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

Study Overview
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Brief Summary
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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

Official Title
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A Phase 3 Study Evaluating the Safety and Efficacy of Lambda/Ribavirin/Daclatasvir in Subjects With Chronic HCV Infection and Underlying Hemophilia Who Are Treatment Naïve or Are Prior Relapsers to Peginterferon Alfa-2a/Ribavirin

Conditions
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Hepatitis C Virus

Intervention / Treatment
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* Biological: Pegylated-Interferon-lambda
* Drug: Ribavirin
* Drug: Daclatasvir


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Genotype-2,-3 (Lambda/RBV/DCV)<br>Lambda 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 | Biological: Pegylated-Interferon-lambda<br> <br> * Other names: BMS-914143;Drug: Ribavirin<br> <br> Drug: Daclatasvir<br> <br> * Other names: BMS-790052;|
| Experimental: Cohort B: Genotype-1b,-4 (Lambda/RBV/DCV)<br>Lambda 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 | Biological: Pegylated-Interferon-lambda<br> <br> * Other names: BMS-914143;Drug: Ribavirin<br> <br> Drug: Daclatasvir<br> <br> * Other names: BMS-790052;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Sustained Virologic Response (SVR12) at Follow-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. | Follow-up Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Rapid Virologic Response (RVR) | RVR was defined as HCV RNA less than the lower limit of quantitation, target not detected at Week 4. | Treatment Week 4 | 
| Percentage of Participants With Complete Early Virologic Response (cEVR) | cEVR was defined as HCV RNA less than the lower limit of quantitation, target not detected at Week 12. | Treatment Week 12 | 
| Percentage of Participants With End of the Treatment Response (EOTR) | EOTR was defined as HCV RNA less than the lower limit of quantitation, target not detected at end of treatment. | End of the treatment (Week 12 for Cohort A, Week 24 for Cohort B) | 
| Percentage of Participants With Sustained Virologic Response at Follow-Up Week 24 (SVR24) | SVR24 was defined as HCV RNA less than the lower limit of quantitation, target detected or target not detected at follow-up week 24. | Follow-up Week 24 | 
| Percentage of Participants With Treatment-Emergent Cytopenic Abnormalities On-Treatment | 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. | After day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B) | 
| Percentage of Participants With Flu-Like Symptoms and Musculoskeletal Symptoms On-Treatment | Flu-like symptoms were defined as pyrexia or chills or pain. Musculoskeletal symptoms were defined as arthralgia or myalgia or back pain. | After day 1 to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B) | 
| Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Dose Reductions, And Death | 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. | From Day 1 to end of follow-up (maximum of 60 weeks for Cohort A and 72 weeks for Cohort B) | 
| Number of Participants With Treatment Emergent Grade 3 to 4 Laboratory Abnormalities | 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. | After day 1 to to end of treatment (Up to 85 Days for Cohort A, Up to 168 Days for Cohort B) |