Advancing Transplantation Outcomes in Children

About

Brief Summary

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.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 2

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

13 Years

Maximum Age

20 Years

Inclusion Criteria:

Participant and/or parent/guardian must be able to understand and provide informed consent
Male or female, 13-20 years of age at time of enrollment
Candidate for primary renal allograft from a deceased donor
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)
EBV VCA IgM seronegative
If a female participant of childbearing potential, a negative pregnancy test within 48 hours of enrollment
If participant has reproductive potential, agrees to use Food and Drug Administration (FDA) approved methods of birth control for the duration of the study
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
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:

Inability or unwillingness to comply with study protocol
Active infection requiring treatment, or viremia
History of malignancy
Receipt of any licensed or investigational live attenuated vaccine(s) within 4 weeks of enrollment
Prior history of organ transplantation
Active systemic autoimmune disease at time of enrollment
Idiopathic Focal Segmental Glomerulosclerosis (FSGS), Membranoproliferative Glomerulonephritis (MPGN), C3 glomerulopathy, or atypical Hemolytic Uremic Syndrome (HUS) suspected at risk for recurrence
Use of immunosuppressants, biologics (including IVIG), chronic corticosteroids or investigational drug(s) within 8 weeks of enrollment
Known bleeding disorder
Sustained platelet count < 75,000 cells/microliters within 3 months of enrollment
History of inherited hypercoagulability requiring therapy more than aspirin
Clinically significant unrepaired congenital heart disease causing hemodynamic compromise
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
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.

EBV VCA IgG and EBV EBNA IgG seropositive, confirmed between enrollment and time of transplant
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.

Sustained WBC <1500 or >20,000 per microliter within 3 months of randomization
Sustained liver function tests (AST and/or ALT) > 2x normal within 3 months of randomization
Active systemic autoimmune disease at time of transplant
Known bleeding disorder
Sustained platelet count < 75,000 cells/microliters within 3 months of enrollment
Current or historical anti-HLA antibody to the donor at the time of transplant within 30 days prior to randomization
Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of randomization
Panel Reactive Antibody (cPRA) greater than 80 percent
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)
Treatment with immunosuppressants, including biologics (including IVIG), within 8 weeks of randomization