Phase 2b Study of BMS-986094 and Daclatasvir, With or Without Ribavirin for the Treatment of Patients With Chronic Hepatitis C

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness of BMS-986094 and Daclatasvir (DCV) when given in combination with or without Ribavirin

Official Title
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Phase 2b Evaluation of PegIFNα Free Combinations of BMS-986094 (INX-08189) and Daclatasvir, With or Without Ribavirin, in Treatment Naive and Treatment Experienced Patients With Chronic Hepatitis C

Conditions
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Hepatitis C Virus

Intervention / Treatment
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* Drug: Daclatasvir
* Drug: Daclatasvir
* Drug: BMS-986094
* Drug: BMS-986094
* Drug: BMS-986094
* Drug: Ribavirin
* Drug: Placebo for BMS-986094


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, ≥ 18 years of age Subjects chronically infected with Hepatitis C virus (HCV) genotype 1,2,3 or 4 HCV RNA viral load ≥ 10,000 IU/mL Subjects with compensated cirrhosis are permitted (compensated cirrhotics are capped at approximately 25% of treated population) Body Mass Index (BMI) of 18 to 35 kg/m2 Seronegative for Hepatitis C virus (HIV) and Hepatitis B Exclusion Criteria: Evidence of decompensated liver disease Evidence of medical condition contributing to chronic liver disease other than HCV

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Daclasasvir + BMS-986094 (100 mg) + Placebo<br>Subjects will be re-randomized at Week 12 to complete therapy at this visit and enter post-treatment follow-up, or continue therapy for an additional 12 weeks (24 weeks of therapy) Re-Randomized Arm 1 to Arm 1a and 1b (additional 12 weeks treatment) | Drug: Daclatasvir<br>* Film coated tablet, Oral, 60 mg, Once daily, 12 or 24 weeks<br>* Other names: BMS-790052 (DCV);Drug: BMS-986094<br>* Capsule, Oral, 100 mg, Once daily, 12 or 24 weeks<br>Drug: Placebo for BMS-986094<br>* Capsule, Oral, 0 mg, Once daily, 12 or 24 weeks<br>|
| Experimental: Arm 2: Daclasasvir + BMS-986094 (200 mg)<br>Subjects will be re-randomized at Week 12 to complete therapy at this visit and enter post-treatment follow-up, or continue therapy for an additional 12 weeks (24 weeks of therapy) Re-Randomized Arm 2 to Arm 2a and 2b (additional 12 weeks treatment) | Drug: Daclatasvir<br>* Film coated tablet, Oral, 60 mg, Once daily, 12 or 24 weeks<br>* Other names: BMS-790052 (DCV);Drug: BMS-986094<br>* Capsule, Oral, 200 mg, Once daily, 12 or 24 weeks<br>|
| Experimental: Arm 3: Daclasasvir + BMS-986094 (100 mg) + Placebo + Ribavirin<br>Subjects will be re-randomized at Week 12 to complete therapy at this visit and enter post-treatment follow-up, or continue therapy for an additional 12 weeks (24 weeks of therapy) Re-Randomized Arm 3 to Arm 3a and 3b (additional 12 weeks treatment) | Drug: Daclatasvir<br>* Film coated tablet, Oral, 60 mg, Once daily, 12 or 24 weeks<br>* Other names: BMS-790052 (DCV);Drug: BMS-986094<br>* Capsule, Oral, 100 mg, Once daily, 12 or 24 weeks<br>Drug: Ribavirin<br>* Film coated tablet, Oral, 1000 mg or 1200 mg based on weight, Twice daily, 12 or 24 weeks<br>* Other names: Copegus®;Drug: Placebo for BMS-986094<br>* Capsule, Oral, 0 mg, Once daily, 12 or 24 weeks<br>|
| Experimental: Arm 4: Daclasasvir + BMS-986094 (200 mg) + Ribavirin<br>Subjects will be re-randomized at Week 12 to complete therapy at this visit and enter post-treatment follow-up, or continue therapy for an additional 12 weeks (24 weeks of therapy) Re-Randomized Arm 4 to Arm 4a and 4b (additional 12 weeks treatment) | Drug: Daclatasvir<br>* Film coated tablet, Oral, 60 mg, Once daily, 12 or 24 weeks<br>* Other names: BMS-790052 (DCV);Drug: BMS-986094<br>* Capsule, Oral, 200 mg, Once daily, 12 or 24 weeks<br>Drug: Ribavirin<br>* Film coated tablet, Oral, 1000 mg or 1200 mg based on weight, Twice daily, 12 or 24 weeks<br>* Other names: Copegus®;|
| Experimental: Arm 5: Daclasasvir + BMS-986094 (200 mg)<br>Genotype 1 PI-failure subjects | Drug: Daclatasvir<br>* Film coated tablet, Oral, 60 mg, Once daily, 24 weeks<br>* Other names: BMS-790052 (DCV);Drug: BMS-986094<br>* Capsule, Oral, 200 mg, Once daily, 24 Weeks<br>|
| Experimental: Arm 6: Daclasasvir + BMS-986094 (200 mg)<br>Genotype 4 naive subjects | Drug: Daclatasvir<br>* Film coated tablet, Oral, 60 mg, Once daily, 24 weeks<br>* Other names: BMS-790052 (DCV);Drug: BMS-986094<br>* Capsule, Oral, 200 mg, Once daily, 24 Weeks<br>|
| Experimental: Arm 7: Daclasasvir + BMS-986094 (200 mg)<br>Genotype 2/3 NR/relapse Subjects | Drug: Daclatasvir<br>* Film coated tablet, Oral, 60 mg, Once daily, 24 weeks<br>* Other names: BMS-790052 (DCV);Drug: BMS-986094<br>* Capsule, Oral, 200 mg, Once daily, 24 Weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with SVR4 defined as HCV RNA < LOQ (25 IU/mL; detectable or undetectable) at 4 weeks post treatment to be evaluated in GT1 (naive and NR) subjects randomized to the 12-week treatment arm (arms 1a, 2a, 3a, 4a) | SVR = Sustained virologic response HCV = Hepatitis C virus RNA = Ribonucleic acid LOQ = Limit of quantitation | Follow up Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of treated subjects with SVR4 in genotype (GT) 1 naive and non-responder (NR) subjects randomized to the 24-week treatment arms (arms 1b, 2b, 3b, 4b) |  | Follow up Week 4 (SVR4) | 
| Proportion of treated subjects with SVR4 in genotype 1 protease inhibitor (PI)failures, genotype 4 naive, and genotype 2/3 NR/relapse subjects (arms 5, 6, 7) |  | Follow up Week 4 (SVR4) | 
| Proportion of treated subjects in each study population (GT1 naive, GT1 NR, or GT1 PI-failure, GT4 naive, GT2/3 NR/relapse), for each regimen and duration, who achieve HCV RNA < LOQ at post-treatment |  | Post-treatment Week 2 (SVR2), Week 8 (SVR8), Week 12 (SVR12), Week 24 (SVR24), and Week 36 (SVR36, for the 12 week arms) | 
| Proportion of treated subjects in each study population, by regimen, who achieve HCV RNA < LOQ (detectable/undetectable) |  | Weeks 1, 2, 4, 6, 8, 12 and End of Treatment (Week 12 or 24) | 
| Proportion of subjects in each study population, be regimen, who achieve HCV RNA undetectable |  | Weeks 1, 2, 4, 6, 8, 12 and End of Treatment (Week 12 or 24) | 
| Safety and tolerability of BMS-986094 and DCV ± RBV as measured by the frequency of deaths, serious adverse events (SAEs), discontinuations due to Adverse Events (AEs), and severity Grade 3/4 laboratory abnormalities |  | Up to post treatment Week 36 |