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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01170962
First received: July 16, 2010
Last updated: September 11, 2015
Last verified: September 2015
  Purpose
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.

Condition Intervention Phase
Hepatitis C Virus
Drug: BMS-790052
Drug: Placebo
Drug: peginterferon alfa-2a
Drug: ribavirin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Percentage of Participants With Extended Rapid Virologic Response (eRVR) [ Time Frame: Week 4, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With 24-week Sustained Virologic Response (SVR24) [ Time Frame: Follow-up Week 24 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs) and Who Died On-treatment [ Time Frame: From first dose to last dose plus 7 days, up to 49 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. 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.

  • Number of Participants With Serious Adverse Events (SAEs) and Who Died During Follow-up Period [ Time Frame: From day 8 post last dose of treatment up-to Week 72 ] [ 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. 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.


Secondary Outcome Measures:
  • Percentage of Participants With Rapid Virologic Response (RVR) [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Complete Early Virologic Response (cEVR) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) [ Time Frame: Follow-up Week 12 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures [ Time Frame: Baseline to follow-up Week 48 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures [ Time Frame: Baseline to follow-up Week 48 ] [ Designated as safety issue: No ]
    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.


Enrollment: 512
Study Start Date: August 2010
Study Completion Date: December 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: peginterferon alfa-2a
Solution for injection, Subcutaneous injection, 180 µg, weekly, 24 or 48 weeks
Other Name: 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 Name: Copegus®
Experimental: Arm 2: BMS-790052 plus peginterferon alfa-2a and ribavirin
(prior null responders)
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 Name: 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 Name: 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: peginterferon alfa-2a
Solution for injection, Subcutaneous injection, 180 µg, weekly, 24 or 48 weeks
Other Name: 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 Name: Copegus®
Experimental: Arm 4: BMS-790052 plus peginterferon alfa-2a and ribavirin
(prior partial responders)
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 Name: 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 Name: Copegus®
Experimental: Arm 5: Placebo plus peginterferon alfa-2a and ribavirin
(prior partial responders only)
Drug: Placebo
Film coated tablet, Oral, 0mg, Once daily, 24 weeks
Drug: peginterferon alfa-2a
Solution for injection, Subcutaneous injection, 180 µg, weekly, 24 or 48 weeks
Other Name: 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 Name: Copegus®

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01170962

  Show 72 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01170962     History of Changes
Other Study ID Numbers: AI444-011  2010-019378-34 
Study First Received: July 16, 2010
Results First Received: August 10, 2015
Last Updated: September 11, 2015
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: National Health and Medical Research Council
Canada: Health Canada
Canada: Regulatory Affairs Division Office of Clinical Trials Therapeutic Products Directorate
Denmark: Danish Dataprotection Agency
Denmark: The Danish National Committee on Biomedical Research Ethics
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ministry of Health
Italy: National Bioethics Committee
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: The Italian Medicines Agency
Mexico: Federal Commission for Sanitary Risks Protection
Sweden: Medical Products Agency
Sweden: The National Board of Health and Welfare
Sweden: The Swedish Data Inspection Board
Sweden: Central Ethics Board
United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Ribavirin
Peginterferon alfa-2a
Interferon-alpha
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 21, 2016