Study in Genotype 2 or 3 Patients With Chronic Hepatitis Virus Infection

Study Overview
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Brief Summary
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To identify a shorter duration of antiviral therapy (12 or 16 weeks) for the combination of daclatasvir with pegylated interferon alfa-2a and ribavirin.

Official Title
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A Phase 2B Pilot Study of Short-Term Treatment of BMS-790052 in Combination With Peg-Interferon Alfa-2a and Ribavirin in Treatment Naive Subjects With Chronic Hepatitis C Genotype 2 or 3 Infection

Conditions
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Hepatitis C Virus

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participants chronically infected with hepatitis C virus (HCV) genotype 2 or 3 No previous exposure to an interferon formulation (ie, interferon alfa, pegylated interferon alfa-2a ) or ribavirin Body mass index (BMI) of 18 to 35 kg/m^2, inclusive. BMI=weight (kg)/height (m)^2 Males and females, 18 - 70 years of age Key Exclusion Criteria: Liver transplant recipients Documented or suspected hepatocellular carcinoma Evidence of decompensated cirrhosis History of chronic hepatitis B virus (HBV). Patients with resolved HBV infection may participate Current or known history of cancer Any gastrointestinal disease or surgical procedure that may impact the absorption of study drug Inability to tolerate oral medication Poor venous access Severe psychiatric disease History of chronic pulmonary disease History of cardiomyopathy, coronary artery disease (including angina), interventive procedure for coronary artery disease (including angioplasty, stent procedure, or cardiac bypass surgery), ventricular arrhythmia,, or other clinically significant cardiac disease History of or current electrocardiogram findings indicative of cardiovascular instability Preexisting ophthalmologic disorders considered clinically significant on eye History of uncontrolled diabetes mellitus Any known contraindication to pegylated interferon alfa-2a or ribavirin not otherwise specified. Positive hepatitis B virus surface antigen, HIV-1 or HIV-2 Ab Prior exposure to any HCV direct antiviral agent (eg, HCV protease, polymerase, previous nonstructural protein 5A inhibitors) Exposure to any investigational drug or placebo

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 |
| --- | --- |
| Active Comparator: Control<br>Placebo + Pegylated interferon alfa-2a + Ribavirin | Drug: Placebo<br>* Tablets, oral, 0 mg, once daily, for 24 weeks<br>Drug: Pegylated interferon alfa-2a<br>* Solution for injection, subcutaneous injection, 180 µg/0.5 mL, once weekly, for 12, 16, or 24 weeks<br>* Other names: Pegasys®;Drug: Ribavirin<br>* Tablets, oral, 800 mg, twice daily, for 12, 16, or 24 weeks<br>* Other names: Copegus®;|
| Experimental: 12 Week Cohort<br>Daclatasvir + Pegylated interferon alfa-2a + Ribavirin | Drug: Daclatasvir<br>* Tablets, oral, 60 mg, once daily, for 12, 16, or 24 weeks<br>* Other names: BMS-790052;Drug: Pegylated interferon alfa-2a<br>* Solution for injection, subcutaneous injection, 180 µg/0.5 mL, once weekly, for 12, 16, or 24 weeks<br>* Other names: Pegasys®;Drug: Ribavirin<br>* Tablets, oral, 800 mg, twice daily, for 12, 16, or 24 weeks<br>* Other names: Copegus®;|
| Experimental: 16 Week Cohort<br>Daclatasvir + Pegylated interferon alfa-2a + Ribavirin | Drug: Daclatasvir<br>* Tablets, oral, 60 mg, once daily, for 12, 16, or 24 weeks<br>* Other names: BMS-790052;Drug: Pegylated interferon alfa-2a<br>* Solution for injection, subcutaneous injection, 180 µg/0.5 mL, once weekly, for 12, 16, or 24 weeks<br>* Other names: Pegasys®;Drug: Ribavirin<br>* Tablets, oral, 800 mg, twice daily, for 12, 16, or 24 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 Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 2 | SVR24 was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at follow-up Week 24. The LLOQ was 25 IU/mL, and <LLOQ, 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 | 
| Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 24 (SVR24) for Hepatitis C Virus (HCV) Genotype 3 | SVR24 was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at follow-up Week 24. The LLOQ was 25 IU/mL, and <LLOQ, 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 2 | RVR was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at Week 4. The LLOQ was 25 IU/mL, and <LLOQ, 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 Achieving Rapid Virologic Response (RVR) at Week 4 for Hepatitis C Virus (HCV) Genotype 3 | RVR was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at Week 4. The LLOQ was 25 IU/mL, and <LLOQ, 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 Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 2 | cEVR was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at Week 12. The LLOQ was 25 IU/mL, and <LLOQ, 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 Achieving Complete Early Virologic Response (cEVR) at Week 12 for Hepatitis C Virus (HCV) Genotype 3 | cEVR was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at Week 12. The LLOQ was 25 IU/mL, and <LLOQ, 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 Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 2 | SVR12 was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at follow-up Week 12. The LLOQ was 25 IU/mL, and <LLOQ, 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 | 
| Percentage of Participants Achieving Sustained Virologic Response at Follow-up Week 12 (SVR12) for Hepatitis C Virus (HCV) Genotype 3 | SVR12 was defined as undetectable HCV RNA (HCV RNA <lower limit of quantitation [LLOQ], target not detected [TND]) at follow-up Week 12. The LLOQ was 25 IU/mL, and <LLOQ, 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 Virologic Failure for Hepatitis C Virus (HCV) Genotype 2 | Virologic failure was defined as: Virologic breakthrough: confirmed >1 log10 increase in HCV RNA over nadir or confirmed RNA ≥lower limit of quantitation (LLOQ) after confirmed HCV RNA <LLOQ, target not detected (TND) while on treatment <1 log10 decrease in HCV RNA from baseline at Week 4 of treatment Failure to achieve early virologic response: <2 log10 decrease in HCV RNA from baseline and HCV RNA ≥LLOQ at Week 12 of treatment HCV RNA ≥LLOQ or <LLOQ, target detected (TD) at the end of treatment (EOT) (including early discontinuation) Relapse, defined as HCV RNA ≥LLOQ or <LLOQ, TD during follow-up, after HCV RNA <LLOQ, TND at EOT. The LLOQ was 25 IU/mL, and <LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. | Baseline up to Week 48 | 
| Number of Participants With Virologic Failure for Hepatitis C Virus (HCV) Genotype 3 | Virologic failure was defined as: Virologic breakthrough: confirmed >1 log10 increase in HCV RNA over nadir or confirmed RNA ≥lower limit of quantitation (LLOQ) after confirmed HCV RNA <LLOQ, target not detected (TND) while on treatment <1 log10 decrease in HCV RNA from baseline at Week 4 of treatment Failure to achieve early virologic response: <2 log10 decrease in HCV RNA from baseline and HCV RNA ≥LLOQ at Week 12 of treatment HCV RNA ≥LLOQ or <LLOQ, target detected (TD) at the end of treatment (EOT) (including early discontinuation) Relapse, defined as HCV RNA ≥LLOQ or <LLOQ, TD during follow-up, after HCV RNA <LLOQ, TND at EOT. The LLOQ was 25 IU/mL, and <LLOQ, TND was 10 IU/mL. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. | Baseline up to Week 48 | 
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs, and Treatment-related AEs and Who Died During Treatment Period | AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not has 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. Treatment-related AE was defined as an AE that had certain, probable, possible, or unknown relationship to study drug. Mild (Grade 1): awareness of event but easily tolerated; Moderate (Grade 2): discomfort enough to cause some interference with usual activity; Severe (Grade 3): inability to carry out usual activity; Very severe (Grade 4): debilitating, significantly incapacitates participant despite symptomatic therapy. Only Grade 2-4 treatment-related AEs were reported. | Baseline (Day 1) up to 24 weeks (treatment period) | 
| Number of Participants With Adverse Events (AEs), 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 has 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. | From end of treatment period up to Week 48 (follow-up period) |