Safety and Efficacy of Daclatasvir (BMS-790052) Plus Standard of Care (Pegylated-interferon Alpha-2b and Ribavirin) in Japanese Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01016912
First received: November 19, 2009
Last updated: September 23, 2015
Last verified: September 2015
  Purpose
The purpose of this study is to identify at least 1 dose of daclatasvir that is safe, well tolerated, and efficacious when combined with peginterferon-alfa and ribavirin for the treatment of hepatitis C virus genotype 1 in chronically infected patients who are treatment-naïve and nonresponsive to the standard of care

Condition Intervention Phase
Hepatitis C Infection
Drug: BMS-790052
Drug: Placebo
Drug: Peginterferon alfa-2b
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-2b (PegIntron®) and Ribavirin (Rebetol®) in Japanese Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

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: At Weeks 4 and 12 on treatment ] [ Designated as safety issue: Yes ]
    eRVR was defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at both Weeks 4 and 12. HCV RNA levels were measured by Tobas TaqMan HCV Auto from the central laboratory.


Secondary Outcome Measures:
  • Percentage of Participants With Rapid Virologic Response (RVR) [ Time Frame: At Week 4 on treatment ] [ Designated as safety issue: No ]
    RVR was defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at Week 4. HCV RNA levels were measured by CobasTaqMan HCV Auto from the central laboratory .

  • Percentage of Participants With Complete Early Virologic Response (cEVR) [ Time Frame: At Week 12 on treatment ] [ Designated as safety issue: No ]
    cEVR was defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at Week 12 on treatment. HCV RNA levels were measured by Cobas TaqMan HCV Auto from the central laboratory

  • Percentage of Participants With a Sustained Virologic Response (SVR) at Weeks 4, 12, and 24 [ Time Frame: Follow-up Weeks 4, 12, and 24 ] [ Designated as safety issue: No ]
    SVR at follow-up Week 4 (SVR4), follow-up Week 12 (SVR12), and follow-up Week 24 (SVR24) is defined as undetectable hepatitis C virus (HCV) RNA (ie, HCV RNA <15 IU/mL, the lower limit of detection, target not detected) at each of these timepoints. HCV RNA levels were measured by Cobas TaqMan HCV Auto from the central laboratory .

  • Percentage of Participants With Virologic Failure [ Time Frame: From on-treatment Week 1 to Follow-up Week 24 ] [ Designated as safety issue: No ]
    Virologic failure is defined by the following 6 categories: 1.Virologic breakthrough, defined as confirmed >1 log10 increase in hepatitis C virus (HCV) RNA over nadir or confirmed HCV RNA ≥limit of quantitation (LOQ) after confirmed undetectable HCV RNA while on treatment. 2. <1 log10 decrease in HCV RNA from baseline at Week 4 of treatment. 3. Failure to achieve early virologic response, defined as <2 log10 decrease in HCV RNA from baseline at Week 12 of treatment. 4. Detectable HCV RNA at Week 12, and HCV RNA ≥LOQ at Week 24 of treatment. 5. Detectable HCV RNA at end of treatment (including early discontinuation). 6 Relapse, defined as detectable HCV RNA during follow-up after undetectable HCV RNA levels at end of treatment.


Other Outcome Measures:
  • Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs), Treatment-related AEs, and Death as Outcome [ Time Frame: From baseline to 30 days after last dose of study drug ] [ 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.

  • Number of Participants With Grade 3 to 4 Abnormalities on Laboratory Test Results [ Time Frame: From baseline to 30 days after last dose of study drug ] [ Designated as safety issue: Yes ]
    Clinically significant marked abnormalities in laboratory test results graded by the Division of AIDS grading table, 2004. Hemoglobin: Grade 3= <7.0 to 8.9 g/dL, Grade 4= <7.0 g/dL. Lymphocytes: Grade 3= 350-499 cells/mm^3, Grade 4= <350 cells/mm^3. Neutrophils: Grade 3= 500-999 cells/mm^3, Grade 4= <500 cells/mm^3. White blood cells (WBC): Grade 3= 1000-1499 cells/mm^3, Grade 4= <1000 cells/mm^3. Alanine aminotransferase (ALT): Grade 3= 5.1-10*upper limit of normal (ULN), Grade 4= >10.0*ULN. Aspartate aminotransferase (AST): Grade 3= 5.1-10*ULN, Grade 4= >10.0*ULN. Total bilirubin: Grade 3= 2.6-5*ULN, Grade 4= >5.0*ULN.


Enrollment: 51
Study Start Date: December 2009
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (BMS-790052, plus Peginterferon alfa-2b, Ribavirin)
Treatment Naive
Drug: BMS-790052
Tablets, Oral, 10 mg, daily, 24-48 weeks
Drug: Peginterferon alfa-2b
Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks
Other Name: PegIntron®
Drug: Ribavirin
Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks
Other Name: Rebetol®
Experimental: Arm B (BMS-790052, plus Peginterferon alfa-2b, Ribavirin)
Treatment Naive
Drug: BMS-790052
Tablets, Oral, 60 mg, daily, 24-48 weeks
Drug: Peginterferon alfa-2b
Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks
Other Name: PegIntron®
Drug: Ribavirin
Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks
Other Name: Rebetol®
Placebo Comparator: Arm C (Placebo, plus Peginterferon alfa-2b, Ribavirin)
Treatment Naive
Drug: Placebo
Tablets, Oral, 0 mg, daily, 48 weeks
Drug: Peginterferon alfa-2b
Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks
Other Name: PegIntron®
Drug: Ribavirin
Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks
Other Name: Rebetol®
Experimental: Arm D (BMS-790052, plus peginterferon alfa-2b, Ribavirin)
Non-Responder
Drug: BMS-790052
Tablets, Oral, 10 mg, daily, 24-48 weeks
Drug: Peginterferon alfa-2b
Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks
Other Name: PegIntron®
Drug: Ribavirin
Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks
Other Name: Rebetol®
Experimental: Arm E (BMS-790052, plus Peginterferon alfa-2b, Ribavirin)
Non-Responder
Drug: BMS-790052
Tablets, Oral, 60 mg, daily, 24-48 weeks
Drug: Peginterferon alfa-2b
Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks
Other Name: PegIntron®
Drug: Ribavirin
Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks
Other Name: Rebetol®

  Eligibility

Ages Eligible for Study:   20 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 ≥10*5* IU/mL at screening
  • Naïve or nonresponsive to the current standard of care

Key Exclusion Criteria:

  • Cirrhosis
  • Hepatocellular carcinoma
  • Coinfection with hepatitis B virus, HIV-1 or HIV-2
  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: NCT01016912

Locations
Japan
Local Institution
Hiroshima City, Hiroshima, Japan, 734-0037
Local Institution
Sapporo-Shi, Hokkaido, Japan, 060-0033
Local Institution
Kawasaki-Shi, Kanagawa, Japan, 2138587
Local Institution
Suita-Shi, Osaka, Japan, 5650871
Local Institution
Iruma-Gun, Saitama, Japan, 3500495
Local Institution
Minato-Ku, Tokyo, Japan, 105-0001
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: NCT01016912     History of Changes
Other Study ID Numbers: AI444-021 
Study First Received: November 19, 2009
Results First Received: August 17, 2015
Last Updated: September 23, 2015
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Infection
Hepatitis
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Ribavirin
Peginterferon alfa-2b
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 25, 2016