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

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

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

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: PSI-7977; Drug: Daclatasvir; Drug: Ribavirin

• Study Type: Interventional
• Enrollment (Actual): 350
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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 Names: 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 Names: 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 Names: 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 Names: BMS-790052; Drug: Ribavirin; Tablets, oral, 200 mg; Other Names: 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 Names: BMS-790052; Drug: Ribavirin; Tablets, oral, 200 mg; Other Names: 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 Names: 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 Names: BMS-790052; Drug: Ribavirin; Tablets, oral, 200 mg; Other Names: 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 Names: 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 Names: BMS-790052; Drug: Ribavirin; Tablets, oral, 200 mg; Other Names: Copegus ®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained Virologic Response at Post Treatment Week 12 (SVR12)	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.	Follow-up Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24)	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.	Follow-up Week 24
Percentage of Participants With Viral Breakthrough During the Treatment Period	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.	First dose of study drug (Day 1) up to end of treatment period (up to 12 or 24 weeks, depending on treatment group)
Percentage of Participants Who Experienced Viral Relapse During Follow-up Period	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.	Day 1 of follow-up period (Week 13 or 25, depending on treatment group) to end of follow-up period (up to 48 weeks)
Change From Baseline in log10 Hepatitis C Virus (HCV) RNA at Follow-up Week 24	Change from baseline in log10 HCV RNA at scheduled sampling time.	Baseline, Follow-up week 24
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	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.	First dose of study drug (Day 1) up to the start of rescue therapy (12 or 24 weeks, depending on treatment group)
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	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	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)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Pharmasset

Publications and helpful links

General Publications

• Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson I, Lawitz E, Lok AS, Hinestrosa F, Thuluvath PJ, Schwartz H, Nelson DR, Everson GT, Eley T, Wind-Rotolo M, Huang SP, Gao M, Hernandez D, McPhee F, Sherman D, Hindes R, Symonds W, Pasquinelli C, Grasela DM; AI444040 Study Group. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014 Jan 16;370(3):211-21. doi: 10.1056/NEJMoa1306218. Erratum In: N Engl J Med. 2014 Apr 10;370(15):1469.

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: May 23, 2011
• First Submitted That Met QC Criteria: May 24, 2011
• First Posted (Estimate): May 25, 2011

Study Record Updates

• Last Update Posted (Estimate): October 23, 2015
• Last Update Submitted That Met QC Criteria: September 23, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Sofosbuvir; Ribavirin
• Other Study ID Numbers: AI444-040