Kidney Transplant
Conditions
Keywords
kidney transplant, belatacept, sirolimus
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.
Interventions
DRUGSirolimus
Participants in Group 1 will transition to sirolimus therapy on day 14 (+/- 5 days) - weight \<40 kg will receive 3mg/m\^ 2, with maintenance dose of 1 mg/m\^2 divided BID - weight \>= 40kg will receive 6mg/m\^ 2, with maintenance dose of 2 mg daily
BIOLOGICALBelatacept
Belatacept will be administered as an intravenous infusion over 30 minutes. The belatacept dose for the study is 10 mg/kg on post-operative day (POD) 1, 5, 14, 28, 56, 84 for the first 3 months, followed by 5 mg/kg every 4 weeks (+/-4 days), starting on month 4 until month 24
DRUGMycophenolate Mofetil
Mycophenolate Mofetil-MMF will be initiated at 600 mg/m\^2 BID until tacrolimus is at therapeutic levels, then 450 mg/m\^2 BID
DRUGTacrolimus (Group1)
Participants will receive Prograf® (tacrolimus), or generic, initiated at 0.1 mg/kg BID within 48 hours of transplantation to attain target trough levels. Participants in Group 1 will be transitioned to sirolimus 2-4 weeks post-transplant
Participants will receive induction therapy with anti-thymocyte globulin (1.5 mg/kg/dose, maximum 125 mg) starting intraoperatively on day 0 and continuing on days 2 and 3 (total dose 4.5 mg/kg). Total dose may be extended to 6 mg/kg over 1-2 days for delayed graft function
DRUGTacrolimus (Group 2)
Participants will receive Prograf® (tacrolimus), or generic, initiated at 0.1 mg/kg BID within 48 hours of transplantation to attain target trough levels
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 20 Years
Healthy volunteers
No
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 living or 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 OR EBV VCA IgM seropositive on two occasions at least 3 months apart and an undetectable EBV PCR result within 1 month prior to enrollment 6. If a female participant of childbearing potential, a negative pregnancy test prior to conducting any study procedures 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. Listed for multi-organ transplant (e.g. heart- kidney, liver-kidney, multivisceral- kidney, lung- kidney) 7. Active systemic autoimmune disease at time of enrollment 8. Idiopathic Focal Segmental Glomerulosclerosis (FSGS), Membranoproliferative Glomerulonephritis (MPGN), C3 glomerulopathy, or atypical Hemolytic Uremic Syndrome (HUS) suspected at risk for recurrence 9. Use of immunosuppressants, biologics (including IVIG), chronic corticosteroids or investigational drug(s) within 8 weeks of enrollment 10. Known bleeding disorder 11. Sustained platelet count \< 75,000 cells/microliters within 3 months of enrollment 12. History of inherited hypercoagulability requiring therapy more than aspirin 13. Panel Reactive Antibody (cPRA) greater than 80 percent 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 Inclusion Criteria: Individuals who meet all of the following criteria are eligible for randomization. 1\. If EBV serology to meet enrollment criteria was performed within 8 weeks of receiving IVIG, EBV VCA IgG and EBV EBNA IgG seropositivity, confirmed between enrollment and time of transplant Randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of de novo Donor Specific Antibody (dnDSA) (central lab) OR decline in estimated glomerular filtration rate (eGFR) >7.5 mL/min/1.73m^2 (central lab) | At 96 weeks post-transplant |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of clinical biopsy proven allograft rejection (central lab) | Within 96 weeks post-transplant |
| Time to development of clinical biopsy proven allograft rejection (central lab) | Within 96 weeks post-transplant |
| Incidence of subclinical biopsy proven allograft rejection (central lab) | Within 96 weeks post-transplant |
| Time to development of subclinical biopsy proven allograft rejection (central lab) | Within 96 weeks post-transplant |
| Incidence of Post-Transplant Lymphoproliferative Disease (PTLD) | Within 96 weeks post-transplant |
| Time to development of the PTLD | Within 96 weeks post-transplant |
| Incidence of Grade 3 and above opportunistic infections bacterial, viral, fungal, pneumocystis pneumonia, or parasitic infections assessed as a composite | Within 96 weeks post-transplant |
| Time to development of Grade 3 and above opportunistic infections bacterial, viral, fungal, pneumocystis pneumonia, or parasitic infections assessed as a composite | Within 96 weeks post-transplant |
Countries
United States
Contacts
STUDY_CHAIRDavid Briscoe, MD
Boston Children's Hospital: Pediatric Transplantation
STUDY_CHAIREileen Chambers, MD
Duke University Medical Center: Department of Pediatrics
Outcome results
None listed