Study of the Anti-HCV Drug (BMS-790052) Combined With Peginterferon and Ribavirin in Patients Who Failed Prior Treatment (HEPCAT)

A Phase 2B Study of BMS-790052 in Combination With Peginterferon Alfa-2a and Ribavirin in Chronic Hepatitis C Genotype 1 Infected Subjects Who Are Null or Partial Responders to Prior Treatment With Peginterferon Alfa Plus Ribavirin Therapy

The purpose of this study is to determine whether BMS-790052 added to Peginterferon Alfa-2a and ribavirin can result in higher cure rates in patients who previously failed therapy and may have limited response to retreatment with Peginterferon Alfa-2a and ribavirin alone.

Study Overview

• Status: Completed
• Conditions: Hepatitis C Virus
• Intervention / Treatment: Drug: BMS-790052; Drug: BMS-790052; Drug: peginterferon alfa-2a; Drug: ribavirin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 512
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad De Buenos Aires, Buenos Aires, Argentina, C1121ABE
      • Local Institution
    • Ciudad De Buenos Aires, Buenos Aires, Argentina, C1181ACH
      • Local Institution
  • Santa Fe
    • Prov De Santa Fe, Santa Fe, Argentina, 2000
      • Local Institution
• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Local Institution
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Local Institution
    • Heidelberg, Victoria, Australia, 3084
      • Local Institution
    • Prahan, Victoria, Australia, 3004
      • Local Institution
  • Western Australia
    • Fremantle, Western Australia, Australia, 6160
      • Local Institution
    • Perth, Western Australia, Australia, 6001
      • 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
• France
  • Clichy Cedex, France, 92118
    • Local Institution
  • Creteil Cedex, France, 94010
    • Local Institution
  • Lyon Cedex 04, France, 69317
    • Local Institution
  • Nice Cedex 03, France, 06202
    • Local Institution
  • Paris Cedex, France, 75013
    • Local Institution
  • Paris Cedex 14, France, 75679
    • Local Institution
  • Vandoeuvre Les Nancy, France, 54511
    • Local Institution
• Germany
  • Essen, Germany, 45122
    • Local Institution
  • Frankfurt, Germany, 60590
    • Local Institution
  • Hamburg, Germany, 20099
    • Local Institution
  • Hannover, Germany, 30625
    • Local Institution
• Italy
  • Cisanello (pisa), Italy, 56124
    • Local Institution
  • Pavia, Italy, 27100
    • Local Institution
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44160
      • Local Institution
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62170
      • Local Institution
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64710
      • Local Institution
• Puerto Rico
  • Ponce, Puerto Rico, 00780
    • Instituto De Investigacion Cientifica Del Sur
  • San Juan, Puerto Rico, 00927
    • Local Institution
• Sweden
  • Gothenburg, Sweden, SE-416 85
    • Local Institution
  • Stockholm, Sweden, 14186
    • 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, 94110
      • University of California at San Francisco
    • San Francisco, California, United States, 94118
      • Kaiser Permanente Medical Center
  • 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, 32610-0277
      • University Of Florida Hepatology
    • 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 Medical Institutions
  • Massachusetts
    • Springfield, Massachusetts, United States, 01105
      • The Research Institute
  • Missouri
    • St. Louis, Missouri, United States, 63104
      • Saint Louis University
  • New York
    • Albany, New York, United States, 12208
      • Samuel S. Stratton Vamc
    • 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
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7584
      • University of North Carolina, Chapel Hill
    • Statesville, North Carolina, United States, 28677
      • Carolinas Center For Liver Disease
  • Oklahoma
    • 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
      • Liver Associates of Texas
    • 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:

• Subjects chronically infected with HCV genotype 1
• Non-responder to prior therapy with peginterferon alfa and ribavirin
• HCV RNA viral load of 100,00 IU/mL
• Results of a liver biopsy ≤ 24 months prior to randomization consistent with chronic HCV infection; for compensated cirrhotics can be any time prior to randomization (compensated cirrhotics biopsy enrollment will be capped at 25% of randomized study population)
• Ultrasound, CT scan or MRI results 12 months prior to randomization that do not demonstrate hepatocellular carcinoma
• Body Mass Index (BMI) of 18 to 35 kg/m2

Exclusion Criteria:

• Positive for Hepatitis B infection (HBsAg) or HIV-1/HIV-2 antibody at screening
• Evidence of 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: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: BMS-790052 plus peginterferon alfa-2a and ribavirin; (prior null responders)	Drug: BMS-790052; Film coated tablet, Oral, 20 mg, once daily, 24 weeks; Drug: BMS-790052; Film coated Tablet, Oral, 60 mg, once daily (divided dose taken BID), 48 weeks; Drug: peginterferon alfa-2a; Solution for injection, Subcutaneous injection, 180 µg, weekly, 24 or 48 weeks; Other Names: Pegasys®; Drug: ribavirin; Film coated tablet, Oral, 1,000 or 1,200 mg based on weight, divided dose taken twice a day (BID), 48 weeks; Other Names: Copegus®
Experimental: Arm 2: BMS-790052 plus peginterferon alfa-2a and ribavirin; (prior null responders)	Drug: BMS-790052; Film coated tablet, Oral, 20 mg, once daily, 24 weeks; Drug: BMS-790052; Film coated Tablet, Oral, 60 mg, once daily (divided dose taken BID), 48 weeks; Drug: peginterferon alfa-2a; Solution for injection, Subcutaneous injection, 180 µg, weekly, 24 or 48 weeks; Other Names: Pegasys®; Drug: ribavirin; Film coated tablet, Oral, 1,000 or 1,200 mg based on weight, divided dose taken twice a day (BID), 48 weeks; Other Names: Copegus®
Experimental: Arm 3: BMS-790052 plus peginterferon alfa-2a and ribavirin; (prior partial responders)	Drug: BMS-790052; Film coated tablet, Oral, 20 mg, once daily, 24 weeks; Drug: BMS-790052; Film coated Tablet, Oral, 60 mg, once daily (divided dose taken BID), 48 weeks; Drug: peginterferon alfa-2a; Solution for injection, Subcutaneous injection, 180 µg, weekly, 24 or 48 weeks; Other Names: Pegasys®; Drug: ribavirin; Film coated tablet, Oral, 1,000 or 1,200 mg based on weight, divided dose taken twice a day (BID), 48 weeks; Other Names: Copegus®
Experimental: Arm 4: BMS-790052 plus peginterferon alfa-2a and ribavirin; (prior partial responders)	Drug: BMS-790052; Film coated tablet, Oral, 20 mg, once daily, 24 weeks; Drug: BMS-790052; Film coated Tablet, Oral, 60 mg, once daily (divided dose taken BID), 48 weeks; Drug: peginterferon alfa-2a; Solution for injection, Subcutaneous injection, 180 µg, weekly, 24 or 48 weeks; Other Names: Pegasys®; Drug: ribavirin; Film coated tablet, Oral, 1,000 or 1,200 mg based on weight, divided dose taken twice a day (BID), 48 weeks; Other Names: Copegus®
Experimental: Arm 5: Placebo plus peginterferon alfa-2a and ribavirin; (prior partial responders only)	Drug: peginterferon alfa-2a; Solution for injection, Subcutaneous injection, 180 µg, weekly, 24 or 48 weeks; Other Names: Pegasys®; Drug: ribavirin; Film coated tablet, Oral, 1,000 or 1,200 mg based on weight, divided dose taken twice a day (BID), 48 weeks; Other Names: Copegus®; Drug: Placebo; Film coated tablet, Oral, 0mg, Once daily, 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Extended Rapid Virologic Response (eRVR)	eRVR was defined as undetectable Hepatitis C virus RNA at both Weeks 4 and 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.	Week 4, Week 12
Percentage of Participants With 24-week Sustained Virologic Response (SVR24)	SVR24 was defined as undetectable RNA (Hepatitis C Virus [HCV] RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at follow-up Week 24. 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 On-treatment	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. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity; or was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization.	From first dose to last dose plus 7 days, up to 49 weeks
Number of Participants With Serious Adverse Events (SAEs) and Who Died 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. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization.	From day 8 post last dose of treatment up-to Week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Rapid Virologic Response (RVR)	RVR was defined as undetectable RNA ie., Hepatitis C virus (HCV) RNA <lower limit of quantitation [LLOQ], target not detected (TND) at Week 4. TND was 10 IU/mL. HCV RNA levels were measured by the Roche Cobas® TaqMan® HCV Test version 2.0 from the central laboratory.	Week 4
Percentage of Participants With Complete Early Virologic Response (cEVR)	cEVR was defined as undetectable RNA ie., Hepatitis C virus (HCV) RNA <lower limit of quantitation [LLOQ], target not detected (TND) at Week 12. TND was 10 IU/mL. HCV RNA levels were measured by the Roche Cobas® TaqMan® HCV Test version 2.0 from the central laboratory.	Week 12
Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12)	SVR12 was defined as undetectable RNA ie., Hepatitis C virus (HCV) RNA <lower limit of quantitation (LLOQ), target not detected (TND) at follow-up Week 12. 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 12
Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures	Non-structural protein 5A of HCV resistance associated polymorphism in GT-1a samples included M28L/T/V, Q30H, L31M, H54Y, H58C/D/N/P/Q, E62D and Y93C.	Baseline to follow-up Week 48
Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures	Non-structural protein 5A of HCV resistance associated polymorphisms in GT-1b samples, included L28M/V, R30H/Q, L31M, Q54H/N/Y, P58A/Q/S, Q62E/K/N/R/S, A92T/V and Y93F/H.	Baseline to follow-up Week 48

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: July 16, 2010
• First Submitted That Met QC Criteria: July 26, 2010
• First Posted (Estimate): July 28, 2010

Study Record Updates

• Last Update Posted (Estimate): October 12, 2015
• Last Update Submitted That Met QC Criteria: September 11, 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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Peginterferon alfa-2a
• Other Study ID Numbers: AI444-011; 2010-019378-34 (EudraCT Number)