Overview

This is a pediatric kidney transplant study comparing the safety and efficacy of an immunosuppressive regimen of belatacept and sirolimus to tacrolimus and Mycophenolate Mofetil (MMF). Two hundred participants will be randomized (1:1) to one of two groups within 24 hours following the transplant procedure. The duration of the study from time of transplant to the primary endpoint is 12-24 months.

Eligibility

Inclusion Criteria:

1. Participant and/or parent/guardian must be able to understand and provide informed consent
2. Male or female, 13-20 years of age at time of enrollment
3. Candidate for primary renal allograft from a deceased donor
4. EBV IgG seropositive, defined as evidence of acquired immunity shown by the presence of IgG antibodies to viral capsid antigen (VCA) and EBV nuclear antigen (EBNA)
5. EBV VCA IgM seronegative
6. If a female participant of childbearing potential, a negative pregnancy test within 48 hours of enrollment
7. If participant has reproductive potential, agrees to use Food and Drug Administration (FDA) approved methods of birth control for the duration of the study
8. Negative test result for latent tuberculosis infection by tuberculosis skin test (purified protein derivative [PPD]) or Tuberculosis (TB) blood test (interferon gamma release assay [IGRA] i.e., QuantiFERON, T- SPOT.TB) within 12 months
9. In the absence of contraindication, vaccinations must be up to date per the Centers for Disease Control and Prevention (CDC) Guidelines and Division of Allergy, Immunology, and Transplantation (DAIT) Guidance for Patients in Transplant Trials

        Enrollment criteria for donor source and age will be expanded using a stepwise approach
        determined by safety monitoring. Expansion criteria will include recipients down to age 6
        and living donors. Safety data from each step will be reviewed by the study team, DSMB and
        FDA. If no safety concerns are identified, inclusion criteria will be expanded.
        Exclusion Criteria:
          1. Inability or unwillingness to comply with study protocol
          2. Active infection requiring treatment, or viremia
          3. History of malignancy
          4. Receipt of any licensed or investigational live attenuated vaccine(s) within 4 weeks
             of enrollment
          5. Prior history of organ transplantation
          6. Active systemic autoimmune disease at time of enrollment
          7. Idiopathic Focal Segmental Glomerulosclerosis (FSGS), Membranoproliferative
             Glomerulonephritis (MPGN), C3 glomerulopathy, or atypical Hemolytic Uremic Syndrome
             (HUS) suspected at risk for recurrence
          8. Use of immunosuppressants, biologics (including IVIG), chronic corticosteroids or
             investigational drug(s) within 8 weeks of enrollment
          9. Known bleeding disorder
         10. Sustained platelet count < 75,000 cells/microliters within 3 months of enrollment
         11. History of inherited hypercoagulability requiring therapy more than aspirin
         12. Clinically significant unrepaired congenital heart disease causing hemodynamic
             compromise
         13. Uncontrolled diagnosed psychiatric disorder or self-reported drug or alcohol abuse
             that, in the opinion of the investigator, would interfere with the participant's
             ability to comply with study requirements
         14. Past or current medical problems or findings from physical examination or laboratory
             testing that are not listed above, which, in the opinion of the investigator, may pose
             additional risks from participation in the study, may interfere with the participant's
             ability to comply with study requirements or that may impact the quality or
             interpretation of the data obtained from the study
        Randomization Inclusion Criteria:
        Individuals who meet all of the following criteria are eligible for randomization.
          1. EBV VCA IgG and EBV EBNA IgG seropositive, confirmed between enrollment and time of
             transplant
          2. EBV VCA IgM seronegative, confirmed between enrollment and time of transplant
        Randomization Exclusion Criteria:
        Individuals who meet any of these criteria are not eligible for randomization.
          1. Sustained WBC <1500 or >20,000 per microliter within 3 months of randomization
          2. Sustained liver function tests (AST and/or ALT) > 2x normal within 3 months of
             randomization
          3. Active systemic autoimmune disease at time of transplant
          4. Known bleeding disorder
          5. Sustained platelet count < 75,000 cells/microliters within 3 months of enrollment
          6. Current or historical anti-HLA antibody to the donor at the time of transplant within
             30 days prior to randomization
          7. Recent recipient of any licensed or investigational live attenuated vaccine(s) within
             4 weeks of randomization
          8. Panel Reactive Antibody (cPRA) greater than 80 percent
          9. If a female participant of childbearing potential, a positive pregnancy test within 48
             hours of randomization (all female participants of childbearing potential must
             complete a pregnancy test within 48 hours of randomization)
         10. Treatment with immunosuppressants, including biologics (including IVIG), within 8
             weeks of randomization