Evaluation of the Benefits and Risks in Maintenance Renal Transplant Recipients Following Conversion to Nulojix® (belatacept)-based Immunosuppression

There is no formal research hypothesis for this study. The purpose of this
study is to assess
the safety and efficacy of conversion from CNI to belatacept in stable EBV+
adult recipients of a renal allograft
from a living donor or a deceased donor between 6 - 36 months prior to
enrollment.

Primary
1. To evaluate patient and functional graft survival in stable renal transplant
recipients (6-60 months post transplantation) converted from CNI to
belatacept-based immunosupression as compared to those continuation of CNI
based immunosuppression at 24 months post-randomization.

Secondary
To evaluate the effect of conversion from CNI to belatacept on the following:
1. Composite of patient and functional graft survival at 12 months
post-randomization
2. The incidence and severity of clinically suspected biopsy-proven acute
rejection at 12 and 24 months post- randomization
3. Renal function as assessed by:
- Mean change in cGFR (MDRD) from baseline to D1-12/24 months
post-randomization (% and absolute)
- Slopes of cGFR and 1/serum creatinine respectively from baseline as well as
Month 3 to 12 and 24 months post-randomization
- Proportion of subjects with > 5% and > 10% improvement over baseline in cGFR
at 12 and 24 months post-randomization
- Urine protein/ creatinine ratio (UPCR) at baseline, 3, 6, 12, and 24 months
post-randomization
4. Mean change in systolic and diastolic blood pressure and intensity of
treatment regimen from baseline to 12 and 24 months post-randomization
5. Incidence of donor specific antibodies (DSA) at Baseline/Day 1, Months 12
and 24 post-randomization
6. Occurrence of symptom occurrence and symptom distress measured with the
MTSOSDS-R 59 at baseline, week 6, and Months 3, 6, and 12 post- randomization
7. Safety and tolerability of a belatacept-based immunosuppressive regimen

This is a randomized, open-label, active-controlled, parallel-group study.
Approximately 440 subjects on CNI-based regimens will be randomized in a 1:1
ratio to treatment with either belatacept or continued treatment with their
established CNI. All subjects will also receive a background maintenance
immunosuppressive regimen of mycophenolate mofetil (MMF) or mycophenolic acid
(MPA), with adjunctive daily corticosteroids, according to their
immunosuppressive regimen at the time of enrollment. Enrollment will be
monitored, and if necessary restricted, to ensure no more than 25% of patients
are maintained on CsA at enrollment. In addition, participation by patients
receiving the maintenance immunosuppressive combination of tacrolimus with
mycophenolate sodium will be limited to no more than approximately 1/3 of all
subjects.

A 1 month lead-in will be employed to confirm a stable CNI (TAC or CsA) trough
concentration. A serum creatinine (SCr) value within 3 months of enrollment and
within ±10% of the screening SCr value is required to confirm stable renal
function. Subjects will be stratified by site and baseline cGFR (* 30 to < 45
mL/min/1.73 m2 or * 45 to 75 mL/min/1.73 m2). Subjects will also be randomized
with a 1:2 ratio for baseline cGFR * 30 to < 45 mL/min/1.73 m2 or * 45 to 75
mL/min/1.73 m2. Subjects with a baseline cGFR > 60 mL/min/1.73 m2 must have
documentation of CNI toxicity to be included in the study.

Group 1: Convert to Belatacept in doses of 5 mg/kg intravenous
Group 2: Continue established CNI treatment twice daily doses by mouth as
directed

NA