Clinical trial NCT06055608: Advancing Transplantation Outcomes in Children
Official title: Advancing Transplantation Outcomes in Children (CTOT-41)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Kidney Transplant
Keywords: kidney transplant
belatacept
sirolimus
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2023-09-28
Enrollment: 200
Sex: ALL
Minimum age (years): 13
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: At 2 years post-transplant
Secondary outcomes:
measure: Incidence of clinical biopsy proven allograft rejection (central lab)
timeFrame: Within 2 years post-transplant
measure: Time to development of clinical biopsy proven allograft rejection (central lab)
timeFrame: Within 2 years post-transplant
measure: Incidence of subclinical biopsy proven allograft rejection (central lab)
timeFrame: Within 2 years post-transplant
measure: Time to development of subclinical biopsy proven allograft rejection (central lab)
timeFrame: Within 2 years post-transplant
measure: Incidence of Post-Transplant Lymphoproliferative Disease (PTLD)
timeFrame: Within 2 years post-transplant
measure: Time to development of the PTLD
timeFrame: Within 2 years post-transplant
measure: Incidence of Grade 3 and above opportunistic infections bacterial, viral, fungal, pneumocystis pneumonia, or parasitic infections assessed as a composite
timeFrame: Within 2 years post-transplant
measure: Time to development of Grade 3 and above opportunistic infections bacterial, viral, fungal, pneumocystis pneumonia, or parasitic infections assessed as a composite
timeFrame: Within 2 years post-transplant
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham (Site # 71038)
state: Alabama
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles (Site #: 71036)
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center (Site #: 71026)
state: California
city: Los Angeles
country: United States
facility: Mattel Children's Hospital, UCLA (Site #: 71012)
state: California
city: San Diego
country: United States
facility: UCSD Rady Children's Hospital (Site #: 71037)
state: California
city: Aurora
country: United States
facility: Children's Hospital of Colorado (Site #: 71019)
state: Colorado
city: Wilmington
country: United States
facility: Nemours Children's Health (Site #: 71042)
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center (Site #: 71039)
state: District of Columbia
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital of Chicago (Site #: 71016)
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Children's Center (Site #: 71025)
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital (Site #: 71001)
state: Massachusetts
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital (Site #: 71035)
state: Michigan
city: Saint Louis
country: United States
facility: Washington University/St. Louis Children's Hospital (Site #: 71006)
state: Missouri
city: Westchester
country: United States
facility: New York Medical College/Boston Children's Health Physicians
state: New York
city: Durham
country: United States
facility: Duke University (Site #: 71033)
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center (Site #: 71017)
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia (Site #: 71091)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh (Site #: 71008)
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital (Baylor) (Site #: 71005)
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital (Site #: 71041)
state: Washington
Study officials:
affiliation: Boston Children's Hospital: Pediatric Transplantation
name: David Briscoe, MD
role: STUDY_CHAIR
affiliation: Duke University Medical Center: Department of Pediatrics
name: Eileen Chambers, MD
role: STUDY_CHAIR
References: