Study of the Anti-HCV Drug (BMS-790052) Combined With Peginterferon and Ribavirin in Patients Who Failed Prior Treatment

Study Overview
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Brief Summary
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The purpose of this study is to determine whether BMS-790052 added to Peginterferon Alfa-2a and ribavirin can result in higher cure rates in patients who previously failed therapy and may have limited response to retreatment with Peginterferon Alfa-2a and ribavirin alone.

Official Title
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A Phase 2B Study of BMS-790052 in Combination With Peginterferon Alfa-2a and Ribavirin in Chronic Hepatitis C Genotype 1 Infected Subjects Who Are Null or Partial Responders to Prior Treatment With Peginterferon Alfa Plus Ribavirin Therapy

Conditions
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Hepatitis C Virus

Intervention / Treatment
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* Drug: BMS-790052
* Drug: BMS-790052
* Drug: Placebo
* Drug: peginterferon alfa-2a
* Drug: ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects chronically infected with HCV genotype 1 Non-responder to prior therapy with peginterferon alfa and ribavirin HCV RNA viral load of 100,00 IU/mL Results of a liver biopsy ≤ 24 months prior to randomization consistent with chronic HCV infection; for compensated cirrhotics can be any time prior to randomization (compensated cirrhotics biopsy enrollment will be capped at 25% of randomized study population) Ultrasound, CT scan or MRI results 12 months prior to randomization that do not demonstrate hepatocellular carcinoma Body Mass Index (BMI) of 18 to 35 kg/m2 Exclusion Criteria: Positive for Hepatitis B infection (HBsAg) or HIV-1/HIV-2 antibody at screening Evidence of medical condition associated with chronic liver disease other than HCV Evidence of decompensated cirrhosis based on radiologic criteria or biopsy

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: BMS-790052 plus peginterferon alfa-2a and ribavirin<br>(prior null responders) | Drug: BMS-790052<br>* Film coated tablet, Oral, 20 mg, once daily, 24 weeks<br>Drug: peginterferon alfa-2a<br>* Solution for injection, Subcutaneous injection, 180 µg, weekly, 24 or 48 weeks<br>* Other names: Pegasys®;Drug: ribavirin<br>* Film coated tablet, Oral, 1,000 or 1,200 mg based on weight, divided dose taken twice a day (BID), 48 weeks<br>* Other names: Copegus®;|
| Experimental: Arm 2: BMS-790052 plus peginterferon alfa-2a and ribavirin<br>(prior null responders) | Drug: BMS-790052<br>* Film coated Tablet, Oral, 60 mg, once daily (divided dose taken BID), 48 weeks<br>Drug: peginterferon alfa-2a<br>* Solution for injection, Subcutaneous injection, 180 µg, weekly, 24 or 48 weeks<br>* Other names: Pegasys®;Drug: ribavirin<br>* Film coated tablet, Oral, 1,000 or 1,200 mg based on weight, divided dose taken twice a day (BID), 48 weeks<br>* Other names: Copegus®;|
| Experimental: Arm 3: BMS-790052 plus peginterferon alfa-2a and ribavirin<br>(prior partial responders) | Drug: BMS-790052<br>* Film coated tablet, Oral, 20 mg, once daily, 24 weeks<br>Drug: peginterferon alfa-2a<br>* Solution for injection, Subcutaneous injection, 180 µg, weekly, 24 or 48 weeks<br>* Other names: Pegasys®;Drug: ribavirin<br>* Film coated tablet, Oral, 1,000 or 1,200 mg based on weight, divided dose taken twice a day (BID), 48 weeks<br>* Other names: Copegus®;|
| Experimental: Arm 4: BMS-790052 plus peginterferon alfa-2a and ribavirin<br>(prior partial responders) | Drug: BMS-790052<br>* Film coated Tablet, Oral, 60 mg, once daily (divided dose taken BID), 48 weeks<br>Drug: peginterferon alfa-2a<br>* Solution for injection, Subcutaneous injection, 180 µg, weekly, 24 or 48 weeks<br>* Other names: Pegasys®;Drug: ribavirin<br>* Film coated tablet, Oral, 1,000 or 1,200 mg based on weight, divided dose taken twice a day (BID), 48 weeks<br>* Other names: Copegus®;|
| Experimental: Arm 5: Placebo plus peginterferon alfa-2a and ribavirin<br>(prior partial responders only) | Drug: Placebo<br>* Film coated tablet, Oral, 0mg, Once daily, 24 weeks<br>Drug: peginterferon alfa-2a<br>* Solution for injection, Subcutaneous injection, 180 µg, weekly, 24 or 48 weeks<br>* Other names: Pegasys®;Drug: ribavirin<br>* Film coated tablet, Oral, 1,000 or 1,200 mg based on weight, divided dose taken twice a day (BID), 48 weeks<br>* Other names: Copegus®;|

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 RNA at both Weeks 4 and 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. | Week 4, Week 12 | 
| Percentage of Participants With 24-week Sustained Virologic Response (SVR24) | SVR24 was defined as undetectable RNA (Hepatitis C Virus [HCV] RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at follow-up Week 24. TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. | Follow-up Week 24 | 
| Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs) and Who Died On-treatment | 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. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity; or was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. | From first dose to last dose plus 7 days, up to 49 weeks | 
| Number of Participants With Serious Adverse Events (SAEs) and Who Died During Follow-up Period | 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. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. | From day 8 post last dose of treatment up-to Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Rapid Virologic Response (RVR) | RVR was defined as undetectable RNA ie., Hepatitis C virus (HCV) RNA <lower limit of quantitation [LLOQ], target not detected (TND) at Week 4. TND was 10 IU/mL. HCV RNA levels were measured by the Roche Cobas® TaqMan® HCV Test version 2.0 from the central laboratory. | Week 4 | 
| Percentage of Participants With Complete Early Virologic Response (cEVR) | cEVR was defined as undetectable RNA ie., Hepatitis C virus (HCV) RNA <lower limit of quantitation [LLOQ], target not detected (TND) at Week 12. TND was 10 IU/mL. HCV RNA levels were measured by the Roche Cobas® TaqMan® HCV Test version 2.0 from the central laboratory. | Week 12 | 
| Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) | SVR12 was defined as undetectable RNA ie., Hepatitis C virus (HCV) RNA <lower limit of quantitation (LLOQ), target not detected (TND) at follow-up Week 12. TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. | Follow-up Week 12 | 
| Number of Participants With Genotypic-1A Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures | Non-structural protein 5A of HCV resistance associated polymorphism in GT-1a samples included M28L/T/V, Q30H, L31M, H54Y, H58C/D/N/P/Q, E62D and Y93C. | Baseline to follow-up Week 48 | 
| Number of Participants With Genotypic-1B Substitution at Baseline, On-treatment and During Follow-up Associated With Virologic Failures | Non-structural protein 5A of HCV resistance associated polymorphisms in GT-1b samples, included L28M/V, R30H/Q, L31M, Q54H/N/Y, P58A/Q/S, Q62E/K/N/R/S, A92T/V and Y93F/H. | Baseline to follow-up Week 48 |