Phase III China GT 1b Interferon (IFN) Intolerant Prev Exclude Dual

Study Overview
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Brief Summary
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Patients with chronic hepatitis genotype 1b, who are intolerant or ineligible to Interferon alfa therapy with or without Ribavirin, will be treated for 24 weeks with Daclatasvir (DCV) Dual regimen (= Daclatasvir + Asunaprevir) and followed for an additional 24 weeks post-treatment in order to determine the safety and efficacy of the DCV DUAL regimen

Official Title
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A Phase 3, Open-Label Study With Daclatasvir And Asunaprevir (DUAL) for Subjects With Genotype 1b Chronic Hepatitis C (HCV) Infection Who Are Intolerant or Ineligible to Interferon Alfa Therapies With or Without Ribavirin

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Asunaprevir
* Drug: Daclatasvir


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Males and females, ≥ 18 years of age Subjects chronically infected with HCV Genotype (GT)-1b only as documented by positive HCV RNA and anti-HCV antibody at screening and either: Positive anti-HCV antibody, HCV RNA or positive HCV genotype test at least 6 months prior to screening or Liver biopsy consistent with chronic HCV infection (evidence of fibrosis and/or inflammation) Subjects who are intolerant to previous therapy with Interferon Alfa (IFNα) either with or without Ribavirin (RBV) (I±R)(independent of previous response to therapy) or ineligible for I±R and who meet one of the criteria below: Anemia: the I±R intolerants are subjects who were previously treated with IFNα/RBV therapy and had a decline in hemoglobin to < 8.5 g/dL during therapy (documented); the I±R ineligibles are subjects who have a screening hemoglobin < 10.0 g/dL and ≥ 8.5 g/dL OR Neutropenia: the I±R intolerants are subjects who were previously treated with IFNα/RBV therapy and had a decline in absolute neutrophil count (ANC) to < 0.5 x 10(9) during therapy (documented); the I±R ineligibles are subjects who have a screening ANC < 1.5 x 10(9) cells/L and ≥ 0.5 x 10(9) cells/L OR Thrombocytopenia: the I±R intolerants are subjects who were previously treated with IFNα/RBV therapy and had a decline in platelet counts < 25,000 cells/mm3 during therapy (documented); the I±R ineligibles are subjects who have a screening platelet count of < 90 x 10(9) cells/L and ≥ 50 x 10(9) cells/L HCV RNA ≥ 10,000 IU/mL Seronegative for Human Immunodeficiency Virus (HIV) and hepatitis B surface antigen (HBsAg) Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive. BMI = weight (kg)/ [height(m)]2 at screening Subjects with compensated cirrhosis are permitted (compensated cirrhotics are capped at approximately 40%). If a subject does not have cirrhosis, a liver biopsy within three years prior to enrollment is required to demonstrate the absence of cirrhosis. If cirrhosis is present, any prior liver biopsy is sufficient. For countries where liver biopsy is not required prior to treatment and where noninvasive imaging tests (Fibroscan® ultrasound) are approved for staging of liver disease, non-invasive imaging test results may be used to assess the extent of liver disease Exclusion Criteria: Prior treatment with HCV direct acting antiviral (DAA) Evidence of a medical condition contributing to chronic liver disease other than HCV Evidence of decompensated liver disease including, but not limited to, a history or presence of ascites, bleeding varices, or hepatic encephalopathy Diagnosed or suspected hepatocellular carcinoma or other malignancies Uncontrolled diabetes or hypertension History of moderate to severe depression. Well-controlled mild depression is allowed Total bilirubin ≥ 34 µmol/L (or ≥ 2 mg/dL) unless subject has a documented history of Gilbert's disease Confirmed alanine aminotransferase (ALT) ≥ 5 x upper limit of normal (ULN) Confirmed albumin < 3.5 g/dL (35 g/L) Alpha-fetoprotein (AFP) > 100 ng/mL OR ≥ 50 and ≤ 100 ng/mL requires a liver ultrasound and subjects with findings suspicious of hepatocellular carcinoma (HCC) are excluded Confirmed hemoglobin < 8.5 g/dL Confirmed ANC < 0.5 x 10(9) cells/L Confirmed platelet count < 50,000 cells/mm3

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Asunaprevir + Daclatasvir<br>Asunaprevir 100mg soft capsule by mouth twice daily for 24 weeks and Daclatasvir 60mg tablet by mouth once daily for 24 weeks | Drug: Asunaprevir<br> <br> * Other names: BMS-650032;Drug: Daclatasvir<br> <br> * Other names: BMS-790052;|

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 (SVR) at Post-Treatment Follow-up Week 24 (SVR24) | SVR was defined as Hepatitis C Virus ribonucleic acid (HCV RNA) < lower limit of quantitation (LLOQ) target detected (TD) or not detected (TND) at post-treatment follow-up Week 24. | 24 Weeks after treatment discontinuation (Follow-up Week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response (SVR) at Post-Treatment Follow-up Week 12 (SVR12) | SVR12 was defined as HCV RNA < LLOQ target detected or not detected at post-treatment follow-up Week 12. For SVR12, missing HCV RNA data at follow-up Week 12 was imputed using the Next Value Carried Backwards (NVCB) approach. | 12 Weeks after treatment discontinuation (Follow-up Week 12) | 
| Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Death, and AEs Leading to Discontinuation | An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, or a congenital anomaly, or a medically important event. | 7 days after treatment discontinuation | 
| Percentage of Participants With SVR24 by the rs12979860 Single Nucleotide Polymorphisms (SNP) in the IL 28B Gene at Post-Treatment Follow-up Week 24 | Participants categorized into three genotypes based on SNPs in the IL28B gene were assessed for SVR24, defined as response in which hepatitis C virus RNA levels below lower limit of quantitation or below target detected or target not detected at follow-up Week 24. | 24 Weeks after treatment discontinuation (Follow-up Week 24) | 
| Percentage of Participants With HCV RNA< LLOQ Target Not Detected at the End of Treatment (Week 24) | Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® Taqman quantitative RT-PCR assay, v2.0. The lower and upper limits of quantitation (LOQs) of the assay for HCV GT-1 were 25 IU/mL and 3.91 X10^8 IU/mL, respectively; the limit of detection was   10 IU/mL | Week 24 (End-of Treatment) | 
| Number of Participants With Rapid Virologic Response (RVR) | RVR was defined as HCV RNA < LLOQ, target not detected at treatment Week 4. | Treatment Week 4 | 
| Percentage of Participants With Complete Early Virologic Response (cEVR) | cEVR was defined as HCV RNA < LLOQ, target not detected at treatment Week 12. | Treatment Week 12 | 
| Number of Participants With Extended Rapid Virologic Response (eRVR) | eRVR was defined as HCV RNA < LLOQ, target not detected at treatment Weeks 4 and 12. | Treatment Week 4 and Week 12 | 
| Number of Participants With HCV RNA < LLOQ Target Detected or Not Detected at the End of Treatment (Week 24) | Antiviral efficacy is measured by the number of participants with HCV RNA< LLOQ (lower limit of quantification), TD (target detected) or TND (target not detected) at End of Treatment (Week 24) | Week 24 (End-of Treatment) | 
| Number of Participants With Virologic Response (VR) at Treatment Week 4 and 12 | VR was defined as HCV RNA < LLOQ, target detected or not detected at specific time points (Week 4 and Week 12) | Treatment Week 4 and 12 |