Kidney TransplantPhase 2ADVANTageNCT06055608
Advancing Transplantation Outcomes in Children
A Phase 2 study testing Sirolimus, Belatacept and Mycophenolate Mofetil in people with Kidney Transplant, run by National Institute of Allergy and Infectious Diseases (NIAID) at 21 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 13 to 20 years
- Conditions the study is for
- Kidney Transplant
- What is being tested?
- Sirolimus, Belatacept and Mycophenolate Mofetil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 21 sitesin 2 countries
- Study dates
- 22 May 2024to 30 Jun 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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 living or 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 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
- If a female participant of childbearing potential, a negative pregnancy test prior to conducting any study procedures
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- 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.
Who cannot join
- 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
- Listed for multi-organ transplant (e.g. heart- kidney, liver-kidney, multivisceral- kidney, lung- kidney)
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- 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
- Panel Reactive Antibody (cPRA) greater than 80 percent
- 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.
- 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.
- 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 45 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 at any point in time
- 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 within 8 weeks of randomization, except in the case of planned transplant standard of care
- Treatment with biologics (including IVIG) within 8 weeks of randomization
Trial locations and contacts
21 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
21 sites in 2 countries
United States20 sites, 20 recruiting
- Recruiting
Children's Hospital of Colorado (Site #: 71019)
Aurora, Colorado, 80045
Claire Giachino, 720-770-0107, Claire.Giachino@childrenscolorado.org
- Recruiting
Johns Hopkins Children's Center (Site #: 71025)
Baltimore, Maryland, 21287
Ryan Hutson, 443-287-3214, rhutson1@jhmi.edu
- Recruiting
University of Alabama at Birmingham (Site # 71038)
Birmingham, Alabama, 35233
Scott House, 205-638-9781, whouse@uabmc.edu
- Recruiting
Boston Children's Hospital (Site #: 71001)
Boston, Massachusetts, 02215
Emily Toal, MPH, 617-919-6535, emily.toal@childrens.harvard.edu
- Recruiting
Ann and Robert H. Lurie Children's Hospital of Chicago (Site #: 71016)
Chicago, Illinois, 60611
Petula Grant, 312-227-7401, pgrant@luriechildrens.org
- Recruiting
Cincinnati Children's Hospital Medical Center (Site #: 71017)
Cincinnati, Ohio, 45229
Nina Kanis, 513-803-1053, Nina.Kanis@cchmc.org
- Recruiting
Duke University (Site #: 71033)
Durham, North Carolina, 27710
Hannah Joy Porter, 919-684-0356, hanajoy.porter@duke.edu
- Recruiting
Helen DeVos Children's Hospital (Site #: 71035)
Grand Rapids, Michigan, 49503
Lena Sanfilippo, 616-391-4305, lena.sanfilippo@corewellhealth.org
- Recruiting
Texas Children's Hospital (Baylor) (Site #: 71005)
Houston, Texas, 77030
Irina Dinu, 832-824-3388, irina.dinu@bcm.edu
- Not yet recruiting
Children's Hospital of Los Angeles (Site #: 71036)
Los Angeles, California, 90027
Ariana Teame, 1-323-419-2774, ateame@chla.usc.edu
- Recruiting
Cedars-Sinai Medical Center (Site #: 71026)
Los Angeles, California, 90048
Kelly Kirshner, 310-825-0922, Kelly.kirshner@cshs.org
- Recruiting
Mattel Children's Hospital, UCLA (Site #: 71012)
Los Angeles, California, 90095
Serena Ridge, 1-310-968-4225, SRidge@mednet.ucla.edu
- Recruiting
Children's Hospital of Philadelphia (Site #: 71091)
Philadelphia, Pennsylvania, 19104
Annie Chung, 267-425-3934, Chunga@chop.edu
- Recruiting
UPMC Children's Hospital of Pittsburgh (Site #: 71008)
Pittsburgh, Pennsylvania, 15224
Vibha Chauhan, 412-692-6739, vibha.chauhan@chp.edu
- Recruiting
UCSD Rady Children's Hospital (Site #: 71037)
San Diego, California, 92123
Kristin Zeeb, 858-966-1700 ext. 221657, kzeeb@health.ucsd.edu
- Recruiting
Seattle Children's Hospital (Site #: 71041)
Seattle, Washington, 98105
Megan Kelton, 206-987-5539, megan.kelton@seattlechildrens.org
- Recruiting
Washington University/St. Louis Children's Hospital (Site #: 71006)
St Louis, Missouri, 63110
Lujain Jaza, 314-747-1846, jaza@wustl.edu
- Recruiting
Children's National Medical Center (Site #: 71039)
Washington D.C., District of Columbia, 20010
Mirian Naybor, 202-476-6659, mnaybor@childrensnational.org
- Not yet recruiting
New York Medical College/Boston Children's Health Physicians
Westchester, New York, 10461
Armando Ramirez, (914) 504-0152, Armando_Ramirez@bchphysicians.org
Zachary Messer, Zachary_Messer@bchphysicians.org
- Recruiting
Nemours Children's Health (Site #: 71042)
Wilmington, Delaware, 19803
Aiyana Bullock, 302-274-9333, aiyana.bullock@nemours.org
Canada1 site, 1 recruiting
- Recruiting
British Columbia Children's Hospital (Site #: 71034)
Vancouver, British Columbia, V5Z 4H4
Mattias Hui, 1-604-875-2000, mattias.hui@bcchr.ca
About this study
Official title: 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.
- Conditions
- Kidney Transplant
- Being tested
- Sirolimus, Belatacept, Mycophenolate Mofetil, Tacrolimus (Group1), Anti-Thymocyte Globulin (ATG)
- Keywords
- kidney transplant, belatacept, sirolimus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called AY 22-989, Rapamune, Rapamycin
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
BelataceptBiological
Also called Nulojix
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
Also called CellCept, MMF
Mycophenolate Mofetil-MMF will be initiated at 600 mg/m^2 BID until tacrolimus is at therapeutic levels, then 450 mg/m^2 BID
Tacrolimus (Group1)Drug
Also called FK-506, FR-900506, Prograf
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
Anti-Thymocyte Globulin (ATG)Drug
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
Tacrolimus (Group 2)Drug
Also called FK-506, FR-900506, Prograf
Participants will receive Prograf® (tacrolimus), or generic, initiated at 0.1 mg/kg BID within 48 hours of transplantation to attain target trough levels
| Study group | Role | What they receive |
|---|---|---|
| (Group 1): Belatacept+Sirolimus group | Experimental | 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) Receives: Drug: Sirolimus; Biological: Belatacept; Drug: Tacrolimus (Group1); Drug: Anti-Thymocyte Globulin (ATG) |
| (Group 2): Tacrolimus + Mycophenolate Mofetil (MMF) group | Active comparator | Participants in this group will receive anti-thymocyte globulin (ATG) + steroid taper + tacrolimus + MMF Receives: Drug: Mycophenolate Mofetil; Drug: Anti-Thymocyte Globulin (ATG); Drug: Tacrolimus (Group 2) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: At 96 weeks post-transplant
Secondary outcomes (8)
Incidence of clinical biopsy proven allograft rejection (central lab)
Measured: Within 96 weeks post-transplant
Time to development of clinical biopsy proven allograft rejection (central lab)
Measured: Within 96 weeks post-transplant
Incidence of subclinical biopsy proven allograft rejection (central lab)
Measured: Within 96 weeks post-transplant
Time to development of subclinical biopsy proven allograft rejection (central lab)
Measured: Within 96 weeks post-transplant
Incidence of Post-Transplant Lymphoproliferative Disease (PTLD)
Measured: Within 96 weeks post-transplant
Time to development of the PTLD
Measured: 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
Measured: 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
Measured: Within 96 weeks post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2023
- Study start22 May 2024
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney TransplantStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- David Briscoe, MD, Study chair, Boston Children's Hospital: Pediatric TransplantationEileen Chambers, MD, Study chair, Duke University Medical Center: Department of Pediatrics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06055608
- Sponsor's protocol ID
- DAIT CTOT-41
- Acronym
- ADVANTage
- Status last verified
- Oct 2026
- First submitted
- 20 Sep 2023
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No