Open-Label Phase 2 Trial of a Steroid-Free, CNI-Free, Belatacept-Based Immunosuppressive Regimen
Condition: Primary Renal Allograft Candidate; Kidney Transplantation
Intervention: Anti-thymocyte Globulin (Rabbit); belatacept; methylprednisolone; basiliximab; mycophenolate mofetil; tacrolimus
Intervention description: The target dosage is 6mg/kg total over 3 to 4 days. The recommended route of administration is intravenous infusion using a high-flow vein.; Participants will receive belatacept at a dose of 10mg/kg up on day 1, 5, 14, 28, 56 and 84. After 84 days, subjects will receive a maintenance dose of 5 mg/kg every 4 weeks until completion of the trial.; Methylprednisolone will be administered at a target dose of 500 mg beginning on the day of transplant, and tapered to 250 mg day 1 post-transplant, 125 mg day 2 post-transplant, 60 mg day 3 post-transplant, 30 mg day 4 post-transplant and day 5 post-transplant 0 mg if therapeutic tacrolimus level achieved for groups 1 and 3.; Basiliximab will be administered in two doses of 20 mg each.; Mycophenolate Mofetil will be administered at a target dose of 1000 mg orally twice a day. Myfortic® (mycophenolate sodium) may be used as a replacement for MMF. Mycophenolate sodium will be dosed at 720 mg PO BID. Mycophenolate sodium will be adjusted based on clinical complications.; The site investigator will identify a starting tacrolimus dose at their discretion, in order to achieve the target trough levels, no later than 5 days post-transplantation. The dose will be adjusted to 5-8ng/ml for the active comparator arm (thymoglobulin + tacrolimus + MMF arm) or tapered off in the experimental arm (basiliximab + 20 weeks of tacrolimus + MMF + belatacept).
Intervention MeSH terms: Mycophenolic Acid; Methylprednisolone; Abatacept; Tacrolimus; Thymoglobulin; Antilymphocyte Serum; Basiliximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 71.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Kidney Transplantation; Transplantation; NULOJIX; belatacept; chronic immunosuppression

Summary:

      The primary objective is to evaluate a NULOJIX® (belatacept) based regimens as a means of
      improving long-term graft function without increasing the risks of immunologic graft injury
      by avoiding both calcineurin inhibitors (CNIs) and corticosteroids.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or Female, 18-65 years of age at the time of enrollment;

          -  Ability to understand and provide written informed consent;

          -  Candidate for primary renal allograft from either living or deceased donor;

          -  No known contraindications to study therapy using NULOJIX® (belatacept);

          -  Female participants of childbearing potential must have a negative pregnancy test upon
             study entry;

          -  Participants with reproductive potential must agree to use an appropriate method(s) of
             birth control as outlined in the CellCept® , Myfortic® or generic package labeling
             during participation in the study and for 4 months following completion of the study;

          -  No donor specific antibodies prior to transplant that are considered to be of clinical
             significance by the site investigator;

          -  Negative crossmatch or Panel Reactive Antibodies (PRA) of 0% on historic and current
             sera, as determined by each participating study center;

          -  A documented negative tuberculosis (TB) test within the 6 months prior to transplant.
             If documentation is not present at the time of transplantation, and the subject does
             not have any risk factors for TB, a TB-specific interferon gamma release assay (IGRA)
             may be performed.

        Exclusion Criteria:

          -  Need for multi-organ transplant;

          -  Recipient of previous organ transplant;

          -  Epstein-Barr Virus (EBV) seronegative (or unknown) recipients;

          -  Active infection including hepatitis B, hepatitis C, or human Immunodeficiency Virus
             (HIV);

          -  Individuals who have required treatment with prednisone or other immunosuppressive
             drugs within 1 year prior to transplant;

          -  Individuals undergoing transplant using organs from extended criteria donor (ECD) or
             donation after cardiac death (DCD) donors;

          -  Histocompatibility antigen (HLA) identical living donors;

          -  Individuals at significant risk of early recurrence of the primary renal disease
             including focal segmental glomerulosclerosis (FSGS) and membranoproliferative
             glomerulonephritis (MPGN) type 2 or any other disease that in the opinion of the
             investigator is at increased likelihood of recurrence and which may result in rapid
             decline in renal function;

          -  Known history of thrombotic events or risk factors, including any of the following:

               -  Factor V Leiden, elevated homocysteine, positive lupus anticoagulant, elevated
                  anticardiolipin antibody, heparin-induced thrombocytopenia,

               -  A family history of a heritable thrombotic condition,

               -  Recurrent deep vein thrombosis (DVT) or pulmonary emboli (PE),

               -  Unexplained stillborn infant or recurrent spontaneous abortion or other
                  congenital or acquired thrombotic disorder.

        At the discretion of the investigator, a history of thrombosis of a dialysis access graft,
        fistula, or indwelling catheter/device may not be considered an exclusion criterion.

          -  Any condition that, in the opinion of the investigator, would interfere with the
             participant's ability to comply with study requirements;

          -  Use of investigational drugs within 4 weeks of enrollment;

          -  Known hypersensitivity to mycophenolate mofetil (MMF)or any of the drug's components;

          -  Administration of live attenuated vaccine(s) within 8 weeks of enrollment;

          -  Blood type A2 and A2B donors into blood type B recipients.