Safety and Efficacy Study of the Combination Daclatasvir (60 mg), Sofosbuvir (400 mg) and Ribavirin (Weight-based Dosing) for 12 or 16 Weeks in Subjects With Genotype 3 Chronic HCV Infection With or Without Prior Treatment Experience and Advanced Fibrosis or Compensated Cirrhosis

Study Overview
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Brief Summary
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The purpose of the study is to determine if the combination of Daclatasvir, Sofosbuvir and Ribavirin for 12 or 16 weeks is safe and effective in the treatment of Genotype 3 Chronic Hepatitis C (HCV) in patients with advanced fibrosis or compensated cirrhosis. Patients in this study may have already been treated prior for HCV or may have never received treatment for their HCV.

Official Title
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Open-Label, Randomized Study of Daclatasvir, Sofosbuvir, and Ribavirin for 12 vs. 16 Weeks in Treatment Naive and Treatment Experienced Patients With Genotype 3 Chronic Hepatitis C Infection Subjects With Compensated Advanced Fibrosis/Cirrhosis (F3/F4)

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Daclatasvir
* Drug: Sofosbuvir
* Drug: Ribavirin


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: Must have Genotype 3 Chronic HCV Must have advanced fibrosis (F3) or compensated cirrhosis (F4) HCV RNA Viral load ≥ 10,000 IU/mL HCV Treatment naive or treatment-experienced Exclusion Criteria: Non Genotype 3 or mixed genotypes Non advanced fibrosis or compensated cirrhosis Any prior treatment with NS5A inhibitors

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm1: Daclatasvir + Sofosbuvir + Ribavirin (12 Weeks)<br>Oral dosing Daclatasvir 60mg once daily, Sofosbuvir 400mg once daily, and Ribavirin 1000-1200mg (weight based dosing) split into am and pm dosing | Drug: Daclatasvir<br> <br> Drug: Sofosbuvir<br> <br> Drug: Ribavirin<br> <br> |
| Active Comparator: Arm2 : Daclatasvir + Sofosbuvir + Ribavirin (16 Weeks)<br>Oral dosing Daclatasvir 60mg once daily, Sofosbuvir 400mg once daily, and Ribavirin 1000-1200mg (weight based dosing) split into am and pm dosing | Drug: Daclatasvir<br> <br> Drug: Sofosbuvir<br> <br> Drug: Ribavirin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With a Sustained Virologic Response (SVR) at Follow-up Week 12 (SVR12) | SVR12, defined as percentage of participants with hepatitis C virus (HCV) ribonucleic acid (RNA) < lower limit of quantitation (LLOQ), target detected (TD) or target not detected (TND) at follow-up Week 12. SVR12 imputation was based on Next Value Carried Backwards (NVCB) approach. HCV RNA measurements were excluded after the start of non-study anti-HCV medication on treatment or during follow-up. | Follow-up Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With a Sustained Virologic Response (SVR) at Follow-up Week 4 (SVR4) and Follow-up Week 24 (SVR24) | SVR4, defined as percentage of participants with hepatitis C virus (HCV) ribonucleic acid (RNA) < lower limit of quantitation (LLOQ), target detected (TD) or target not detected (TND) at follow-up Week 4. SVR24, defined as percentage of participants with hepatitis C virus (HCV) ribonucleic acid (RNA) < lower limit of quantitation (LLOQ), target detected (TD) or target not detected (TND) at follow-up Week 24. SVR4 imputation was based on Next Value Carried Backwards (NVCB) approach. SVR24 imputation was based on missing being treated as non-responder. HCV RNA measurements were excluded after the start of non-study anti-HCV medication on treatment or during follow-up. | Follow-up Weeks 4 and 24 | 
| Number of Participants With Death, Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), Grade 3 or Grade 4 (Grade 3/4) AEs, and Grade 3/4 Laboratory Abnormalities | Serious adverse event (SAE) defined: a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. The degree of the adverse event or laboratory abnormality are evaluated by grades: Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. Grading as per using National Cancer Institute Common Terminology Criteria (NCI CTC) Version 3.0 criteria. | Date of First Dose of Study Drug to 7 Days post last dose of study drug (up to 13 weeks or 17 weeks depending on the randomized treatment group) |