Safety and Efficacy of Daclatasvir (BMS-790052) Plus Standard of Care (Pegylated-interferon Alpha and Ribavirin)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00874770
First received: April 2, 2009
Last updated: September 23, 2015
Last verified: September 2015
  Purpose
The purpose of this study is to identify 1 or more doses of daclatasvir, which when used in combination with pegylated interferon alpha and ribavirin, are safe and demonstrate sufficient anti-hepatitis C virus activity.

Condition Intervention Phase
Hepatitis C Infection
Drug: Daclatasvir
Drug: Placebo
Drug: Peginterferon alpha-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 2a Study of BMS-790052 in Combination With Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®) in Treatment Naive Subjects With Chronic Hepatitis C Virus Genotype 1

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) at Weeks 4 and 12 [ Time Frame: A Weeks 4 and 12 ] [ Designated as safety issue: Yes ]
    eRVR was defined as undetectable hepatitis C virus RNA less than the lower limit of detection (10 IU/mL) at Weeks 4 and 12.


Secondary Outcome Measures:
  • Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 [ Time Frame: At Week 4 ] [ Designated as safety issue: No ]
    RVR was defined as undetectable hepatitis C virus (HCV) RNA ie, HCV RNA less than the lower limit of detection (10 IU/mL) at Week 4.

  • Percentage of Participants With Early Virologic Response (EVR) at Week 12 [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
    EVR was defined as a ≥2 log10 decrease in hepatitis C virus (HCV) RNA from baseline at Week 12 , or HCV RNA <10 IU/mL for participants with baseline HCV RNA <1000 IU/mL.

  • Percentage of Participants With a Complete Early Virologic Response (cEVR) at Week 12 [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
    cEVR was defined as hepatitis C virus RNA <10 IU/mL at Week 12


Other Outcome Measures:
  • Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Treatment-related AEs and Who Died in Treatment Phase [ Time Frame: SAE: From Day 1 up to 30 days after last dose of study drug, AE: From Day 1 to 7 days after last dose of study drug ] [ Designated as safety issue: Yes ]
    An AE was defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a patient or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this 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.

  • Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), and Treatment-related AEs and Who Died in Follow-up Period [ Time Frame: From Day 31 up to Week 24 of post treatment follow-up ] [ Designated as safety issue: Yes ]
    An AE was defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a patient or clinical investigation participant administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this 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.

  • Number of Participants With Grade 3 to 4 Abnormalities on Laboratory Test Results [ Time Frame: From screening up to Week 12 (treatment period) ] [ Designated as safety issue: Yes ]
    Clinically significant change in marked laboratory abnormalities (Grade 3 to 4 ) included: Alanine aminotransferase (ALT)- Grade 3 as >5.0 to 10.0* Upper Limit of Normal (ULN), Grade 4 as >10.0*ULN; Aspartate aminotransferase (AST)- Grade 3 as >5.0 to 10.0*ULN, Grade 4 as >10.0*ULN; Hemoglobin- Grade 3 as 7.0 to 8.9 g/dL, Grade 4 as <7.0 g/dL; Neutrophils- Grade 3 as 0.5 to 0.749*10^9/L, Grade 4 as <0.5*10^9/L; Lymphocytes- Grade 3 as 0.35 to 0.499*10^9/L, Grade 4 as <0.35*10^9/L; Total Bilirubin- Grade 3 as 2.6-5.0*ULN, Grade 4 as >5.0*ULN; Platelets- Grade 3 as 25000 to 49999*10^9/L, Grade 4 as <25000 10^9/L and white blood cells (WBC) - Grade 3 as 1000 to 1499*10^9/L, Grade 4 as <1000*10^9/L.


Enrollment: 74
Study Start Date: June 2009
Study Completion Date: January 2011
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Daclatasvir, plus Peginterferon alpha-2a, ribavirin (A)
Active Comparator
Drug: Daclatasvir
Tablets, oral, 3 mg, Daily, 48 weeks
Drug: Peginterferon alpha-2a
Syringe, subcutaneous, 180 µg, Weekly, 48 weeks
Other Name: Pegasys
Drug: ribavirin
Tablet, oral, 1000 or 1200 mg, based on weight, Daily, 48 weeks
Other Name: Copegus
Experimental: Daclatasvir, Peginterferon alpha-2a, ribavirin (B)
Active Comparator
Drug: Daclatasvir
Tablets, oral, 10 mg, Daily, 48 weeks
Drug: Peginterferon alpha-2a
Syringe, subcutaneous, 180 µg, Weekly, 48 weeks
Other Name: Pegasys
Drug: ribavirin
Tablet, oral, 1000 or 1200 mg, based on weight, Daily, 48 weeks
Other Name: Copegus
Experimental: Daclatasvir, Peginterferon alpha-2a, ribavirin (C)
Active Comparator
Drug: Daclatasvir
Tablets, oral, 60 mg, Daily, 48 weeks
Drug: Peginterferon alpha-2a
Syringe, subcutaneous, 180 µg, Weekly, 48 weeks
Other Name: Pegasys
Drug: ribavirin
Tablet, oral, 1000 or 1200 mg, based on weight, Daily, 48 weeks
Other Name: Copegus
Active Comparator: Placebo, Peginterferon alpha-2a, ribavirin (D) Drug: Placebo
Tablet, oral, 0 mg, Daily 48 weeks
Drug: Peginterferon alpha-2a
Syringe, subcutaneous, 180 µg, Weekly, 48 weeks
Other Name: Pegasys
Drug: ribavirin
Tablet, oral, 1000 or 1200 mg, based on weight, Daily, 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

Key Inclusion Criteria:

  • Patients chronically infected with hepatitis C virus (HCV) genotype 1
  • HCV RNA viral load of ≥10*5* IU/mL (100,000 IU/mL) at screening
  • Treatment naive

Key Exclusion Criteria:

  • Women of child-bearing potential
  • Cirrhosis
  • Coinfection with HIV or hepatitis B virus
  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: NCT00874770

Locations
United States, Alabama
Alabama Liver & Digestive Specialists (Alds)
Montgomery, Alabama, United States, 36116
United States, Colorado
University Of Colorado Denver & Hospital
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University School Of Medicine
New Haven, Connecticut, United States, 06520
United States, Maryland
Mercy Medical Center
Baltimore, Maryland, United States, 21202
United States, Massachusetts
Llc Dba The Research Institute
Springfield, Massachusetts, United States, 01107
United States, New York
Veterans Affairs Medical Center
Bronx, New York, United States, 10468
United States, North Carolina
Carolinas Center For Liver Disease
Statesville, North Carolina, United States, 28677
United States, Oklahoma
Options Health Research, Llc
Tulsa, Oklahoma, United States, 74104
Healthcare Research Consultants
Tulsa, Oklahoma, United States, 74135
United States, Texas
North Texas Research Institute
Arlington, Texas, United States, 76012
United States, Virginia
Metropolitan Research
Fairfax, Virginia, United States, 22031
France
Local Institution
Creteil, France, 94010
Local Institution
Paris Cedex 14, France, 75679
Local Institution
Vandoeuvre Les Nancy, France, 54511
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: NCT00874770     History of Changes
Other Study ID Numbers: AI444-014  EUDRACT# 2009-010149-29 
Study First Received: April 2, 2009
Results First Received: August 6, 2015
Last Updated: September 23, 2015
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
France: Ministry of Health

Keywords provided by Bristol-Myers Squibb:
Antivirals

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 August 23, 2016