Advancing Transplantation Outcomes in Children

Open to people ages 13-20

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) at time of enrollment
5. If a female participant of childbearing potential, a negative pregnancy test within 48 hours of enrollment
6. If participant has reproductive potential, agrees to use Food and Drug Administration (FDA) approved methods of birth control for the duration of the study
7. 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

8. 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.

1. Inability or unwillingness to comply with study protocol
2. Active infection requiring treatment, or viremia
3. History of malignancy
4. Current or historical anti-HLA antibody to the donor
5. Peak calculated Panel Reactive Antibody (cPRA) greater than 80 percent
6. Receipt of any licensed or investigational live attenuated vaccine(s) within 4 weeks of enrollment
7. Prior history of organ transplantation
8. Active systemic autoimmune disease at time of enrollment

9. Idiopathic Focal Segmental Glomerulosclerosis (FSGS), Membranoproliferative Glomerulonephritis (MPGN), C3 glomerulopathy, or atypical Hemolytic Uremic Syndrome (HUS) suspected at risk for recurrence

   10. Use of immunosuppressants, biologics (including IVIG), chronic corticosteroids or

   investigational drug(s) within 8 weeks of enrollment

   11. Known bleeding disorder 12. Platelet count < 75,000 cells/microliters within 3 months of enrollment 13. History of inherited hypercoagulability requiring therapy more than aspirin 14. Clinically significant unrepaired congenital heart disease causing hemodynamic

   compromise

   15. 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

   16. 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 Exclusion Criteria: Individuals who meet any of these criteria are not eligible for randomization.

10. Sustained WBC <1500 or >20,000 per microliter within 3 months of randomization
11. Sustained liver function tests (AST and/or ALT) > 2x normal within 3 months of randomization
12. Active systemic autoimmune disease at time of transplant
13. Known bleeding disorder
14. Platelet count < 75,000 cells/microliters within 3 months of enrollment
15. Current or historical anti-HLA antibody to the donor at the time of transplant
16. Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of randomization
17. Panel Reactive Antibody (cPRA) greater than 80 percent

18. 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