Study of Daclatasvir (BMS-790052) Add-on to Standard of Care in Treatment- naïve Patients (HEPCAT)

A Phase 2b Study of Daclatasvir in Combination With Peg-Interferon Alfa-2a and Ribavirin in Treatment Naive Subjects With Chronic Hepatitis C Genotype 1 and 4 Infection

To establish that at least 1 dose of daclatasvir combined with standard of care (pegylated interferon and ribavirin) is safe and well tolerated and demonstrates extended rapid virologic response rates at least 35% greater than those with placebo.

Study Overview

• Status: Completed
• Conditions: Hepatitis C Virus
• Intervention / Treatment: Drug: Daclatasvir; Drug: Daclatasvir; Drug: peg-interferon alfa-2a; Drug: ribavirin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 558
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia, NSW 2050
    • Local Institution
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Local Institution
    • Westmead Nsw, New South Wales, Australia, 2145
      • Local Institution
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Local Institution
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Local Institution
  • Victoria
    • Clayton Vic, Victoria, Australia, 3168
      • Local Institution
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Local Institution
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • Local Institution
    • Victoria, British Columbia, Canada, V8V 3P9
      • Local Institution
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • Local Institution
    • Toronto, Ontario, Canada, M5T 2S8
      • Local Institution
• Denmark
  • Aarhus, Denmark, 8200
    • Local Institution
  • Hvidovre, Denmark, 2650
    • Local Institution
  • Odense, Denmark, 5000
    • Local Institution
• Egypt
  • Cairo, Egypt, 11559
    • Local Institution
  • Menoufiya
    • Shebin Elkom, Menoufiya, Egypt, 35111
      • Local Institution
• France
  • Creteil, France, 94000
    • Local Institution
  • Marseille Cedex 08, France, 13285
    • Local Institution
  • Montpellier Cedex 5, France, 34295
    • Local Institution
  • Paris Cedex 12, France, 75571
    • Local Instituition
  • Paris Cedex 14, France, 75679
    • Local Institution
• Germany
  • Duesseldorf, Germany, 40237
    • Local Institution
  • Essen, Germany, 45122
    • Local Institution
  • Frankfurt, Germany, 60590
    • Local Institution
  • Hamburg, Germany, 20099
    • Local Institution
• Italy
  • Cisanello (pisa), Italy, 56124
    • Local Institution
  • Pavia, Italy, 27100
    • Local Institution
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44340
      • Local Institution
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Local Institution
• Sweden
  • Gothenburg, Sweden, SE-416 85
    • Local Institution
  • Stockholm, Sweden, 141 86
    • Local Institution
• United States
  • Alabama
    • Montgomery, Alabama, United States, 36116
      • Alabama Liver & Digestive Specialists (Alds)
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic
    • Los Angeles, California, United States, 90048
      • CLI
    • San Diego, California, United States, 92114
      • Desta Digestive Disease Medical Center
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
    • San Francisco, California, United States, 94118
      • Kaiser Permanente Medical Center
    • San Francisco, California, United States, 94110
      • University Of California, San Francisco/Sf General Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Transplant Center And Hepatology Clinic, B-154
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
  • Florida
    • Gainesville, Florida, United States, 32610
      • University Of Florida Hepatology
    • Miami, Florida, United States, 33136
      • University of Miami
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
    • Baltimore, Maryland, United States, 21229
      • Digestive Disease Associates, P.A.
    • Lutherville, Maryland, United States, 21093
      • Johns Hopkins University
  • Massachusetts
    • Springfield, Massachusetts, United States, 01105
      • Claudia T. Martorell, Md, Llc
  • New York
    • Bronx, New York, United States, 10468
      • James J Peters VAMC
    • Great Neck, New York, United States, 11201
      • James Sungsik Park, M.D. C.N.S.C.
    • Monticello, New York, United States, 12701
      • Upper Delaware Valley Infectious Diseases, Pc
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University Of North Carolina At Chapel Hill School Of Med
    • Statesville, North Carolina, United States, 28677
      • Carolinas Center For Liver Disease
  • 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
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • University Gastroenterology
  • Tennessee
    • Nashville, Tennessee, United States, 37205
      • Nashville Medical Research Institute
  • Texas
    • Arlington, Texas, United States, 76012
      • North Texas Research Institute
    • Houston, Texas, United States, 77030
      • St. Luke'S Episcopal Hospital - Baylor College Of Medicine
    • San Antonio, Texas, United States, 78215
      • Alamo Medical Research
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • 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:

• Patients chronically infected with hepatitis C virus (HCV) genotype 1 or 4
• HCV RNA viral load of ≥100,000 IU/mL
• No previous exposure to interferon, pegIFNα, or RBV
• Results of a liver biopsy demonstrating absence of cirrhosis obtained ≤24 months prior to randomization. Compensated cirrhotics with Hepatitis C virus genotype 1 infection are eligible, but will be capped at 10% of the randomized study population (biopsy can be from any time period prior to randomization)
• Findings on ultrasound, computed tomography scan, or magnetic resonance imaging 12 months prior to randomization that do not demonstrate evidence of hepatocellular carcinoma
• Body mass index of 18 to 35 kg/m^2

Exclusion Criteria:

• Positive for hepatitis B or HIV-1/HIV-2 antibody at screening
• Evidence of a medical condition associated with chronic liver disease other than HCV
• Evidence of decompensated cirrhosis based on radiologic criteria or biopsy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Daclatasvir plus peg-interferon alfa-2a and ribavirin (20 mg)	Drug: Daclatasvir; Tablets, oral, 20 mg, once daily, 12-24 weeks, depending on response; Drug: Daclatasvir; Tablets, oral, 60 mg, once daily, 12-24 weeks, depending on response; Drug: peg-interferon alfa-2a; Syringe, subcutaneous Injection, 180 µg, once weekly, 24 or 48 weeks depending on response; Other Names: Pegasys; Drug: ribavirin; Tablets, oral, 1000 or 1200 mg based on weight, once daily, 24 or 48 weeks depending on response; Other Names: Copegus
Experimental: Daclatasvir plus peg-interferon alfa-2a and ribavirin (60 mg)	Drug: Daclatasvir; Tablets, oral, 20 mg, once daily, 12-24 weeks, depending on response; Drug: Daclatasvir; Tablets, oral, 60 mg, once daily, 12-24 weeks, depending on response; Drug: peg-interferon alfa-2a; Syringe, subcutaneous Injection, 180 µg, once weekly, 24 or 48 weeks depending on response; Other Names: Pegasys; Drug: ribavirin; Tablets, oral, 1000 or 1200 mg based on weight, once daily, 24 or 48 weeks depending on response; Other Names: Copegus
Placebo Comparator: Placebo plus peg-interferon alfa-2a and ribavirin	Drug: peg-interferon alfa-2a; Syringe, subcutaneous Injection, 180 µg, once weekly, 24 or 48 weeks depending on response; Other Names: Pegasys; Drug: ribavirin; Tablets, oral, 1000 or 1200 mg based on weight, once daily, 24 or 48 weeks depending on response; Other Names: Copegus; Drug: Placebo; Tablets, oral, 0 mg, once daily, 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Extended Rapid Virologic Response (eRVR)	eRVR was defined as HCV RNA <lower limit of quantitation and target not detected at both Weeks 4 and 12 on treatment.	Weeks 4 and 12
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Sustained Virologic Response (SVR24)	SVR24 was defined as HCV <lower limit of quantitation (LLOQ) and target not detected (TND) at follow-up Week 24. The LLOQ was 25 IU/mL, and <LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.	Follow-up Week 24
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died	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.	From start of study treatment (day 1) up to follow-up Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Rapid Virologic Response (RVR)	RVR was defined as undetectable RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at Week 4. The LLOQ was 25 IU/mL, and <LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. N=Number of participants analyzed for this outcome.	Week 4
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Complete Early Virologic Response (cEVR)	cEVR was defined as undetectable RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at Week 12. The LLOQ was 25 IU/mL, and <LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. N=Number of participants analyzed for this outcome.	Week 12
Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With 12-week Sustained Virologic Response (SVR12)	SVR12 was defined as undetectable RNA (HCV RNA < lower limit of quantitation (LLOQ), target not detected (TND) at follow-up Week 12. The LLOQ was 25 IU/mL, and <LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. N=Number of participants analyzed for this outcome.	Follow-up Week 12
Percentage of Resistant Variants Associated With Virologic Failure	Virologic failure was defined as: Virologic breakthrough: confirmed >1 log10 increase in hepatitis C virus (HCV) RNA over nadir or confirmed RNA ≥lower limit of quantitation (LLOQ) after confirmed HCV RNA <LLOQ, target not detected (TND) while on treatment; <1 log10 decrease in HCV RNA from baseline at Week 4 of treatment; Failure to achieve early virologic response: <2 log10 decrease in HCV RNA from baseline and HCV RNA ≥LLOQ at Week 12 of treatment; HCV RNA < LLOQ, TD or ≥ LLOQ at Week 12 and ≥ LLOQ at Week 24; HCV RNA ≥LLOQ or <LLOQ, target detected (TD) at the end of treatment (EOT) (including early discontinuation); Relapse, defined as HCV RNA ≥LLOQ or <LLOQ, TD during follow-up, after HCV RNA < LLOQ, TND at EOT. The LLOQ was 25 IU/mL, and <LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. N=Number of participants analyzed for this outcome.	Follow-up Week 48

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Hezode C, Hirschfield GM, Ghesquiere W, Sievert W, Rodriguez-Torres M, Shafran SD, Thuluvath PJ, Tatum HA, Waked I, Esmat G, Lawitz EJ, Rustgi VK, Pol S, Weis N, Pockros PJ, Bourliere M, Serfaty L, Vierling JM, Fried MW, Weiland O, Brunetto MR, Everson GT, Zeuzem S, Kwo PY, Sulkowski M, Brau N, Hernandez D, McPhee F, Wind-Rotolo M, Liu Z, Noviello S, Hughes EA, Yin PD, Schnittman S. Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: a randomised study. Gut. 2015 Jun;64(6):948-56. doi: 10.1136/gutjnl-2014-307498. Epub 2014 Jul 30.

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: May 17, 2010
• First Submitted That Met QC Criteria: May 17, 2010
• First Posted (Estimate): May 18, 2010

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; Hepatitis; Hepatitis C; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Ribavirin; Peginterferon alfa-2a; Interferon alpha-2
• Other Study ID Numbers: AI444-010; 2010-018295-24 (EudraCT Number)