A Phase 3 Study to Evaluate Combination Therapy With Daclatasvir and Sofosbuvir in the Treatment of HIV and Hepatitis C Virus Coinfection.

Study Overview
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Brief Summary
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A study of the efficacy and safety of the combination of daclatasvir and sofosbuvir in the treatment of hepatitis C virus and HIV coinfection.

Official Title
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A Phase 3 Evaluation of Daclatasvir Plus Sofosbuvir in Treatment-naïve and Treatment-experienced Chronic Hepatitis C (Genotype 1, 2, 3, 4, 5, or 6) Subjects Coinfected With Human Immunodeficiency Virus (HIV)

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: Patients 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 Patients chronically infected with hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6, as documented by positive HCV RNA at screening Patients who are HCV treatment-naive Patients who are HCV treatment-experienced and who have had prior anti-HCV therapies discontinued or completed at least 12 weeks prior to screening Patients with HCV RNA ≥10,000 IU/mL at screening Patients with HIV-1 infection Key Exclusion Criteria: Presence of AIDs-defining opportunistic infections, as defined by the Centers of Disease Control and Prevention, within 12 weeks prior to study entry Patients infected with HIV-2 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 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daclatasvir + Sofosbuvir (Treatment-naive) 12 weeks<br>Treatment-naïve participants received daclatasvir 30, 60, or 90 mg, and sofosbuvir, 400 mg, once daily for 12 weeks | Drug: Daclatasvir<br> <br> * Other names: BMS-790052;Drug: Sofosbuvir<br> <br> |
| Experimental: Daclatasvir + Sofosbuvir (Treatment-naive) 8 weeks<br>Treatment-naïve participants received daclatasvir, 30, 60, or 90 mg, and sofosbuvir, 400 mg, once daily for 8 weeks | Drug: Daclatasvir<br> <br> * Other names: BMS-790052;Drug: Sofosbuvir<br> <br> |
| Experimental: Daclatasvir + Sofosbuvir (Treatment-experienced) 12 weeks<br>Treatment-experienced participants received daclatasvir, 30, 60, or 90 mg, and sofosbuvir, 400 mg, 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 Genotype 1 Hepatitis C Virus (HCV)-Infected Treatment-naive Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) | SVR12 was defined as HCV RNA <lower limit of quantitation, 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. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window. | At follow-up Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Hepatitis C Virus (HCV)/HIV-coinfected Treatment-naive Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) | SVR12 was defined as HCV RNA<lower limit of quantitation, 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. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window. | At follow-up Week 12 | 
| Percentage of Hepatitis C Virus (HCV)/HIV-coinfected Treatment-experienced Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12) | SVR12 was defined as HCV RNA <lower limit of quantitation, 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. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window. | At follow-up Week 12 | 
| Percentage of Participants of All Genotypes Coinfected With Hepatitis C Virus (HCV)/HIV Who Achieved Sustained Virologic Response Rate at Follow-up Week 12 (SVR12) | SVR12 was defined as HCV RNA levels <lower limit of quantitation, target detected or target not detected. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. For participants who missed the follow-up Week 12 visit, SVR12 was imputed using the next and closest available HCV RNA measurement after the follow-up Week 12 window. | At follow-up Week 12 | 
| Percentage of Participants Who Achieve Hepatitis C Virus RNA Levels to be <Lower Limit of Quantitation, Target Detected (TD)or Target Not Detected (TND) at Weeks: 1, 2, 4, 6, 8, and 12; at End of Treatment; and at Follow-up Weeks 4 and 24 | Participants with hepatitis C virus CV) levels to be <lower limit of quantitation, TD or TND at each visit. 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, and follow-up Week 4 and 24 | 
| Percentage of Participants Coinfected With Hepatitis C Virus/HIV Who Achieved HCV RNA Levels<Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) | Participants with HCV RNA levels <LLOQ, TND. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. | At Weeks 1, 2, 4, 6, 8, and 12 and at End of Treatment | 
| Percentage of Participants With CC or Non-CC Genotype at the IL28B rs12979860 Single Nucleotide Polymorphisms Who Achieved Sustained Virologic Response at Follow-up Week 12 (SVR12) | SVR is defined as hepatitis C virus RNA <lower limit of quantitation, target detected or target not detected at follow-up Week 12. Percentage calculated as number of responders/number of patients receiving treatment. | At Follow-up Week 12 | 
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Interruption or Discontinuation, Treatment-related AEs/SAEs and Grade 3 to 4 AEs/SAEs and Who Died During Treatment Period | AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may or may not 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. AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. | AEs: Day 1 to 7 days after last dose of study treatment (8 weeks or 12 weeks). SAEs: Day 1 to 30 days after last dose of study treatment (8 weeks or 12 weeks) | 
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-related AEs/SAEs, Grade 3 to 4 AEs/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 may or may not 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. AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. | AEs: Day 1 of follow-up period (Week 9 or Week 13) to 7 days after end of 24 weeks follow-up period. SAEs: Day 1 of follow-up period (Week 9 or Week 13) to 30 days after end of 24 weeks follow-up period. | 
| Number of Participants With Treatment-emergent Grade 3-4 Abnormalities on Laboratory Test Results | Grade 3-4 abnormalities on laboratory test results were defined as: International normalized ratio as 2.1-3.0*upper limit of normal (ULN) for grade 3 and >3.0*ULN for grade 4. Leukocytes as 1.0*10^9-1.5*10^9/L for grade 3 and <1.0*10^9/L for grade 4. Aspartate aminotransferase as 5.1-10.0*ULN for grade 3 and >10.0*ULN for grade 4. Bilirubin (total) as 2.6-5.0*ULN for grade 3 and >5.0*ULN for grade 4. Lipase (total) as 3.1-5.0*ULN for grade 3 and >5.0*ULN for grade 4. Alanine aminotransferase as 5.1-10.0*ULN for grade 3 and >10.0*ULN for grade 4. | From screening up to week 24 of post treatment follow--up |