Study in Genotype 2 or 3 Patients With Chronic Hepatitis Virus Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01257204
First received: December 1, 2010
Last updated: November 10, 2015
Last verified: November 2015
  Purpose
To identify a shorter duration of antiviral therapy (12 or 16 weeks) for the combination of daclatasvir with pegylated interferon alfa-2a and ribavirin.

Condition Intervention Phase
Hepatitis C Virus
Drug: Placebo
Drug: Daclatasvir
Drug: Pegylated interferon alfa-2a
Drug: Ribavirin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2B Pilot Study of Short-Term Treatment of BMS-790052 in Combination With Peg-Interferon Alfa-2a and Ribavirin in Treatment Naive Subjects With Chronic Hepatitis C Genotype 2 or 3 Infection

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 2 [ Time Frame: Follow-up Week 24 ] [ Designated as safety issue: No ]
    SVR24 was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], 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.

  • Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 3 [ Time Frame: Follow-up Week 24 ] [ Designated as safety issue: No ]
    SVR24 was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], 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.


Secondary Outcome Measures:
  • Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 2 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    RVR was defined as undetectable HCV 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.

  • Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 3 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    RVR was defined as undetectable HCV 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.

  • Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 2 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    cEVR was defined as undetectable HCV 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.

  • Percentage of Participants Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 3 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    cEVR was defined as undetectable HCV 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.

  • Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 2 [ Time Frame: Follow-up Week 12 ] [ Designated as safety issue: No ]
    SVR12 was defined as undetectable HCV 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.

  • Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 3 [ Time Frame: Follow-up Week 12 ] [ Designated as safety issue: No ]
    SVR12 was defined as undetectable HCV 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.

  • Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 2 [ Time Frame: Baseline up to Week 48 ] [ Designated as safety issue: No ]

    Virologic failure was defined as:

    1. Virologic breakthrough: confirmed >1 log10 increase in 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 or <LLOQ, target detected (TD) at the end of treatment (EOT) (including early discontinuation)
    5. 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.


  • Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3 [ Time Frame: Baseline up to Week 48 ] [ Designated as safety issue: No ]

    Virologic failure was defined as:

    1. Virologic breakthrough: confirmed >1 log10 increase in 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 or <LLOQ, target detected (TD) at the end of treatment (EOT) (including early discontinuation)
    5. 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.


  • Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period [ Time Frame: Baseline (Day 1) up to 24 weeks (treatment period) ] [ 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 has a causal relationship with treatment. 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. Treatment-related AE was defined as an AE that had certain, probable, possible, or unknown relationship to study drug. Mild (Grade 1): awareness of event but easily tolerated; Moderate (Grade 2): discomfort enough to cause some interference with usual activity; Severe (Grade 3): inability to carry out usual activity; Very severe (Grade 4): debilitating, significantly incapacitates participant despite symptomatic therapy. Only Grade 2-4 treatment-related AEs were reported.

  • Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died During Follow-up Period [ Time Frame: From end of treatment period up to Week 48 (follow-up period) ] [ 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 has a causal relationship with treatment. 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.


Enrollment: 196
Study Start Date: December 2010
Study Completion Date: September 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Control
Placebo + Pegylated interferon alfa-2a + Ribavirin
Drug: Placebo
Tablets, oral, 0 mg, once daily, for 24 weeks
Drug: Pegylated interferon alfa-2a
Solution for injection, subcutaneous injection, 180 µg/0.5 mL, once weekly, for 12, 16, or 24 weeks
Other Name: Pegasys®
Drug: Ribavirin
Tablets, oral, 800 mg, twice daily, for 12, 16, or 24 weeks
Other Name: Copegus®
Experimental: 12 Week Cohort
Daclatasvir + Pegylated interferon alfa-2a + Ribavirin
Drug: Daclatasvir
Tablets, oral, 60 mg, once daily, for 12, 16, or 24 weeks
Other Name: BMS-790052
Drug: Pegylated interferon alfa-2a
Solution for injection, subcutaneous injection, 180 µg/0.5 mL, once weekly, for 12, 16, or 24 weeks
Other Name: Pegasys®
Drug: Ribavirin
Tablets, oral, 800 mg, twice daily, for 12, 16, or 24 weeks
Other Name: Copegus®
Experimental: 16 Week Cohort
Daclatasvir + Pegylated interferon alfa-2a + Ribavirin
Drug: Daclatasvir
Tablets, oral, 60 mg, once daily, for 12, 16, or 24 weeks
Other Name: BMS-790052
Drug: Pegylated interferon alfa-2a
Solution for injection, subcutaneous injection, 180 µg/0.5 mL, once weekly, for 12, 16, or 24 weeks
Other Name: Pegasys®
Drug: Ribavirin
Tablets, oral, 800 mg, twice daily, for 12, 16, or 24 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

Key Inclusion Criteria:

  • Participants chronically infected with hepatitis C virus (HCV) genotype 2 or 3
  • No previous exposure to an interferon formulation (ie, interferon alfa, pegylated interferon alfa-2a ) or ribavirin
  • Body mass index (BMI) of 18 to 35 kg/m^2, inclusive. BMI=weight (kg)/height (m)^2
  • Males and females, 18 - 70 years of age

Key Exclusion Criteria:

  • Liver transplant recipients
  • Documented or suspected hepatocellular carcinoma
  • Evidence of decompensated cirrhosis
  • History of chronic hepatitis B virus (HBV). Patients with resolved HBV infection may participate
  • Current or known history of cancer
  • Any gastrointestinal disease or surgical procedure that may impact the absorption of study drug
  • Inability to tolerate oral medication
  • Poor venous access
  • Severe psychiatric disease
  • History of chronic pulmonary disease
  • History of cardiomyopathy, coronary artery disease (including angina), interventive procedure for coronary artery disease (including angioplasty, stent procedure, or cardiac bypass surgery), ventricular arrhythmia,, or other clinically significant cardiac disease
  • History of or current electrocardiogram findings indicative of cardiovascular instability
  • Preexisting ophthalmologic disorders considered clinically significant on eye
  • History of uncontrolled diabetes mellitus
  • Any known contraindication to pegylated interferon alfa-2a or ribavirin not otherwise specified.
  • Positive hepatitis B virus surface antigen, HIV-1 or HIV-2 Ab
  • Prior exposure to any HCV direct antiviral agent (eg, HCV protease, polymerase, previous nonstructural protein 5A inhibitors)
  • Exposure to any investigational drug or placebo
  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: NCT01257204

  Show 26 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01257204     History of Changes
Other Study ID Numbers: AI444-031  2010-022408-28 
Study First Received: December 1, 2010
Results First Received: August 5, 2015
Last Updated: November 10, 2015
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Biological and Radiopharmaceutical Drugs
Denmark: Lægemiddelstyrelsen
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: Istituto Superiore di Sanità (ISS)
United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 23, 2016