A Study in Maintenance Kidney Transplant Recipients Following Conversion to Nulojix® (Belatacept)-Based

Study Overview
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Brief Summary
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The primary purpose is to assess the benefits and risks of changing from Cyclosporine or Tacrolimus to Belatacept between 6-60 months after kidney transplant.

Official Title
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Evaluation of the Benefits and Risks in Maintenance Renal Transplant Recipients Following Conversion to Nulojix® (Belatacept)-Based Immunosuppression

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: Belatacept
* Drug: Tacrolimus
* Drug: Cyclosporine


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: Men and women, ages 18-75 inclusive Adult recipients of a renal allograft from a living donor or a deceased donor between 6-60 months prior to enrollment Receiving a stable (≥1 month) regimen of Calcineurin inhibitor (CNI) [Cyclosporine A (CsA) or Tacrolimus (TAC)] with Mycophenolate mofetil (MMF) or Enteric Coated Mycophenolate Sodium (EC-MPS)/Mycophenolic acid (MPA), and corticosteroids Stable renal function for 12 weeks prior to enrollment without new onset proteinuria Calculated glomerular filtration rate (cGFR) ≥30 and ≤75 mL/min/1.73 m2 [Modification of Diet in Renal Disease study (MDRD) 4-formula] Exclusion Criteria: Recipients with Epstein-Barr virus (EBV) serostatus negative or unknown History of acute rejection (AR) within 3 months prior to enrollment History of antibody mediated rejection Positive T-cell lymphocytotoxic cross match Proteinuria >1 g/day or >0.5 g/day if diabetic

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Belatacept<br>Belatacept 5 mg/kg intravenous 30 minute infusion on Days 1, 15, 29, 43, 57 then every 28 days for 24 months | Drug: Belatacept<br> <br> * Other names: Nulojix®;|
| Active Comparator: CNI<br>Tacrolimus 4-11 ng/mL tablet orally according to package insert for 24 months Cyclosporine 50-250 ng/mL tablet orally according to package insert for 24 months | Drug: Tacrolimus<br> <br> Drug: Cyclosporine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Survive With a Functional Graft at 24 Months | Percentage of participants who survive with a functional graft at 24 months post-randomization | at 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Survive With a Functional Graft at 12 Months | Percentage of participants who survive with a functional graft at 12 months post-randomization | at 12 Months | 
| Number of Participants With a Biopsy Proven Acute Rejection (BPAR) | The number of clinically suspected, biopsy proven acute rejection (AR) at 12 and 24 months post-randomization includes participants with at least one cellular and/or humoral BPAR event. | at 12 and 24 Months | 
| Number of Participants With Varying Severity of BPAR | Number of participants in each severity of clinically suspected, biopsy proven acute rejection (AR) at 12 and 24 months post-randomization | at 12 and 24 months | 
| Mean Change From Baseline of Calculated Glomerular Filtration Rate (cGFR) - Percent Change | Mean change from baseline cGFR as calculated by the 4-variable MDRD equation to 12 and 24 months post-randomization - Percent Change | at 12 and 24 months | 
| Mean Change From Baseline of Calculated Glomerular Filtration Rate (cGFR) - Adjusted Change | Mean change from baseline cGFR as calculated by the 4-variable MDRD equation to 12 and 24 months post-randomization - Adjusted Change | at 12 and 24 months | 
| Mean Calculated Glomerular Filtration Rate (cGFR) | Mean cGFR by study visit, as calculated by the 4-variable MDRD equation. | up to 24 months | 
| Slope Analysis of cGFR | Slopes of cGFR as plotted from baseline as well as from Month 3, to Month 12 and Month 24 post-randomization | at 12 and 24 Months | 
| Slope Analysis of 1/Serum Creatinine | Slopes of 1/serum creatinine as plotted from baseline as well as from Month 3, to Month 12 and Month 24 post-randomization | at 12 and 24 Months | 
| Percentage of Participants With > 5% and >10% Improvement Over Baseline cGFR | Percentage of participants with > 5% and >10% improvement over baseline cGFR, at 12 and 24 months post-randomization | at 12 and 24 Months | 
| Mean Urine Protein/ Creatinine Ratio (UPCR) | Urine protein/ creatinine ratio (UPCR) at baseline, 3, 6, 12 and 24 months post randomization | Up to 24 Months | 
| Mean Change From Baseline in Systolic and Diastolic Blood Pressure | Mean change in systolic and diastolic blood pressure from baseline to 12 and 24 months post randomization | at 12 and 24 months | 
| Number of Antihypertensive Medications Used to Control Hypertension | The total number of antihypertensive medications used to control hypertension | at baseline, 12 and 24 Months | 
| Number of Participants With Donor Specific Antibodies (DSA) | Number of participants with donor specific antibodies (DSA) at Baseline/Day 1, and Months 12 and 24 post-randomization | at baseline, 12 and 24 months | 
| Mean Number of Symptom Occurrence and Symptom Distress | The frequency of symptom occurrence and symptom distress as measured with the Modified Transplant Symptom Occurrence and Symptom Distress Scale-59R (MTSOSD-59R) at baseline, Week 6, and Months 3, 6, and 12 post-randomization. Higher scores in the MTSOSD-59R indicate a greater symptom and symptom distress burden than lower scores. | up to 12 Months | 
| Number of Participants With an Adverse Event of Special Interest | Number of participants with an adverse event of special interests. Adverse events of special interest include: Serious Infections, Post-Transplant Lymphoproliferative Disorder (PTLD), Progressive multifocal leukoencephalopathy (PML), Malignancies (other than PTLD) including non-melanoma skin carcinomas, Tuberculosis Infections, CNS infections, Viral Infections and Infusion related reactions. | 24 Months | 
| Number of Participants With Marked Laboratory Abnormalities | Number of participants with Marked Laboratory Abnormalities | 24 Months | 
| Mean Change From Baseline in Vital Signs: Heart Rate | The mean change from baseline in measured heart rate | at 12 and 24 months |