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Safety and Efficacy Study in Subjects With Chronic HCV and Underlying Hemophilia

Phase 3
Completed
Conditions
Hepatitis C Virus
Interventions
Biological: Pegylated-Interferon-lambda
Registration Number
NCT01741545
Lead Sponsor
Bristol-Myers Squibb
Brief Summary

The primary objective for this study is to evaluate the proportion of subjects who achieve SVR12 (HCV RNA \< LLOQ (target not detected) at post-treatment follow-up Week 12 in subjects with Genotype(GT)-1b, -4 and GT-2, -3

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
71
Inclusion Criteria
  • Severe hemophilia (defined as < 1% factor activity level)
  • Infection with the hepatitis C virus (HCV) with underlying hemophilia
  • Males 18 years of age and above
  • Have not been previously treated with an interferon
Exclusion Criteria
  • Not infected with the hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
  • Chronic liver disease caused by any disease other than chronic HCV infection
  • Presence of Bethesda inhibitor
  • Current evidence of or history of portal hypertension

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort A: Genotype-2,-3 (Lambda/RBV/DCV)RibavirinLambda 180 μg solution for subcutaneous (SC) injection, once weekly for 12 weeks Ribavirin (RBV) 200 mg tablet by mouth (oral), twice daily for 12 weeks Daclatasvir (DCV) 60mg tablet by mouth (oral), once daily for 12 weeks
Cohort B: Genotype-1b,-4 (Lambda/RBV/DCV)Pegylated-Interferon-lambdaLambda 180 μg solution for subcutaneous (SC) injection, once weekly for 24 weeks Ribavirin (RBV) 200 mg tablet by mouth (oral), twice daily for 24 weeks Daclatasvir (DCV) 60mg tablet by mouth (oral), once daily for 12 weeks
Cohort A: Genotype-2,-3 (Lambda/RBV/DCV)Pegylated-Interferon-lambdaLambda 180 μg solution for subcutaneous (SC) injection, once weekly for 12 weeks Ribavirin (RBV) 200 mg tablet by mouth (oral), twice daily for 12 weeks Daclatasvir (DCV) 60mg tablet by mouth (oral), once daily for 12 weeks
Cohort B: Genotype-1b,-4 (Lambda/RBV/DCV)DaclatasvirLambda 180 μg solution for subcutaneous (SC) injection, once weekly for 24 weeks Ribavirin (RBV) 200 mg tablet by mouth (oral), twice daily for 24 weeks Daclatasvir (DCV) 60mg tablet by mouth (oral), once daily for 12 weeks
Cohort A: Genotype-2,-3 (Lambda/RBV/DCV)DaclatasvirLambda 180 μg solution for subcutaneous (SC) injection, once weekly for 12 weeks Ribavirin (RBV) 200 mg tablet by mouth (oral), twice daily for 12 weeks Daclatasvir (DCV) 60mg tablet by mouth (oral), once daily for 12 weeks
Cohort B: Genotype-1b,-4 (Lambda/RBV/DCV)RibavirinLambda 180 μg solution for subcutaneous (SC) injection, once weekly for 24 weeks Ribavirin (RBV) 200 mg tablet by mouth (oral), twice daily for 24 weeks Daclatasvir (DCV) 60mg tablet by mouth (oral), once daily for 12 weeks
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Who Achieved Sustained Virologic Response (SVR12) at Follow-Up Week 12Follow-up Week 12

SVR12 was defined as HCV ribonucleic acid (RNA) less than the lower limit of quantitation, target detected or target not detected at follow-up Week 12.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Flu-Like Symptoms and Musculoskeletal Symptoms On-TreatmentAfter day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)

Flu-like symptoms were defined as pyrexia or chills or pain. Musculoskeletal symptoms were defined as arthralgia or myalgia or back pain.

Percentage of Participants With Complete Early Virologic Response (cEVR)Treatment Week 12

cEVR was defined as HCV RNA less than the lower limit of quantitation, target not detected at Week 12.

Percentage of Participants With Rapid Virologic Response (RVR)Treatment Week 4

RVR was defined as HCV RNA less than the lower limit of quantitation, target not detected at Week 4.

Percentage of Participants With End of the Treatment Response (EOTR)End of the treatment (Week 12 for Cohort A, Week 24 for Cohort B)

EOTR was defined as HCV RNA less than the lower limit of quantitation, target not detected at end of treatment.

Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory AbnormalitiesAfter day 1 to to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)

Laboratory abnormalities were determined and graded using the Division of acquired immunodeficiency syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, version 1.0. International Normalized Ratio (INR): \>2.0\*Upper limit of normal (ULN); Alanine aminotransferase (ALT) : \>5\*ULN; Aspartate aminotransferase (AST): \>5\*ULN; Prothrombin Time (PT): \>1.50\*ULN; Bilirubin (Total): \>2.5\*ULN; Triglycerides (fasting): \>750 mg/dL.

Percentage of Participants With Sustained Virologic Response at Follow-Up Week 24 (SVR24)Follow-up Week 24

SVR24 was defined as HCV RNA less than the lower limit of quantitation, target detected or target not detected at follow-up week 24.

Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And DeathFrom Day 1 to end of follow-up (maximum of 60 weeks for Cohort A and 72 weeks for Cohort B)

AE=any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Treatment-related SAE=possibly, probably, or certainly related to study drug.

Percentage of Participants With Treatment-Emergent Cytopenic Abnormalities On-TreatmentAfter day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B)

Cytopenic abnormalities were defined as anemia: Hemoglobin (Hb) \<10 g/dL, and/or neutropenia: absolute neutrophils and bands (ANC) \<750 mm\^3, and/or thrombocytopenia: platelets \<50,000 mm\^3.

Trial Locations

Locations (5)

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

Hospital Of The University Of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Stanford Boswell Clinic

🇺🇸

Palo Alto, California, United States

Clinical Research Centers Of America

🇺🇸

Murray, Utah, United States

Local Institution

🇪🇸

Sevilla, Spain

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