Phase III Daclatasvir and Sofosbuvir for Genotype 3 Chronic HCV

Study Overview
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Brief Summary
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To study the combination of Daclatasvir and Sofosbuvir for the treatment of hepatitis C virus (HCV) Genotype 3 infection

Official Title
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A Phase 3 Evaluation of Daclatasvir and Sofosbuvir in Treatment Naive and Treatment Experienced Subjects With Genotype 3 Chronic Hepatitis C Infection

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Daclatasvir
* Drug: Sofosbuvir


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 Key Inclusion Criteria: Subjects must be able to understand and agree to comply with the prescribed dosing regimens and procedures, report for regularly scheduled study visits, and reliably communicate with study personnel about adverse events and concomitant medications Subjects chronically infected with hepatitis C virus (HCV) genotype 3 Subjects who are HCV treatment-naive Subjects who are HCV treatment-experienced (previous exposure to non-structural 5A inhibitors is prohibited) HCV RNA ≥10,000 IU/mL at screening Key Exclusion Criteria: HCV Genotypes other than genotype-3 infection; mixed genotype infections are not permitted Liver or any other organ transplant (including hematopoietic stem cell transplants) other than cornea and hair Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to screening Documented or suspected hepatocellular carcinoma, as evidenced by previously obtained imaging studies or liver biopsy (or on a screening imaging study/liver biopsy if this was performed) Evidence of decompensated liver disease including, but not limited to, radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1:Daclatasvir + Sofosbuvir in treatment-naive subjects<br>Daclatasvir 60 mg tablet and Sofosbuvir 400 mg tablet orally once daily for 12 weeks | Drug: Daclatasvir<br> <br> * Other names: BMS-790052;Drug: Sofosbuvir<br> <br> |
| Experimental: A2:Daclatasvir + Sofosbuvir in treatment-experienced subjects<br>Daclatasvir 60 mg tablet and Sofosbuvir 400 mg tablet orally once daily for 12 weeks | Drug: Daclatasvir<br> <br> * Other names: BMS-790052;Drug: Sofosbuvir<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Treatment-Naive Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) Target Detected (TD) or Target Not Detected (TND) | SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation ie., 25 IU/mL, TD or TND at follow-up Week 12. HCV RNA levels were measured by the Roche Cobas® TaqMan® HCV Test version 2.0 from the central laboratory. | Week 12 (Follow-up period) | 
| Percentage of Treatment-Experienced Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) Target Detected (TD) or Target Not Detected (TND) | SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation ie., 25 IU/mL, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. | Week 12 (Follow-up period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Rapid Virologic Response at Week 4 (RVR) Target Not Detected (TND) | RVR was defined as hepatitis C virus RNA levels to be < lower limit of quantitation ie, 25 IU/mL TND at Week 4. 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) Target Not Detected (TND) | cEVR was defined as hepatitis C virus RNA levels to be < lower limit of quantitation ie, 25 IU/mL TND at Week 12. 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 End of Treatment Response (EOTR) Target Not Detected (TND) | EOTR were defined as hepatitis C virus RNA levels to be < lower limit of quantitation ie, 25 IU/mL TND at end of treatment. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. | Up to the end of treatment (up to 24 weeks) | 
| Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Less Than the Lower Limit of Quantitation (LLOQ) - Target Not Detected (TND) | Percentage of participants who achieved HCV RNA <LLOQ, TND was determined (LLOQ: 25 IU/mL). HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. | Week 1, 2, 6, 8 (treatment period) | 
| Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Less Than the Lower Limit of Quantitation (LLOQ)- Target Detected (TD) or Target Not Detected (TND) | Percentage of participants who achieved HCV RNA <LLOQ,TD or TND was determined (LLOQ: 25 IU/mL). HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. | Week 1, 2, 4, 6, 8, 12, End of treatment (treatment period), Week 4 (follow-up period), Week 24 (follow-up period) | 
| Percentage of Participants With Or Without Cirrhosis at Baseline Who Achieved Sustained Virologic Response at Follow-up Week 12 (SVR12) | SVR12 was defined as hepatitis C virus (HCV) RNA less than the lower limit of quantitation ie. 25 IU/mL, target detected or target not detected at follow-up Week 12. Cirrhosis was considered a negative predictor of SVR in participants treated with an interferon formulation or ribavirin. Presence or absence of cirrhosis was determined at baseline and follow-up Week 12 in the participants to evaluate the post-treatment relapse. | Baseline, Week 12 (Follow-up period) | 
| Percentage of Participants With CC or Non-CC Genotype at the IL28B rs12979860 Single Nucleotide Polymorphisms (SNPs) Who Achieved Sustained Virologic Response After 12 Weeks of Follow-up (SVR12) | Participants categorized into 2 genotypes (CC and non-CC) based on SNPs in the IL28B gene were assessed for SVR12, defined as response in which hepatitis C virus (HCV) RNA levels below lower limit of quantitation (LLOQ) below target detected or target not detected at follow-up Week 12 (LLOQ: 25 IU/mL). HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. | Week 12 (Follow-up period) | 
| Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) | 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 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 Day 1 first dose to last dose plus 7 days |