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

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: September 23, 2015
Last verified: September 2015
  Purpose
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

Condition Intervention Phase
Chronic Hepatitis C
Drug: PSI-7977
Drug: Daclatasvir
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:
  • Percentage of Participants With Sustained Virologic Response at Post Treatment Week 12 (SVR12) [ Time Frame: Follow-up Week 12 ] [ Designated as safety issue: No ]
    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:
  • Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24) [ Time Frame: Follow-up Week 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Viral Breakthrough During the Treatment Period [ Time Frame: First dose of study drug (Day 1) up to end of treatment period (up to 12 or 24 weeks, depending on treatment group) ] [ Designated as safety issue: No ]
    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 Period [ Time Frame: Day 1 of follow-up period (Week 13 or 25, depending on treatment group) to end of follow-up period (up to 48 weeks) ] [ Designated as safety issue: No ]
    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 24 [ Time Frame: Baseline, Follow-up week 24 ] [ Designated as safety issue: No ]
    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 Therapy [ Time Frame: First dose of study drug (Day 1) up to the start of rescue therapy (12 or 24 weeks, depending on treatment group) ] [ Designated as safety issue: Yes ]
    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.

  • 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 Period [ Time Frame: AEs: 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) ] [ Designated as safety issue: Yes ]
    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


Enrollment: 350
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 + Daclatasvir
Genotype 1a or 1b
Drug: PSI-7977
Tablets, oral, 400 mg, once daily
Drug: Daclatasvir
Tablets, oral, 60 mg, once daily
Other Name: BMS-790052
Experimental: Treatment B: PSI-7977 + Daclatasvir
Genotype 2 or 3
Drug: PSI-7977
Tablets, oral, 400 mg, once daily
Drug: Daclatasvir
Tablets, oral, 60 mg, once daily
Other Name: BMS-790052
Experimental: Treatment C: PSI-7977 + Daclatasvir
Genotype 1a or 1b
Drug: PSI-7977
Tablets, oral, 400 mg, once daily
Drug: Daclatasvir
Tablets, oral, 60 mg, once daily
Other Name: BMS-790052
Experimental: Treatment D: PSI-7977 + Daclatasvir
Genotype 2 or 3
Drug: PSI-7977
Tablets, oral, 400 mg, once daily
Drug: Daclatasvir
Tablets, oral, 60 mg, once daily
Other Name: BMS-790052
Experimental: Treatment E: PSI-7977 + Daclatasvir + Ribavirin
Genotype 1a or 1b
Drug: PSI-7977
Tablets, oral, 400 mg, once daily
Drug: Daclatasvir
Tablets, oral, 60 mg, once daily
Other Name: BMS-790052
Drug: Ribavirin
Tablets, oral, 200 mg
Other Name: Copegus ®
Experimental: Treatment F: PSI-7977 + Daclatasvir+ Ribavirin
Genotype 2 or 3
Drug: PSI-7977
Tablets, oral, 400 mg, once daily
Drug: Daclatasvir
Tablets, oral, 60 mg, once daily
Other Name: BMS-790052
Drug: Ribavirin
Tablets, oral, 200 mg
Other Name: Copegus ®
Experimental: Treatment G: PSI-7977 + Daclatasvir

Hepatitis C virus genotype 1, treatment-naive patients

Genotype 1a or 1b

Drug: PSI-7977
Tablets, oral, 400 mg, once daily
Drug: Daclatasvir
Tablets, oral, 60 mg, once daily
Other Name: BMS-790052
Experimental: Treatment H: PSI-7977 + BMS-790052 + Ribavirin

Hepatitis C virus genotype 1, treatment-naive patients

Genotype 1a or 1b

Drug: PSI-7977
Tablets, oral, 400 mg, once daily
Drug: Daclatasvir
Tablets, oral, 60 mg, once daily
Other Name: BMS-790052
Drug: Ribavirin
Tablets, oral, 200 mg
Other Name: Copegus ®
Experimental: Treatment I: PSI-7977 + Daclatasvir

Patients who experienced telaprevir/boceprevir treatment failure

Genotype 1a or 1b

Drug: PSI-7977
Tablets, oral, 400 mg, once daily
Drug: Daclatasvir
Tablets, oral, 60 mg, once daily
Other Name: BMS-790052
Experimental: Treatment J: PSI-7977 + Daclatasvir + Ribavirin

Patients who experienced telaprevir/boceprevir treatment failure

Genotype 1a or 1b

Drug: PSI-7977
Tablets, oral, 400 mg, once daily
Drug: Daclatasvir
Tablets, oral, 60 mg, once daily
Other Name: BMS-790052
Drug: Ribavirin
Tablets, oral, 200 mg
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:

  • 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.
  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
Options Health Research, Llc
Tulsa, Oklahoma, United States, 74104
Healthcare Research Consultants
Tulsa, Oklahoma, United States, 74135
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:
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
Results First Received: August 21, 2015
Last Updated: September 23, 2015
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 May 03, 2016