A Study to Evaluate the Benefits and Risks of Conversion of Existing Adolescent Kidney Transplant Recipients Aged 12 to <18 Years to a Belatacept-based Immunosuppressive Regimen as Compared to Continuation of a Calcineurin Inhibitor-based Regimen, and Their Adherence to Immunosuppressive Medications
- Conditions
- Renal Allograft Recipients
- Interventions
- Registration Number
- NCT04877288
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to evaluate the benefits and risks of conversion of existing adolescent kidney allograft recipients aged 12 to less than 18 years of age to a belatacept-based immunosuppressive regimen as compared to continuation of a calcineurin inhibitor-based regimen and their adherence to immunosuppressive medications.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 102
- Male and female adolescents 12 to less than 18 years of age
- Recipients of a renal allograft from a living or deceased donor transplanted at least 6 calendar months prior to enrollment
- Receiving a stable regimen of a calcineurin inhibitor (CNI), with mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium/mycophenolate mofetil (EC-MPS/MPA), with or without daily corticosteroids for ≥ 30 days prior to randomization
- Clinically stable renal function during the 12-week period prior to screening, in the opinion of the investigator and based on protocol-defined criteria for proteinuria and estimated glomerular filtration rate (eGFR)
- Serologic evidence of past exposure to Epstein-Barr virus (EBV) and current absence of EBV DNA replication at or prior to renal transplantation and during the Screening period
- Completion of an initial course of SARS-CoV-2 vaccination per local standard of care, a minimum of 6 weeks prior to enrollment
- Recipients with EBV serostatus negative or unknown at screening or at transplant
- Treatment for biopsy-proven acute rejection (BPAR) of any degree of severity within 6 calendar months prior to enrollment
- Biopsy-confirmed antibody-mediated acute rejection at any time with the current allograft
- Banff 97 grade IIA or higher acute cellular rejection (or equivalent), or treatment with plasmapheresis or rituximab for any acute rejection at any time with the current allograft
- Current evidence or past history of active or inadequately treated latent tuberculosis (TB) infection
- Previously treated with belatacept or previously enrolled in a belatacept trial with their present allograft
Other inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2: Continue calcineurin inhibitor-based regimen Enteric Coated Mycophenolate Sodium - Arm 1: Conversion from a CNI- to belatacept-based regimen after a period of overlap Belatacept Conversion followed by tapering and discontinuation of the calcineurin inhibitor (CNI) Arm 2: Continue calcineurin inhibitor-based regimen Corticosteroids - Arm 1: Conversion from a CNI- to belatacept-based regimen after a period of overlap Tacrolimus Conversion followed by tapering and discontinuation of the calcineurin inhibitor (CNI) Arm 1: Conversion from a CNI- to belatacept-based regimen after a period of overlap Cyclosporine A Conversion followed by tapering and discontinuation of the calcineurin inhibitor (CNI) Arm 1: Conversion from a CNI- to belatacept-based regimen after a period of overlap Enteric Coated Mycophenolate Sodium Conversion followed by tapering and discontinuation of the calcineurin inhibitor (CNI) Arm 1: Conversion from a CNI- to belatacept-based regimen after a period of overlap Corticosteroids Conversion followed by tapering and discontinuation of the calcineurin inhibitor (CNI) Arm 2: Continue calcineurin inhibitor-based regimen Tacrolimus - Arm 2: Continue calcineurin inhibitor-based regimen Cyclosporine A - Arm 2: Continue calcineurin inhibitor-based regimen Mycophenolate Mofetil - Arm 1: Conversion from a CNI- to belatacept-based regimen after a period of overlap Mycophenolate Mofetil Conversion followed by tapering and discontinuation of the calcineurin inhibitor (CNI)
- Primary Outcome Measures
Name Time Method Proportion of participants who survive with a functional graft with estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 (updated Schwartz formula) at 24 months post-randomization 24 months
- Secondary Outcome Measures
Name Time Method Intensity of antihypertensive drug therapy, defined as the total number of medications used to maintain BP control Up to 24 months Monitoring of safety laboratory parameters over time: Mean fasting lipid profiles Up to 24 months Monitoring of safety laboratory parameters over time: Fasting blood glucose concentrations Up to 24 months Monitoring of safety laboratory parameters over time: Hemoglobin A1c concentrations Up to 24 months Participant and graft survival: Proportion of participants who survive with a functioning graft 6, 12 and 24 months Participant and graft survival: Proportion of participants who survive 6, 12, and 24 months Participant and graft survival: Proportion of participants who experience death-censored graft loss 6, 12, and 24 months Acute rejection: Incidence of clinically suspected biopsy-proven acute rejection (BPAR) 3, 6, 12, and 24 months Acute rejection: Severity of clinically suspected, biopsy confirmed rejection as determined by locally and centrally reviewed histopathology 3, 6, 12, and 24 months Renal function as assessed by: Serum creatinine concentration Up to 24 months Renal function as assessed by: Estimated GFR (eGFR per updated Schwartz combined equation) Up to 24 months Renal function as assessed by: eGFR per updated bedside Schwartz approximating equation Up to 24 months Renal function as assessed by: eGFR per Full Age Spectrum (FAS) equation of Potell et al Up to 24 months Renal function as assessed by: eGFR per age and sex-dependent equation of Pierce et al Up to 24 Months Proteinuria, as assessed by urinary protein:creatinine ratio (UPCR), as determined from single-voided urine specimens Up to 24 months Slope of change in eGFR over time, as assessed by baseline-adjusted mean eGFR determinations at protocol-specified study visits Up to 24 months Adherence to immunosuppressive medications as assessed by variation in calcineurin inhibitor pre-dose whole blood concentrations by summaries over time of monitored adherence to orally administered immunosuppressive medications up to 24 months Adherence to immunosuppressive medications, as assessed by: Variations in pre-dose concentrations of calcineurin inhibitor in whole blood Up to 24 months Adherence to immunosuppressive medications, as assessed by: 7-day recall of missed and late doses of each orally administered immuno-suppressive medication at protocol-specified study visits Up to 24 months Adherence to immunosuppressive medications, as assessed by: Monitoring of compliance with monthly belatacept infusions Up to 24 months Adherence to immunosuppressive medications, as assessed by: Periodic review of parents' and patients' perceived barriers to adherence to the prescribed immunosuppressive medications regimen Up to 24 months Mean blood pressure over time Up to 24 months Mean blood pressure changes from baseline over time Up to 24 months Donor Specific antibodies (DSA): Proportion of participants with pre-existing anti-human leukocyte antigen (HLA) DSAs at baseline and with de novo anti-HLA DSA post-randomization 6, 12, and 24 months Immunogenicity of belatacept as determined by the proportion of participants with detectable serum anti-belatacept antibodies 6, 12, and 24 months Belatacept pre-dose (C0) serum concentrations Up to 24 months Mean percent belatacept CD86 receptor occupancy Baseline Post-randomization changes from baseline percent belatacept CD86 receptor occupancy 6, 12, and 24 months Safety and tolerability of belatacept following conversion: Incidence of Adverse Events (AEs) up to 24 months Safety and tolerability of belatacept following conversion: Incidence of Serious Adverse Events (SAEs) Up to 24 months Safety and tolerability of belatacept following conversion: Incidence of laboratory marked abnormalities Up to 24 months Proportion of participants within each stage of the Tanner staging scale Up to 24 months The Tanner scale is a measure of pubertal development (sexual maturation) in children and adolescents with components described for each sex, rated separately on a scale of stage one to stage five, with 1 for preadolescent and 5 for mature/adult
Linear growth (height) Up to 24 months
Trial Locations
- Locations (37)
Local Institution - 0022
🇺🇸Hollywood, Florida, United States
Local Institution - 0045
🇺🇸Miami, Florida, United States
Local Institution - 0049
🇺🇸Atlanta, Georgia, United States
Local Institution - 0033
🇺🇸Chicago, Illinois, United States
Local Institution - 0017
🇺🇸Baltimore, Maryland, United States
Local Institution - 0044
🇺🇸Boston, Massachusetts, United States
Local Institution - 0043
🇺🇸Saint Louis, Missouri, United States
Local Institution - 0024
🇺🇸Durham, North Carolina, United States
Local Institution - 0025
🇺🇸Cincinnati, Ohio, United States
Local Institution - 0048
🇺🇸Cleveland, Ohio, United States
Local Institution - 0052
🇺🇸Portland, Oregon, United States
Local Institution - 0038
🇺🇸Seattle, Washington, United States
Local Institution - 0001
🇪🇸Barcelona, Spain
Local Institution - 0012
🇪🇸Rivas Vaciamadrid, Spain
Local Institution - 0003
🇪🇸Sevilla, Spain
Local Institution - 0008
🇬🇧Manchester, United Kingdom
Local Institution - 0009
🇬🇧Nottingham, United Kingdom
Local Institution - 0042
🇺🇸Birmingham, Alabama, United States
Local Institution - 0041
🇺🇸Los Angeles, California, United States
Local Institution - 0014
🇺🇸Washington, District of Columbia, United States
Emma Children (AMC)
🇳🇱Amsterdam, Netherlands
Local Institution - 0061
🇳🇴Oslo, Norway
Ospedale Regina Margherita-S.C Nefrologia, Dialisi e Trapianto Renale
🇮🇹Torino, Italy
Local Institution - 0060
🇦🇷ABB, Ciudad Autónoma De Buenos Aires, Argentina
UZ Gent-Paediatric Nephrology and Rheumatology Department
🇧🇪Gent, Belgium
Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu
🇫🇷Nantes, Loire-Atlantique, France
Bordeaux University Hospital - Pellegrin-Pediatrics
🇫🇷Bordeaux, France
Hospices Civils de Lyon - Hôpital Femme Mère Enfant-néphrologie pédiatrique
🇫🇷Bron, France
Hopital De La Timone
🇫🇷Marseille, France
Hopital Necker
🇫🇷Paris, France
Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Robert Debre - Centre Hospitalo Universita
🇫🇷Paris, France
Universitaetsklinikum Essen
🇩🇪Essen, Nordrhein-Westfalen, Germany
Local Institution - 0011
🇩🇪Hamburg, Germany
Local Institution - 0026
🇩🇪Heidelberg, Germany
Local Institution - 0010
🇩🇪Köln, Germany
Local Institution - 0059
🇮🇹Genova, Liguria, Italy
Local Institution - 0030
🇮🇹Milano, Italy