Belatacept Therapy for the Failing Renal Allograft

The purpose of this study is to test the safety and effectiveness of the medicine belatacept
(Nulojix®) in preventing antibodies from forming in people with a failing kidney transplant.
Kidney transplant patients take immunosuppression medicines to prevent kidney rejection. When
a kidney transplant begins to fail, the immunosuppression medicines are slowly weaned. Once
dialysis is started, the immunosuppressant medicines are usually stopped. After
immunosuppression is stopped, some people form antibodies. Antibodies are proteins that the
immune system makes to protect against harmful foreign substances like bacteria, viruses, or
foreign tissues, like a transplant. High levels of antibodies can make it harder to find a
kidney donor for that person.

Participants will be randomized into one of the two treatment groups. One group will continue
taking their current immunosuppression medicines. The people in the treatment group will be
switched to belatacept (Nulojix®). Belatacept (Nulojix®) is an immunosuppression medicine
that is approved by the U.S. Food and Drug Administration (the FDA) to prevent rejection in
kidney transplant. Participants will stop taking calcineurin inhibitors (either cyclosporine
or tacrolimus) or sirolimus but will keep taking other immunosuppression medicines like
Cellcept (MMF) or azathioprine (Imuran) and prednisone. These medicines will be slowly weaned
and will be stopped if the participant has to start dialysis. Participants will continue
taking belatacept (Nulojix®), even while on dialysis.

The study team will test both groups to see how many people in each group develop antibodies.

Inclusion Criteria:

- Signed Written Informed Consent

- Kidney transplant recipient (non-HLA identical donor) who now has impaired renal
allograft function with:

- Estimated GFR < 35 with a decline in GFR of > 10% in the 12 months prior to enrollment
and must have biopsy proven grade II or III interstitial fibrosis/tubular atrophy
(IF/TA) OR

- Estimated GFR persistently < 20 ml/min over the 6 month period prior to enrollment
absent other causes for graft dysfunction, and deemed to have a failing allograft by
the patient's transplant nephrologist

- On a maintenance immunosuppressive regimen that includes calcineurin inhibitor
(CNI)(tacrolimus or cyclosporine) or sirolimus and at least

- MMF of a dose of at least 1 gm/day or comparable dose of azathioprine OR

- Prednisone at a dose of at least 5 mg/day

- Men and women, ages 18 to 70, inclusive

Exclusion Criteria:

- WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for
the entire study period and for up to 8 weeks after the last dose of study drug.

- Women who are pregnant or breastfeeding.

- Women with a positive pregnancy test.

- Sexually active fertile men not using effective birth control if their partners are
WOCBP.

- Subjects who are Epstein-Barr Virus (EBV) seronegative.

- Subjects with any prior solid organ (e.g., heart, liver, pancreas) or cell (e.g.,
islet, bone marrow) transplant other than a renal allograft. Exception may be made for
recipient of a simultaneous kidney-pancreas transplant who had previously experienced
graft loss of the pancreas allograft due to thrombosis or rejection.

- Subjects with presence of donor specific antibody at the time of enrollment

- Subjects who have a recent history (within 1 yr) of biopsy proven acute rejection >
Banff grade Ia

- Subjects who have a living donor identified for re-transplant within 3 months

- Subjects with a history of post-transplant lymphoproliferative disease (PTLD)

- Subjects at risk for tuberculosis (TB)

- Subjects with a history of cancer within the past 3 years, other than non-melanoma
skin cancer(s)

- Subjects with a positive BK serum PCR > 20,000 copies at the time of enrollment OR
history of biopsy-proven BK nephropathy within the year prior to enrollment.

- Subjects with a mammogram that is suspicious for malignancy and in whom the
possibility of malignancy cannot be reasonably excluded following additional clinical,
laboratory, or other diagnostic evaluations

- Subjects who have difficult intravenous access or other reasons that would likely
preclude the ability to receive long-term intravenous infusions

- Hypersensitivity to any medications that will be used in the protocol

- Subjects who have used any investigational drug within the 30 days prior to
anticipated enrollment

- Subjects currently receiving belatacept as part of their maintenance immunosuppressive
regimen

- Prisoners, or subjects who are involuntarily incarcerated.

- Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness.