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

May 17, 2010
September 23, 2015
July 2010
April 2012   (final data collection date for primary outcome measure)
  • 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.
  • Antiviral activity, as determined by the proportion of HCV genotype 1 subjects with extended rapid virologic response, defined as undetectable HCV RNA [ Time Frame: Weeks 4 and 12 ] [ Designated as safety issue: No ]
  • Antiviral activity, as determined by the proportion of HCV genotype 1 subjects with 24-week sustained virologic response, defined as undetectable HCV RNA [ Time Frame: Follow-up Week 24 ] [ Designated as safety issue: No ]
  • Safety, as measured by the frequency of Serious Adverse Events and discontinuations due to Adverse Events [ Time Frame: Week 12, Week 24, and follow-up Week 12 ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01125189 on ClinicalTrials.gov Archive Site
  • 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.

  • To assess the proportion of HCV genotype 1 subjects with rapid virologic response, ie, undetectable HCV RNA [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
  • To assess the proportion of HCV genotype 1 subjects with complete early virologic response, ie, undetectable HCV RNA [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • To assess the proportion of HCV genotype 1 subjects with 12-week sustained virologic response, ie, undetectable HCV RNA [ Time Frame: Follow-up Week 12 ] [ Designated as safety issue: No ]
  • To describe resistant variants associated with virologic failure [ Time Frame: Follow-up Week 48 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study of Daclatasvir (BMS-790052) Add-on to Standard of Care in Treatment- naïve Patients
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.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hepatitis C Virus
  • 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: 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
  • Experimental: Daclatasvir plus peg-interferon alfa-2a and ribavirin (20 mg)
    Interventions:
    • Drug: Daclatasvir
    • Drug: peg-interferon alfa-2a
    • Drug: ribavirin
  • Experimental: Daclatasvir plus peg-interferon alfa-2a and ribavirin (60 mg)
    Interventions:
    • Drug: Daclatasvir
    • Drug: peg-interferon alfa-2a
    • Drug: ribavirin
  • Placebo Comparator: Placebo plus peg-interferon alfa-2a and ribavirin
    Interventions:
    • Drug: Placebo
    • Drug: peg-interferon alfa-2a
    • Drug: ribavirin
Hézode 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, Bourlière M, Serfaty L, Vierling JM, Fried MW, Weiland O, Brunetto MR, Everson GT, Zeuzem S, Kwo PY, Sulkowski M, Bräu 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
558
August 2012
April 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 70 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   Denmark,   Egypt,   France,   Germany,   Italy,   Mexico,   Puerto Rico,   Sweden
 
NCT01125189
AI444-010, 2010-018295-24
No
Not Provided
Not Provided
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP