Advancing Transplantation Outcomes in Children

Purpose

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.

Condition

  • Kidney Transplant

Eligibility

Eligible Ages
Between 13 Years and 20 Years
Eligible Genders
All
Accepts 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 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 (within 30 days) or historical anti-HLA antibody to the donor 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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
(Group 1): Belatacept+Sirolimus group 		Participants in this group will receive antithymocyte globulin (ATG) + steroid taper + belatacept + (tacrolimus bridge, day 0-14) with conversion to sirolimus (day 30 +/-14 days)
  • Drug: Sirolimus
    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
    Other names:
    • AY 22-989
    • Rapamune
    • Rapamycin
  • Biological: Belatacept
    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
    Other names:
    • Nulojix
  • Drug: Tacrolimus (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
    Other names:
    • FK-506
    • FR-900506
    • Prograf
  • Drug: Anti-Thymocyte Globulin (ATG)
    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
Active Comparator
(Group 2): Tacrolimus + Mycophenolate Mofetil (MMF) group 		Participants in this group will receive anti-thymocyte globulin (ATG) + steroid taper + tacrolimus + MMF
  • Drug: Mycophenolate 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
    Other names:
    • CellCept
    • MMF
  • Drug: Anti-Thymocyte Globulin (ATG)
    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
  • Drug: Tacrolimus (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
    Other names:
    • FK-506
    • FR-900506
    • Prograf

Recruiting Locations

University of Alabama at Birmingham (Site # 71038)
Birmingham, Alabama 35233
Contact:
Scott House
205-638-9781
whouse@uabmc.edu

More Details

Status
Recruiting
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Study Contact