Study of pegInterferon Alfa-2a, Ribavirin, and Daclatasvir (BMS-790052) With or Without BMS-650032 for Participants in Some Hepatitis C Virus Trials

Study Overview
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Brief Summary
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The purpose of this study is to provide anti-hepatitis C virus drugs to patients who received placebo + peginterferon alfa-2a + ribavirin in prior Bristol-Myers Squibb (BMS) studies and determine whether addition of these drugs results in higher cure rates in patients who previously failed therapy. Approximately 100 genotype 1b patients who received placebo in BMS study NCT01428063 (AI447-028) will receive active drugs in this study.

Detailed Description
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Intervention Model: Parallel: for all patients entering the trial Cross-over: for genotype 1b patients rolling over from NCT01428063 (AI447-028) who require rescue therapy after initial treatment in this study Peginterferon alfa-2a Ribavirin Daclatasvir Asunaprevir

Official Title
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An Open-Label Re-Treatment Study With PegInterferon Alfa-2a, Ribavirin and BMS-790052 With or Without BMS-650032 for Subjects With Chronic Hepatitis C

Conditions
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Hepatitis C Virus Infection

Intervention / Treatment
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* Drug: Daclatasvir
* Drug: Asunaprevir
* Drug: Pegylated interferon alfa-2a
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Prior participation in any BMS-790052, BMS-650032, or BMS-791325 trial and assigned to control arm (pegIFNα-2a/ribavirin + placebo) during the trial Hepatitis C virus (HCV) genotype 1, 2, 3, or 4 (mixed genotypes are not permitted) HCV RNA viral load detectable Key Exclusion Criteria: Discontinuation from a prior BMS HCV clinical trial due to a pegIFNα-2a/ribavirin-related event Any anti-HCV therapy following initial treatment with BMS-650032, BMS-790052, or BMS-791325 Positive for hepatitis B infection (hepatitis B surface antigen) or HIV-1 or HIV-2 antibody at screening Evidence of medical condition associated with chronic liver disease other than HCV infection Evidence of decompensated cirrhosis based on radiologic criteria or biopsy

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daclatasvir + Asunaprevir + PegIFNα-2a + Ribavirin<br>Patients received daclatasvir, 60-mg tablet, by mouth once daily + asunaprevir, 100-mg capsule or 200-mg tablet, by mouth twice daily + pegIFNα-2a, 180-μg solution, subcutaneously weekly + ribavirin, weight-based dosing (<75 kg=1000 mg once daily; >=75 kg=1200 mg once daily) for 24 weeks | Drug: Daclatasvir<br> <br> * Other names: BMS-790052;Drug: Asunaprevir<br> <br> * Other names: BMS-650032;Drug: Pegylated interferon alfa-2a<br> <br> * Other names: pegIFNα-2a, Pegasys®;Drug: Ribavirin<br> <br> * Other names: Copegus®;|
| Experimental: Daclatasvir + PegIFNα-2a + Ribavirin<br>Patients received daclatasvir, (two 30-mg tablets or one 60-mg tablet, by mouth once daily) + pegIFNα-2a, 180-μg solution, subcutaneously weekly + ribavirin, weight-based dosing (<75 kg=1000 mg once daily; >=75 kg=1200 mg once daily) for 24 weeks | Drug: Daclatasvir<br> <br> * Other names: BMS-790052;Drug: Pegylated interferon alfa-2a<br> <br> * Other names: pegIFNα-2a, Pegasys®;Drug: Ribavirin<br> <br> * Other names: Copegus®;|
| Experimental: Daclatasvir + Asunaprevir<br>Patients received daclatasvir, 60-mg tablet, by mouth once daily + asunaprevir, 100-mg capsule, by mouth twice daily for 24 weeks | Drug: Daclatasvir<br> <br> * Other names: BMS-790052;Drug: Asunaprevir<br> <br> * Other names: BMS-650032;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) for All Nonresponders With Genotype 1 Hepatitis C Virus (HCV) | SVR12 defined as HCV RNA<limit of quantitation at follow-up Week 12. Nonresponder (NR)=prior NR to pegIFN-2a or ribavirin. | Week 12 (Follow-up period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Other Than Genotype 1 With Sustained Virologic Response at Post Treatment Week 12 (SVR12) | SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. | Week 12 (Follow-up period) | 
| Percentage of Participants With Rapid Virologic Response (RVR) at Post Treatment Week 4 | RVR was defined as the percentage of participants with hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target not detected at Week 4. | Week 4 | 
| Percentage of Participants With Extended Rapid Virologic Response (eRVR) | eRVR was defined as the percentage of participants with hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target not detected at both weeks 4 and 12. | Week 4 and 12 | 
| Percentage of Participants With Complete Early Virologic Response (cEVR) | cEVR was defined as the percentage of participants with hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target not detected at week 12. | Week 12 | 
| Percentage of Participants With End of the Treatment Response (EOTR) | EOTR was defined as the percentage of participants with hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target not detected at end of treatment. | End of the study (Week 24) | 
| Percentage of Participants With Sustained Virologic Response at Post Treatment Week 24 (SVR24) | SVR24 was defined as the percentage of participants with hepatitis C virus (HCV) RNA less than the lower limit of quantitation, target detected or target not detected at follow-up week 24. | Week 24 (Follow-up) | 
| Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Who Died During the Study | AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting 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-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. | For AEs: Day 1 until last visit. For SAEs: Day 1 until 30 days post discontinuation of dosing or participation |