Advancing Transplantation Outcomes in Children

Kidney Transplant Clinical Trial

— ADVANTage  

Official title:

Advancing Transplantation Outcomes in Children (CTOT-41)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06055608
• Other study ID #: DAIT CTOT-41
• Status: Recruiting
• Phase: Phase 2
• Start date: May 22, 2024
• Est. completion date: November 1, 2028

Study information

• Verified date: June 2024
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. The duration of the study from time of transplant to the primary endpoint is 12-24 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: November 1, 2028
• Est. primary completion date: November 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years to 20 Years

Eligibility

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 or historical anti-HLA antibody to the donor at the time of transplant within 30 days 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

Related Conditions & MeSH terms

• Kidney Transplant

Intervention

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

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

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
• 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
• 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
• 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

Locations

Country	Name	City	State
Canada	British Columbia Children's Hospital (Site #: 71034)	Vancouver	British Columbia
United States	Children's Hospital of Colorado (Site #: 71019)	Aurora	Colorado
United States	Johns Hopkins Children's Center (Site #: 71025)	Baltimore	Maryland
United States	University of Alabama at Birmingham (Site # 71038)	Birmingham	Alabama
United States	Boston Children's Hospital (Site #: 71001)	Boston	Massachusetts
United States	Ann and Robert H. Lurie Children's Hospital of Chicago (Site #: 71016)	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center (Site #: 71017)	Cincinnati	Ohio
United States	Duke University (Site #: 71033)	Durham	North Carolina
United States	Helen DeVos Children's Hospital (Site #: 71035)	Grand Rapids	Michigan
United States	Texas Children's Hospital (Baylor) (Site #: 71005)	Houston	Texas
United States	Cedars-Sinai Medical Center (Site #: 71026)	Los Angeles	California
United States	Children's Hospital of Los Angeles (Site #: 71036)	Los Angeles	California
United States	Mattel Children's Hospital, UCLA (Site #: 71036)	Los Angeles	California
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	Washington University/St. Louis Children's Hospital (Site #: 71006)	Saint Louis	Missouri
United States	UCSD Rady Children's Hospital (Site #: 71012)	San Diego	California
United States	Seattle Children's Hospital (Site #: 71041)	Seattle	Washington
United States	Children's National Hospital (Site #: 71039)	Washington	District of Columbia
United States	Nemours Children's Health (Site #: 71042)	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Incidence of clinical biopsy proven allograft rejection (central lab)		Within 2 years post-transplant
Secondary	Time to development of clinical biopsy proven allograft rejection (central lab)		Within 2 years post-transplant
Secondary	Incidence of subclinical biopsy proven allograft rejection (central lab)		Within 2 years post-transplant
Secondary	Time to development of subclinical biopsy proven allograft rejection (central lab)		Within 2 years post-transplant
Secondary	Incidence of Post-Transplant Lymphoproliferative Disease (PTLD)		Within 2 years post-transplant
Secondary	Time to development of the PTLD		Within 2 years post-transplant
Secondary	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
Secondary	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