ADVANTage: Advancing Transplantation Outcomes in Children

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06055608
• Collaborator: (none)
• Enrollment: 200
• Locations: 18
• Arms: 2
• Anticipated Duration (Months): 60
• Patients Per Site: 11.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplant	Drug: Sirolimus; Biological: Belatacept; Drug: Mycophenolate Mofetil; Drug: Tacrolimus (Group1); Drug: Anti-Thymocyte Globulin (ATG); Drug: Tacrolimus (Group 2)	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Advancing Transplantation Outcomes in Children (CTOT-41)
• Anticipated Study Start Date: Nov 1, 2023
• Anticipated Primary Completion Date: Nov 1, 2028
• Anticipated Study Completion Date: Nov 1, 2028

Arms and Interventions

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: AY 22-989 Rapamune Rapamycin ; 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: FK-506 FR-900506 Prograf ; 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: 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: 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: 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: FK-506 FR-900506 Prograf

Outcome Measures

Primary Outcome Measures

1. 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

1. Incidence of clinical biopsy proven allograft rejection (central lab) [Within 2 years post-transplant]

2. Time to development of clinical biopsy proven allograft rejection (central lab) [Within 2 years post-transplant]

3. Incidence of subclinical biopsy proven allograft rejection (central lab) [Within 2 years post-transplant]

4. Time to development of subclinical biopsy proven allograft rejection (central lab) [Within 2 years post-transplant]

5. Incidence of Post-Transplant Lymphoproliferative Disease (PTLD) [Within 2 years post-transplant]

6. Time to development of the PTLD [Within 2 years post-transplant]

7. 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]

8. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years to 20 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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) at time of enrollment

5. If a female participant of childbearing potential, a negative pregnancy test within 48 hours of enrollment

6. If participant has reproductive potential, agrees to use Food and Drug Administration (FDA) approved methods of birth control for the duration of the study

7. 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

8. 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. Current or historical anti-HLA antibody to the donor

5. Peak calculated Panel Reactive Antibody (cPRA) greater than 80 percent

6. Receipt of any licensed or investigational live attenuated vaccine(s) within 4 weeks of enrollment

7. Prior history of organ transplantation

8. Active systemic autoimmune disease at time of enrollment

9. Idiopathic Focal Segmental Glomerulosclerosis (FSGS), Membranoproliferative Glomerulonephritis (MPGN), C3 glomerulopathy, or atypical Hemolytic Uremic Syndrome (HUS) suspected at risk for recurrence

10. Use of immunosuppressants, biologics (including IVIG), chronic corticosteroids or investigational drug(s) within 8 weeks of enrollment

11. Known bleeding disorder

12. Platelet count < 75,000 cells/microliters within 3 months of enrollment

13. History of inherited hypercoagulability requiring therapy more than aspirin

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 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. 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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama School of Medicine: Pediatric Transplantation	Birmingham	Alabama	United States	35233
2	Children's Hospital Los Angeles: Pediatric Transplantation	Los Angeles	California	United States	90027
3	Cedars Sinai Medical Center: Pediatric Transplantation	Los Angeles	California	United States	90048
4	Ronald Reagan UCLA Medical Center: Pediatric Transplantation	Los Angeles	California	United States	90095
5	University of California San Diego, Rady Children's Hospital: Pediatric Transplantation	San Diego	California	United States	92123
6	Children's Hospital Colorado: Pediatric Transplantation	Aurora	Colorado	United States	80045
7	Children's National Medical Center: Pediatric Transplantation	Washington	District of Columbia	United States	20010
8	Ann and Robert H. Lurie Children's Hospital of Chicago: Pediatric Transplantation	Chicago	Illinois	United States	60611
9	Boston Children's Hospital: Pediatric Transplantation	Boston	Massachusetts	United States	02215
10	Helen DeVos Children's Hospital: Pediatric Transplantation	Grand Rapids	Michigan	United States	49503
11	St. Louis Children's Hospital: Pediatric Transplantation	Saint Louis	Missouri	United States	63110
12	Duke University Medical Center: Department of Pediatrics	Durham	North Carolina	United States	27710
13	Cincinnati Children's Hospital Medical Center: Pediatric Transplantation	Cincinnati	Ohio	United States	45229
14	Children's Hospital of Philadelphia: Pediatric Transplantation	Philadelphia	Pennsylvania	United States	19104
15	Children's Hospital of Pittsburgh: Pediatric Transplantation	Pittsburgh	Pennsylvania	United States	15224
16	Texas Children's Hospital: Pediatric Transplantation	Houston	Texas	United States	77030
17	Seattle Children's Hospital: Pediatric Transplantation	Seattle	Washington	United States	98105
18	British Columbia Children's Hospital: Pediatric Transplantation	Vancouver		Canada

Sponsors and Collaborators

• 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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT06055608
• Other Study ID Numbers: DAIT CTOT-41
• First Posted: Sep 28, 2023
• Last Update Posted: Sep 28, 2023
• Last Verified: Sep 1, 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): kidney transplant; belatacept; sirolimus
• Additional relevant MeSH terms: Mycophenolic Acid; Sirolimus; Abatacept; Tacrolimus; Antilymphocyte Serum

Study Results

No Results Posted as of Sep 28, 2023