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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Hepatitis C Infection

Intervention / Treatment
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* Drug: BMS-790052
* Drug: BMS-790052
* Drug: Placebo
* Drug: Peginterferon alfa-2b
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (BMS-790052, plus Peginterferon alfa-2b, Ribavirin)<br>Treatment Naive | Drug: BMS-790052<br>* Tablets, Oral, 10 mg, daily, 24-48 weeks<br>Drug: Peginterferon alfa-2b<br>* Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks<br>* Other names: PegIntron®;Drug: Ribavirin<br>* Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks<br>* Other names: Rebetol®;|
| Experimental: Arm B (BMS-790052, plus Peginterferon alfa-2b, Ribavirin)<br>Treatment Naive | Drug: BMS-790052<br>* Tablets, Oral, 60 mg, daily, 24-48 weeks<br>Drug: Peginterferon alfa-2b<br>* Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks<br>* Other names: PegIntron®;Drug: Ribavirin<br>* Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks<br>* Other names: Rebetol®;|
| Placebo Comparator: Arm C (Placebo, plus Peginterferon alfa-2b, Ribavirin)<br>Treatment Naive | Drug: Placebo<br>* Tablets, Oral, 0 mg, daily, 48 weeks<br>Drug: Peginterferon alfa-2b<br>* Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks<br>* Other names: PegIntron®;Drug: Ribavirin<br>* Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks<br>* Other names: Rebetol®;|
| Experimental: Arm D (BMS-790052, plus peginterferon alfa-2b, Ribavirin)<br>Non-Responder | Drug: BMS-790052<br>* Tablets, Oral, 10 mg, daily, 24-48 weeks<br>Drug: Peginterferon alfa-2b<br>* Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks<br>* Other names: PegIntron®;Drug: Ribavirin<br>* Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks<br>* Other names: Rebetol®;|
| Experimental: Arm E (BMS-790052, plus Peginterferon alfa-2b, Ribavirin)<br>Non-Responder | Drug: BMS-790052<br>* Tablets, Oral, 60 mg, daily, 24-48 weeks<br>Drug: Peginterferon alfa-2b<br>* Syringe, Subcutaneous, 180µg, weekly, 24-48 weeks<br>* Other names: PegIntron®;Drug: Ribavirin<br>* Capsules, Oral, 600 to 1000 mg based on weight, daily, 24-48 weeks<br>* Other names: Rebetol®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Extended Rapid Virologic Response (eRVR) | 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. | At Weeks 4 and 12 on treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Rapid Virologic Response (RVR) | 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 . | At Week 4 on treatment | 
| Percentage of Participants With Complete Early Virologic Response (cEVR) | 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 | At Week 12 on treatment | 
| Percentage of Participants With a Sustained Virologic Response (SVR) at Weeks 4, 12, and 24 | 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 . | Follow-up Weeks 4, 12, and 24 | 
| Percentage of Participants With Virologic Failure | 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. | From on-treatment Week 1 to Follow-up Week 24 |