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

Phase 2
Completed
Conditions
Chronic Hepatitis C
Interventions
Registration Number
NCT01359644
Lead Sponsor
Bristol-Myers Squibb
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
350
Inclusion Criteria
  • Men and women, ages 18 to 70 years.
  • Participants infected with hepatitis C virus (HCV) genotype 1, 2, or 3, with no previous exposure to an interferon formulation (ie, interferon-alpha, pegylated interferon-alpha) ribavirin, or other HCV-specific direct-acting antiviral (including daclatasvir and PSI-7977).
  • Patients should have chronic hepatitis C genotype 1a, 1b, 2, or 3 as documented by: positive test results for anti-HCV antibody; HCV RNA; or a HCV genotype at least 6 months prior to screening, and 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Treatment A: PSI-7977 + DaclatasvirPSI-7977Genotype 1a or 1b
Treatment B: PSI-7977 + DaclatasvirPSI-7977Genotype 2 or 3
Treatment C: PSI-7977 + DaclatasvirPSI-7977Genotype 1a or 1b
Treatment D: PSI-7977 + DaclatasvirPSI-7977Genotype 2 or 3
Treatment H: PSI-7977 + BMS-790052 + RibavirinPSI-7977Hepatitis C virus genotype 1, treatment-naive patients Genotype 1a or 1b
Treatment E: PSI-7977 + Daclatasvir + RibavirinPSI-7977Genotype 1a or 1b
Treatment F: PSI-7977 + Daclatasvir+ RibavirinPSI-7977Genotype 2 or 3
Treatment G: PSI-7977 + DaclatasvirPSI-7977Hepatitis C virus genotype 1, treatment-naive patients Genotype 1a or 1b
Treatment I: PSI-7977 + DaclatasvirPSI-7977Patients who experienced telaprevir/boceprevir treatment failure Genotype 1a or 1b
Treatment I: PSI-7977 + DaclatasvirDaclatasvirPatients who experienced telaprevir/boceprevir treatment failure Genotype 1a or 1b
Treatment J: PSI-7977 + Daclatasvir + RibavirinPSI-7977Patients who experienced telaprevir/boceprevir treatment failure Genotype 1a or 1b
Treatment B: PSI-7977 + DaclatasvirDaclatasvirGenotype 2 or 3
Treatment A: PSI-7977 + DaclatasvirDaclatasvirGenotype 1a or 1b
Treatment E: PSI-7977 + Daclatasvir + RibavirinRibavirinGenotype 1a or 1b
Treatment C: PSI-7977 + DaclatasvirDaclatasvirGenotype 1a or 1b
Treatment D: PSI-7977 + DaclatasvirDaclatasvirGenotype 2 or 3
Treatment H: PSI-7977 + BMS-790052 + RibavirinRibavirinHepatitis C virus genotype 1, treatment-naive patients Genotype 1a or 1b
Treatment E: PSI-7977 + Daclatasvir + RibavirinDaclatasvirGenotype 1a or 1b
Treatment G: PSI-7977 + DaclatasvirDaclatasvirHepatitis C virus genotype 1, treatment-naive patients Genotype 1a or 1b
Treatment F: PSI-7977 + Daclatasvir+ RibavirinDaclatasvirGenotype 2 or 3
Treatment F: PSI-7977 + Daclatasvir+ RibavirinRibavirinGenotype 2 or 3
Treatment H: PSI-7977 + BMS-790052 + RibavirinDaclatasvirHepatitis C virus genotype 1, treatment-naive patients Genotype 1a or 1b
Treatment J: PSI-7977 + Daclatasvir + RibavirinDaclatasvirPatients who experienced telaprevir/boceprevir treatment failure Genotype 1a or 1b
Treatment J: PSI-7977 + Daclatasvir + RibavirinRibavirinPatients who experienced telaprevir/boceprevir treatment failure Genotype 1a or 1b
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Sustained Virologic Response at Post Treatment Week 12 (SVR12)Follow-up Week 12

SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target detected or target not detected (ie, HCV RNA \<25 IU/mL) at follow-up Week 12. DCV=daclatasvir, SOF=sofosbuvir.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24)Follow-up Week 24

SVR24 was defined as participant's hepatitis C virus RNA less than the lower limit of quantitation, target detected or target not detected at follow-up Week 24. DCV=daclatasvir, SOF=sofosbuvir.

Number of Participants Who Died and With Serious Adverse Events (SAEs), Grade 3-4 Adverse Events (AEs), and Grade 3-4 Abnormalities on Laboratory Test Results During Follow-up PeriodAEs: From Day 1 of follow-up period (Week 13 or 25) up to study discharge (up to 72 weeks). SAEs: From Day 1 of follow-up period (Week 13 or 25) up to 30 days after study discharge (up to 74 weeks)

AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Based on the severity, AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Very severe

Percentage of Participants With Viral Breakthrough During the Treatment PeriodFirst dose of study drug (Day 1) up to end of treatment period (up to 12 or 24 weeks, depending on treatment group)

Viral breakthrough is defined as any confirmed increase in viral load ≥1 log from nadir or any confirmed hepatitis C virus RNA levels ≥25 IU/mL on or after Week 8.

Percentage of Participants Who Experienced Viral Relapse During Follow-up PeriodDay 1 of follow-up period (Week 13 or 25, depending on treatment group) to end of follow-up period (up to 48 weeks)

Viral relapse during follow-up is defined as any confirmed quantifiable hepatitis C virus (HCV) RNA ≥25 IU/mL with HCV RNA levels less than the lower limit of quantitation, target detected or target not detected, ie, HCV RNA \<25 IU/mL at the end of treatment.

Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24Baseline, Follow-up week 24

Change from baseline in log10 HCV RNA at scheduled sampling time.

Number of Participants Who Died and With Serious Adverse Events (SAEs) and Grade 3-4 Adverse Events (AEs), During the Treatment Period Prior to Addition of Rescue TherapyFirst dose of study drug (Day 1) up to the start of rescue therapy (12 or 24 weeks, depending on treatment group)

AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Based on the severity, AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Very severe.

Trial Locations

Locations (18)

Mercy Medical Center

🇺🇸

Baltimore, Maryland, United States

Research And Education, Inc.

🇺🇸

San Diego, California, United States

University Of Florida Hepatology

🇺🇸

Gainesville, Florida, United States

University Of Colorado Denver & Hospital

🇺🇸

Aurora, Colorado, United States

University Of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Dean Clinic

🇺🇸

Madison, Wisconsin, United States

Weill Cornell Medical College

🇺🇸

New York, New York, United States

University Of Michigan Health System

🇺🇸

Ann Arbor, Michigan, United States

Local Institution

🇵🇷

San Juan, Puerto Rico

Southern California Liver Centers

🇺🇸

Coronado, California, United States

Orlando Immunology Center

🇺🇸

Orlando, Florida, United States

Alamo Medical Research

🇺🇸

San Antonio, Texas, United States

Johns Hopkins University

🇺🇸

Lutherville, Maryland, United States

Bronx Va Medical Center 3c Sub-J

🇺🇸

Bronx, New York, United States

Miami Research Associates

🇺🇸

South Miami, Florida, United States

Options Health Research, Llc

🇺🇸

Tulsa, Oklahoma, United States

Healthcare Research Consultants

🇺🇸

Tulsa, Oklahoma, United States

Metropolitan Research

🇺🇸

Annandale, Virginia, United States

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