Advancing Transplantation Outcomes in Children (ADVANTage)

May 19, 2026 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Advancing Transplantation Outcomes in Children (CTOT-41)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • University of Alabama at Birmingham (Site # 71038)
        • Contact:
    • California
      • Los Angeles, California, United States, 90027
        • Not yet recruiting
        • Children's Hospital of Los Angeles (Site #: 71036)
        • Contact:
      • Los Angeles, California, United States, 90095
        • Recruiting
        • Mattel Children's Hospital, UCLA (Site #: 71012)
        • Contact:
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars-Sinai Medical Center (Site #: 71026)
        • Contact:
      • San Diego, California, United States, 92123
        • Recruiting
        • UCSD Rady Children's Hospital (Site #: 71037)
        • Contact:
    • Colorado
      • Aurora, Colorado, United States, 80045
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Recruiting
        • Nemours Children's Health (Site #: 71042)
        • Contact:
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Recruiting
        • Children's National Medical Center (Site #: 71039)
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Ann and Robert H. Lurie Children's Hospital of Chicago (Site #: 71016)
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins Children's Center (Site #: 71025)
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University/St. Louis Children's Hospital (Site #: 71006)
        • Contact:
    • New York
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University (Site #: 71033)
        • Contact:
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Children's Hospital Medical Center (Site #: 71017)
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philadelphia (Site #: 71091)
        • Contact:
      • Pittsburgh, Pennsylvania, United States, 15224
        • Recruiting
        • UPMC Children's Hospital of Pittsburgh (Site #: 71008)
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Texas Children's Hospital (Baylor) (Site #: 71005)
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98105

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

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 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 45 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 at any point in time
  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 within 8 weeks of randomization, except in the case of planned transplant standard of care
  11. Treatment with biologics (including IVIG) within 8 weeks of randomization

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • Rapamycin
  • Rapamune
  • AY 22-989
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:
  • Prograf
  • FK-506
  • FR-900506
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: 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: 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: 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:
  • Prograf
  • FK-506
  • FR-900506

What is the study measuring?

Primary Outcome Measures

Outcome 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)
Time Frame: At 96 weeks post-transplant
At 96 weeks post-transplant

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence of clinical biopsy proven allograft rejection (central lab)
Time Frame: Within 96 weeks post-transplant
Within 96 weeks post-transplant
Time to development of clinical biopsy proven allograft rejection (central lab)
Time Frame: Within 96 weeks post-transplant
Within 96 weeks post-transplant
Incidence of subclinical biopsy proven allograft rejection (central lab)
Time Frame: Within 96 weeks post-transplant
Within 96 weeks post-transplant
Time to development of subclinical biopsy proven allograft rejection (central lab)
Time Frame: Within 96 weeks post-transplant
Within 96 weeks post-transplant
Incidence of Post-Transplant Lymphoproliferative Disease (PTLD)
Time Frame: Within 96 weeks post-transplant
Within 96 weeks post-transplant
Time to development of the PTLD
Time Frame: Within 96 weeks post-transplant
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
Time Frame: Within 96 weeks post-transplant
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
Time Frame: Within 96 weeks post-transplant
Within 96 weeks post-transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: David Briscoe, MD, Boston Children's Hospital: Pediatric Transplantation
  • Study Chair: Eileen Chambers, MD, Duke University Medical Center: Department of Pediatrics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 22, 2024

Primary Completion (Estimated)

June 30, 2028

Study Completion (Estimated)

June 30, 2028

Study Registration Dates

First Submitted

September 20, 2023

First Submitted That Met QC Criteria

September 20, 2023

First Posted (Actual)

September 28, 2023

Study Record Updates

Last Update Posted (Actual)

May 20, 2026

Last Update Submitted That Met QC Criteria

May 19, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DAIT CTOT-41

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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