Advancing Transplantation Outcomes in Children (CTOT-41)
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 200
- Locations
- 39
- Primary Endpoint
- 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)
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 13 Years to 20 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •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.
Exclusion Criteria
- •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)
- •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
Arms & Interventions
(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)
Intervention: Sirolimus (Drug)
(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)
Intervention: Belatacept (Biological)
(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)
Intervention: Tacrolimus (Group1) (Drug)
(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)
Intervention: Anti-Thymocyte Globulin (ATG) (Drug)
(Group 2): Tacrolimus + Mycophenolate Mofetil (MMF) group
Participants in this group will receive anti-thymocyte globulin (ATG) + steroid taper + tacrolimus + MMF
Intervention: Mycophenolate Mofetil (Drug)
(Group 2): Tacrolimus + Mycophenolate Mofetil (MMF) group
Participants in this group will receive anti-thymocyte globulin (ATG) + steroid taper + tacrolimus + MMF
Intervention: Anti-Thymocyte Globulin (ATG) (Drug)
(Group 2): Tacrolimus + Mycophenolate Mofetil (MMF) group
Participants in this group will receive anti-thymocyte globulin (ATG) + steroid taper + tacrolimus + MMF
Intervention: Tacrolimus (Group 2) (Drug)
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Time to development of clinical biopsy proven allograft rejection (central lab)(Within 96 weeks post-transplant)
- Time to development of the PTLD(Within 96 weeks post-transplant)
- Incidence of clinical biopsy proven allograft rejection (central lab)(Within 96 weeks post-transplant)
- Incidence of subclinical biopsy proven allograft rejection (central lab)(Within 96 weeks post-transplant)
- Time to development of subclinical biopsy proven allograft rejection (central lab)(Within 96 weeks post-transplant)
- Incidence of Post-Transplant Lymphoproliferative Disease (PTLD)(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(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(Within 96 weeks post-transplant)