Advancing Transplantation Outcomes in Children
- Registration Number
- NCT06055608
- 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...
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
- 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.
- 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 (within 30 days) or historical anti-HLA antibody to the donor 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description (Group 1): Belatacept+Sirolimus group Tacrolimus (Group1) 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) (Group 1): Belatacept+Sirolimus group Anti-Thymocyte Globulin (ATG) 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) (Group 2): Tacrolimus + Mycophenolate Mofetil (MMF) group Anti-Thymocyte Globulin (ATG) Participants in this group will receive anti-thymocyte globulin (ATG) + steroid taper + tacrolimus + MMF (Group 2): Tacrolimus + Mycophenolate Mofetil (MMF) group Tacrolimus (Group 2) Participants in this group will receive anti-thymocyte globulin (ATG) + steroid taper + tacrolimus + MMF (Group 1): Belatacept+Sirolimus group Sirolimus 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) (Group 1): Belatacept+Sirolimus group Belatacept 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) (Group 2): Tacrolimus + Mycophenolate Mofetil (MMF) group Mycophenolate Mofetil Participants in this group will receive anti-thymocyte globulin (ATG) + steroid taper + tacrolimus + MMF
- Primary Outcome Measures
Name Time Method 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 2 years post-transplant
- Secondary Outcome Measures
Name Time Method Incidence of Post-Transplant Lymphoproliferative Disease (PTLD) Within 2 years post-transplant Incidence of clinical biopsy proven allograft rejection (central lab) Within 2 years post-transplant Time to development of subclinical biopsy proven allograft rejection (central lab) Within 2 years post-transplant Incidence of Grade 3 and above opportunistic infections bacterial, viral, fungal, pneumocystis pneumonia, or parasitic infections assessed as a composite Within 2 years post-transplant Time to development of the PTLD Within 2 years 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 2 years post-transplant Time to development of clinical biopsy proven allograft rejection (central lab) Within 2 years post-transplant Incidence of subclinical biopsy proven allograft rejection (central lab) Within 2 years post-transplant
Trial Locations
- Locations (21)
University of Alabama at Birmingham (Site # 71038)
🇺🇸Birmingham, Alabama, United States
Children's Hospital of Los Angeles (Site #: 71036)
🇺🇸Los Angeles, California, United States
Cedars-Sinai Medical Center (Site #: 71026)
🇺🇸Los Angeles, California, United States
Mattel Children's Hospital, UCLA (Site #: 71012)
🇺🇸Los Angeles, California, United States
UCSD Rady Children's Hospital (Site #: 71037)
🇺🇸San Diego, California, United States
Children's Hospital of Colorado (Site #: 71019)
🇺🇸Aurora, Colorado, United States
Nemours Children's Health (Site #: 71042)
🇺🇸Wilmington, Delaware, United States
Children's National Medical Center (Site #: 71039)
🇺🇸Washington, District of Columbia, United States
Ann and Robert H. Lurie Children's Hospital of Chicago (Site #: 71016)
🇺🇸Chicago, Illinois, United States
Johns Hopkins Children's Center (Site #: 71025)
🇺🇸Baltimore, Maryland, United States
Boston Children's Hospital (Site #: 71001)
🇺🇸Boston, Massachusetts, United States
Helen DeVos Children's Hospital (Site #: 71035)
🇺🇸Grand Rapids, Michigan, United States
Washington University/St. Louis Children's Hospital (Site #: 71006)
🇺🇸Saint Louis, Missouri, United States
New York Medical College/Boston Children's Health Physicians
🇺🇸Westchester, New York, United States
Duke University (Site #: 71033)
🇺🇸Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center (Site #: 71017)
🇺🇸Cincinnati, Ohio, United States
Children's Hospital of Philadelphia (Site #: 71091)
🇺🇸Philadelphia, Pennsylvania, United States
UPMC Children's Hospital of Pittsburgh (Site #: 71008)
🇺🇸Pittsburgh, Pennsylvania, United States
Texas Children's Hospital (Baylor) (Site #: 71005)
🇺🇸Houston, Texas, United States
Seattle Children's Hospital (Site #: 71041)
🇺🇸Seattle, Washington, United States
British Columbia Children's Hospital (Site #: 71034)
🇨🇦Vancouver, British Columbia, Canada