Safety and Efficacy Study of Daclatasvir (BMS-790052) Plus Pegylated Interferon-Alfa 2a and Ribavirin in Patients Coinfected With Untreated Hepatitis C Virus and HIV Virus

Study Overview
=================
Brief Summary
-----------------
The purpose of this open label study is to evaluate the safety and efficacy of daclatasvir plus pegylated interferon-alfa 2a and ribavirin in untreated hepatitis C virus in patients coinfected with HIV

Official Title
-----------------
A Phase 3, Open Label Study of Safety and Efficacy With BMS-790052 Plus Peg-Interferon Alfa 2a and Ribavirin in Previously Untreated HCV Patients Coinfected With Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV)

Conditions
-----------------
Hepatitis C, Genotype 1

Intervention / Treatment
-----------------
* Drug: Daclatasvir
* Drug: Ribavirin
* Drug: PEG-Interferon alfa 2a


Participation Criteria
=================
Eligibility Criteria
-----------------
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Key Inclusion Criteria: Males and females, 18 to 70 years of age Hepatitis C virus (HCV) genotype 1a or 1b HCV-treatment naive HCV RNA >10,000 IU/mL at screening HIV-1 infection (approximately 250 patients receiving highly active antiretroviral therapy [HAART], up to 50 patients not receiving HAART) For patients receiving HAART, HIV RNA must be below <40 copies/mL at screening and must be <400 copies/ml for at least 6 months prior to screening Key Exclusion Criteria: Patients receiving HAART who first initiated antiretroviral therapy within the last 6 months of Day 1 Patients receiving HAART who have changed their antiretroviral regimen due to safety or efficacy associated to HIV treatment within the last 3 months prior to Day 1. However, if changes are required to a patient's HAART regimen to meet the requirements of the protocol, these changes are allowed at the screening visit. The patient should wait a minimum of 1 month prior to Day 1 after a repeat of HIV viral load has been confirmed, <40 copies/ mL Use of prohibited HAART regimens within 1 month of Day 1 and throughout the treatment period of the trial (patients receiving HAART who have changed their antiretroviral regimen to initiate any HCV treatment within 6 weeks prior to Day 1) Laboratory values: Neutrophil count <1500 cells/μL (<1200 cells/ μL for Blacks) Platelet count <90,000 cells/μL Hemoglobin ≤12 g/dL for females, hemoglobin ≤13 g/dL for males Total bilirubin ≥34 μmol/L (or ≥2 mg/dL) unless a patient has a documented history of Gilbert's disease or antiretroviral regimen contains atazanavir Alanine aminotransferase ≥5*upper limit of normal

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daclatsvir + Ribavirin + PEG-Interferon alfa-2a<br> | Drug: Daclatasvir<br>* Tablets; oral; 30, 60, or 90 mg; once daily; up to 24 weeks<br>* Other names: BMS-790052;Drug: Ribavirin<br>* Tablets; oral; for patients weighing <75 kg, the total dose is 1000 mg per day (2 200-mg tablets in the morning and 3 200-mg tablets in the evening); for patients weighing >75 kg, the total dose is 1200 mg per day (3 200-mg tablets in morning and 3 200-mg tablets in evening); twice daily with food; 24 or 48 weeks depending on response<br>* Other names: Copegus®;Drug: PEG-Interferon alfa 2a<br>* Syringe, subcutaneous injection, 180 μg, once weekly, 24 or 48 weeks depending on response<br>* Other names: Pegylated interferon;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) | SVR12 was defined as hepatitis C virus (HCV) values lower than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy. SVR12 was defined as hepatitis C virus (HCV) values lower than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy. | Follow-up Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) | Participants who achieved HCV RNA levels lower than the LLOQ i.e., 25 IU/ml, TD or TND. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy. | Week 1, 2, 4, 6, 8, 12 and at both Weeks 4 and 12; end of treatment; and follow-up Weeks 12 and 24 | 
| Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Participants who achieved HCV RNA levels lower than the LLOQ, TND. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy. | Week 1, 2, 4, 6, 8, and 12 and at both Weeks 4 and 12; end of treatment; and follow-up Weeks 12 and 24 | 
| Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL | Participants who received HAART, maintained HIV RNA <40 copies/mL, and experienced confirmed HIV RNA ≥ 400 copies/mL were determined. | End of treatment (up to Week 48) | 
| Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene | Percentages calculated as number of responders/number who received treatment. | Follow-up Week 12 | 
| Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation | Adverse event was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not necessarily have 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-threating, an important medical event, or a congenital anomaly/birth defect; or required prolonged hospitalization. HAART=highly active antiretroviral therapy. | From Day 1 to 7 days post last dose of study treatment (up to Week 48) |