Short Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis-C (FOURward Study)

Study Overview
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Brief Summary
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The purpose of the study is to determine whether the combination of Daclatasvir (DCV), Asunaprevir (ASV), BMS-791325 and Sofosbuvir is effective and safe in treating Hepatitis-C virus.

Detailed Description
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Allocation: Initial Therapy: Randomized Controlled Trial: Participants are assigned to intervention groups by chance Rescue Therapy: Nonrandomized Trial: Participants are expressly assigned to intervention groups through a non-random method such as physician choice Number of Arms: Initial Therapy: 2 Groups Rescue Therapy: 2 Groups

Official Title
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Short Duration Combination Therapy With Daclatasvir, Asunaprevir, BMS-791325 and Sofosbuvir in Subjects Infected With Chronic Hepatitis C (FOURward Study)

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: DCV/ASV/BMS-791325
* Drug: Ribavirin
* Drug: Sofosbuvir
* Drug: Peginterferon α-2a


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, inclusive Chronic HCV infection Genotype 1 only Non-cirrhotic Treatment naive subjects with no previous exposure to an Interferon formulation (ie, IFNα, pegIFNα), ribavirin (RBV) or HCV Direct Acting Antiviral (DAA) (protease, polymerase inhibitor, etc.) Exclusion Criteria: HCV Genotype other than Genotype 1 Documented or suspected hepatocellular carcinoma Evidence of decompensated liver disease Contraindication(s) to Peg/RBV therapy
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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: DCV/ASV/BMS-791325+Sofosbuvir<br>Initial Therapy: Daclatasvir/Asunaprevir/BMS-791325 [30 mg (as the free base)/200 mg/75 mg (as the free base)] film coated Fixed Dose Combination tablet twice daily orally for 4 weeks Sofosbuvir 400 mg tablet once daily orally for 4 weeks | Drug: DCV/ASV/BMS-791325<br> <br> Drug: Sofosbuvir<br> <br> * Other names: Sovaldi®;|
| Experimental: Arm 2: DCV/ASV/BMS-791325 + Sofosbuvir<br>Initial Therapy Daclatasvir/Asunaprevir/BMS-791325 [30 mg (as the free base)/200 mg/75 mg (as the free base)] film coated Fixed Dose Combination tablet twice daily orally for 6 weeks Sofosbuvir 400 mg tablet once daily orally for 6 weeks | Drug: DCV/ASV/BMS-791325<br> <br> Drug: Sofosbuvir<br> <br> * Other names: Sovaldi®;|
| Experimental: Rescue Therapy: Arm 1:DCV/ASV/BMS-791325+RBV±PegIFNα-2a<br>Daclatasvir/Asunaprevir/BMS-791325 [30 mg (as the free base)/200 mg/75 mg (as the free base)] film coated Fixed Dose Combination tablet twice daily orally for 12 weeks Ribavirin 200 mg tablets twice daily (1000 or 1200 mg per day based on weight) orally for 12 weeks With or without Peginterferon α-2a 180 µg solution for injection subcutaneously once weekly for 12 weeks | Drug: DCV/ASV/BMS-791325<br> <br> Drug: Ribavirin<br> <br> Drug: Peginterferon α-2a<br> <br> |
| Other: Rescue Therapy: Arm 2: Sofosbuvir + RBV + PegIFNα-2a<br>Sofosbuvir 400 mg tablet once daily orally for 12 weeks Ribavirin 200 mg tablets twice daily (1000 or 1200 mg per day based on weight) orally for 12 weeks Peginterferon α-2a 180 µg solution for injection subcutaneously once weekly for 12 weeks | Drug: Ribavirin<br> <br> Drug: Sofosbuvir<br> <br> * Other names: Sovaldi®;Drug: Peginterferon α-2a<br> <br> |

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 12 (SVR12) | SVR12 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 12. Imputed SVR12 was based on Next Value Carried Backwards approach. | 12 Weeks after treatment discontinuation (Follow-up Week 12) | 
| Number of Participants With Deaths, Serious Adverse Events (SAEs) and AEs Leading to Discontinuation From Treatment | SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/ birth defect. | From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months) | 
| Number of Participants With Selected Grade 3/4 Laboratory Abnormalities | Grade 3/4 laboratory abnormalities (hematology, electrolyte, lipase, liver function, metabolic, renal function, urinalysis). The Week 24 data set was used to evaluate the Week-24 on-treatment safety. The cumulative data set was used to evaluate the safety while on treatment. Common Terminology Criteria for Adverse Events v3.0 (CTCAE) Grades:1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death. | From signature of the informed consent until 4 weeks after last treatment administration.(Approximately 17 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With End of Treatment Response (EOTR) | EOTR was defined as HCV RNA less than the lower limit of quantitation, target detected or not detected at end of treatment. | End of the treatment | 
| Percentage of Participants Who Achieved HCV RNA <LLOQ TD/TND | Percentage of Participants with hepatitis C virus(HCV) ribonucleic acid (RNA) < lower limit of quantitation (LLOQ), target detected (TD) or target not detected (TND) were presented at treatment Weeks 1, 2, 4, 6, and follow-up Weeks 2 (SVR2), 4 (SVR4), 12 (SVR12) and 24 (SVR24). | Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2 (SVR2), 4 (SVR4), 12 (SVR12) and 24 (SVR24) | 
| Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Percentage of Participants with hepatitis C virus(HCV) ribonucleic acid (RNA) < lower limit of quantitation (LLOQ), target not detected (TND) were presented at treatment Weeks 1, 2, 4, 6, and follow-up Weeks 2 (SVR2), 4 (SVR4), and 24 (SVR24). | Treatment Weeks 1, 2, 4 and 6; post-treatment Weeks 2, 4, 12 and 24 | 
| Percentage of Participants Who Achieved SVR12 Associated With HCV Geno Subtype 1a vs 1b | Percentage of Participants who Achieved SVR12 Associated with HCV geno subtype 1a or 1b | Post-treatment Week 12 | 
| Percentage of Participants Who Achieved SVR12 Associated With Interleukin-28B (IL28B) rs12979860 SNP Status (CC Genotype or Non-CC Genotype) | Percentage of Participants who Achieved SVR12 Associated with IL28B rs12979860 Single Nucleotide Polymorphisms (SNP) status (CC genotype or non CC genotype) were reported. | Post-treatment Week 12 |