Belatacept Therapy for the Failing Renal Allograft
Condition: Failing Renal Allograft
Intervention: Belatacept; Calcineurin inhibitor therapy; Mycophenolate mofetil; prednisone
Intervention description: Belatacept, dosing 10mg/kg- day 0, 2 weeks, 1 month, 2 months, 3 months; subsequent doses 5mg/kg monthly through duration of trial or until retransplantation, whichever is first.; Upon enrollment, wean calcineurin inhibitor (CNI) to target tacrolimus trough of 3-5 nanogram/milliliter (ng/ml)or equivalent cyclosporine trough. Upon initiation of hemodialysis, discontinue CNI therapy over 5 days.; Continue current dose at enrollment. Upon initiation of dialysis, decrease dose by half, then discontinue 2 weeks later; Begin steroid withdrawal one month after initiation of dialysis, with monthly reduction in dose by half, with plans to discontinue prednisone by 3 months after initiation of dialysis
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Prednisone; Abatacept; Tacrolimus; Cyclosporins; Calcineurin Inhibitors
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Kidney transplant

Summary:

      The purpose of this study is to test the safety and effectiveness of belatacept (Nulojix®) in
      preventing antibody formation in patients with chronic failing kidney transplants. This study
      is a randomized study of first-time kidney transplant patients who have worsening kidney
      function and biopsy proven grade 2 or 3 interstitial fibrosis/tubular atrophy (IF/TA).
      Patients must be eligible to get a second transplant. They must have completed or be actively
      undergoing evaluation for re-listing for a second transplant. Patients will be randomized to
      either convert to belatacept or continue on calcineurin inhibitor-based therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed written informed consent

          -  Kidney transplant recipient (human leukocyte antigen (HLA) non-identical donor) who
             now has impaired renal allograft function with:

          -  Estimated glomerular filtration rate (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:

          -  Women of childbearing potential (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 virus serum polymerase chain reaction (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.