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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01125189
First received: May 17, 2010
Last updated: September 23, 2015
Last verified: September 2015
  Purpose
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.

Condition Intervention Phase
Hepatitis C Virus
Drug: Daclatasvir
Drug: Placebo
Drug: peg-interferon 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, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Extended Rapid Virologic Response (eRVR) [ Time Frame: Weeks 4 and 12 ] [ Designated as safety issue: No ]
    eRVR was defined as HCV RNA <lower limit of quantitation and target not detected at both Weeks 4 and 12 on treatment.

  • Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Sustained Virologic Response (SVR24) [ Time Frame: Follow-up Week 24 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Who Died [ Time Frame: From start of study treatment (day 1) up to follow-up Week 48 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Rapid Virologic Response (RVR) [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With Complete Early Virologic Response (cEVR) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Hepatitis C Virus (HCV) Genotype 1 Participants With 12-week Sustained Virologic Response (SVR12) [ Time Frame: Follow-up Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Resistant Variants Associated With Virologic Failure [ Time Frame: Follow-up Week 48 ] [ Designated as safety issue: No ]

    Virologic failure was defined as:

    1. 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
    2. <1 log10 decrease in HCV RNA from baseline at Week 4 of treatment
    3. Failure to achieve early virologic response: <2 log10 decrease in HCV RNA from baseline and HCV RNA ≥LLOQ at Week 12 of treatment
    4. HCV RNA < LLOQ, TD or ≥ LLOQ at Week 12 and ≥ LLOQ at Week 24
    5. HCV RNA ≥LLOQ or <LLOQ, target detected (TD) at the end of treatment (EOT) (including early discontinuation)
    6. 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.



Enrollment: 558
Study Start Date: July 2010
Study Completion Date: August 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: peg-interferon alfa-2a
Syringe, subcutaneous Injection, 180 µg, once weekly, 24 or 48 weeks depending on response
Other Name: Pegasys
Drug: ribavirin
Tablets, oral, 1000 or 1200 mg based on weight, once daily, 24 or 48 weeks depending on response
Other Name: Copegus
Experimental: Daclatasvir plus peg-interferon alfa-2a and ribavirin (60 mg) 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 Name: Pegasys
Drug: ribavirin
Tablets, oral, 1000 or 1200 mg based on weight, once daily, 24 or 48 weeks depending on response
Other Name: Copegus
Placebo Comparator: Placebo plus peg-interferon alfa-2a and ribavirin Drug: Placebo
Tablets, oral, 0 mg, once daily, 24 weeks
Drug: peg-interferon alfa-2a
Syringe, subcutaneous Injection, 180 µg, once weekly, 24 or 48 weeks depending on response
Other Name: Pegasys
Drug: ribavirin
Tablets, oral, 1000 or 1200 mg based on weight, once daily, 24 or 48 weeks depending on response
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:

  • 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
  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: NCT01125189

  Show 64 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01125189     History of Changes
Other Study ID Numbers: AI444-010  2010-018295-24 
Study First Received: May 17, 2010
Results First Received: August 13, 2015
Last Updated: September 23, 2015
Health Authority: 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: Danish Medicines Agency
Denmark: The Danish National Committee on Biomedical Research Ethics
Egypt: National Ethic Committee
Egypt: Ministry of Health, Drug Policy and Planning Center
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
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: Ministry of Health
Italy: National Bioethics Committee
Italy: National Institute of Health
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: Food and Drug Administration

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

ClinicalTrials.gov processed this record on February 10, 2016