-790052

Genotype 1a or 1b

Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 24 weeks
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 24 weeks
Experimental: Treatment B: PSI-7977 + BMS-790052

PSI-7977 Once daily for 7 days then add once daily BMS-790052.

Genotype 2 or 3

Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 24 weeks
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 24 weeks
Experimental: Treatment C: PSI-7977 + BMS-790052
Genotype 1a or 1b
Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 24 weeks
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 24 weeks
Experimental: Treatment D: PSI-7977 + BMS-790052
Genotype 2 or 3
Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 24 weeks
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 24 weeks
Experimental: Treatment E: PSI-7977 + BMS-790052 + Ribavirin
Genotype 1a or 1b
Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 24 weeks
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 24 weeks
Drug: Ribavirin
Tablets, Oral, 200mg, For subjects weighing < 75 kg:1000 mg; for subjects weighing ≥ 75: 1200 mg, Twice daily < 75 kg: 400 mg in AM and 600 mg in PM; ≥ 75: 600 mg in AM and PM, 24 weeks
Other Name: Copegus ®
Experimental: Treatment F: PSI-7977 + BMS-790052 + Ribavirin
Genotype 2 or 3
Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 24 weeks
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 24 weeks
Drug: Ribavirin
Tablets, Oral, 200mg, 400 mg (2 tablets) in AM and 400 mg (2 tablets) in PM, 24 weeks
Other Name: Copegus ®
Experimental: Treatment G: PSI-7977 + BMS-790052

HCV GT1 treatment naive subjects

Genotype 1a or 1b

Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 12 weeks
Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 12 weeks
Experimental: Treatment H: PSI-7977 + BMS-790052 + Ribavirin

HCV GT1 treatment naive subjects

Genotype 1a or 1b

Drug: Ribavirin
Tablets, Oral, 200mg, For subjects weighing < 75 kg:1000 mg; for subjects weighing ≥ 75: 1200 mg, Twice daily < 75 kg: 400 mg in AM and 600 mg in PM; ≥ 75: 600 mg in AM and PM, 12 weeks
Other Name: Copegus ®
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 12 weeks
Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 12 weeks
Experimental: Treatment I: PSI-7977 + BMS-790052

Subjects who experienced Telaprevir (TVR)/Boceprevir (BOC) treatment failure

Genotype 1a or 1b

Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 24 weeks
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 24 weeks
Experimental: Treatment J: PSI-7977 + BMS-790052 + Ribavirin

Subjects who experienced TVR/BOC Treatment failure

Genotype 1a or 1b

Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 24 weeks
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 24 weeks
Drug: Ribavirin
Tablets, Oral, 200mg, For subjects weighing < 75 kg:1000 mg; for subjects weighing ≥ 75: 1200 mg, Twice daily < 75 kg: 400 mg in AM and 600 mg in PM; ≥ 75: 600 mg in AM and PM, 24 weeks
Other Name: Copegus ®

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects ages 18 to 70 years.
  • HCV-Infected Genotype 1, 2 or 3 subjects who have no previous exposure to an interferon formulation [ie interferon-alfa (IFNα), pegylated interferon-alfa (pegIFNα)], Ribavirin (RBV); or other HCV-specific direct acting antiviral (including BMS-790052 and PSI-7977).
  • Subjects should have chronic hepatitis C (CHC) genotype 1a, 1b, 2, or 3 as documented by: i) 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.

Exclusion Criteria:

  • Evidence of a medical condition associate with chronic liver disease other than HCV.
  • History of variceal bleeding, hepatic encephalopathy, or ascites requiring management with diuretics or paracentesis.
  • History of hemophilia.
  • History of Torsade de pointes.
  • 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.
  • History of gastrointestinal disease or surgical procedure (except Cholecystectomy).
  • History of clinically significant cardiac disease.
  • Blood transfusion within 4 weeks prior to study drug administration.
  • Poor venous access.
  • Any other medical, psychiatric and/or social reason which, in the opinion of the Investigator, would make the candidate inappropriate for participation in this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01359644

Locations
United States, California
Southern California Liver Centers
Coronado, California, United States, 92118
Research And Education, Inc.
San Diego, California, United States, 92105
United States, Colorado
University Of Colorado Denver & Hospital
Aurora, Colorado, United States, 80045
United States, Florida
University Of Florida Hepatology
Gainesville, Florida, United States, 32610
Orlando Immunology Center
Orlando, Florida, United States, 32803
Miami Research Associates
South Miami, Florida, United States, 33143
United States, Maryland
Mercy Medical Center
Baltimore, Maryland, United States, 21202
Johns Hopkins University
Lutherville, Maryland, United States, 21093
United States, Michigan
University Of Michigan Health System
Ann Arbor, Michigan, United States, 48109
United States, New York
Bronx Va Medical Center 3c Sub-J
Bronx, New York, United States, 10468
Weill Cornell Medical College
New York, New York, United States, 10021
United States, Oklahoma
Healthcare Research Consultants
Tulsa, Oklahoma, United States, 74135
Options Health Research, Llc
Tulsa, Oklahoma, United States, 74104
United States, Pennsylvania
University Of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Alamo Medical Research
San Antonio, Texas, United States, 78215
United States, Virginia
Metropolitan Research
Annandale, Virginia, United States, 22003
United States, Wisconsin
Dean Clinic
Madison, Wisconsin, United States, 53715
Puerto Rico
Local Institution
San Juan, Puerto Rico, 00927
Sponsors and Collaborators
Bristol-Myers Squibb
Pharmasset
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01359644     History of Changes
Other Study ID Numbers: AI444-040
Study First Received: May 23, 2011
Last Updated: December 4, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014