Clinical trial NCT04877288: 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
Official title: A Prospective, Open-label, Multicenter, Randomized Study to Evaluate the Benefits and Risks of Conversion of Existing Adolescent Renal 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Renal Allograft Recipients
Keywords: Acute rejection
Belatacept
Calcineurin inhibitors (cyclosporine, tacrolimus)
Conversion
Donor-specific antibodies
eGFR
Immunosuppressive regimen
Adolescent kidney transplant recipients
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2021-05-07
Enrollment: 102
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: 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
timeFrame: 24 months
Secondary outcomes:
measure: Participant and graft survival: Proportion of participants who survive with a functioning graft
timeFrame: 6, 12 and 24 months
measure: Participant and graft survival: Proportion of participants who survive
timeFrame: 6, 12, and 24 months
measure: Participant and graft survival: Proportion of participants who experience death-censored graft loss
timeFrame: 6, 12, and 24 months
measure: Acute rejection: Incidence of clinically suspected biopsy-proven acute rejection (BPAR)
timeFrame: 3, 6, 12, and 24 months
measure: Acute rejection: Severity of clinically suspected, biopsy confirmed rejection as determined by locally and centrally reviewed histopathology
timeFrame: 3, 6, 12, and 24 months
measure: Renal function as assessed by: Serum creatinine concentration
timeFrame: Up to 24 months
measure: Renal function as assessed by: Estimated GFR (eGFR per updated Schwartz combined equation)
timeFrame: Up to 24 months
measure: Renal function as assessed by: eGFR per updated bedside Schwartz approximating equation
timeFrame: Up to 24 months
measure: Renal function as assessed by: eGFR per Full Age Spectrum (FAS) equation of Potell et al
timeFrame: Up to 24 months
measure: Renal function as assessed by: eGFR per age and sex-dependent equation of Pierce et al
timeFrame: Up to 24 Months
measure: Proteinuria, as assessed by urinary protein:creatinine ratio (UPCR), as determined from single-voided urine specimens
timeFrame: Up to 24 months
measure: Slope of change in eGFR over time, as assessed by baseline-adjusted mean eGFR determinations at protocol-specified study visits
timeFrame: Up to 24 months
measure: 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
timeFrame: up to 24 months
measure: Adherence to immunosuppressive medications, as assessed by: Variations in pre-dose concentrations of calcineurin inhibitor in whole blood
timeFrame: Up to 24 months
measure: 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
timeFrame: Up to 24 months
measure: Adherence to immunosuppressive medications, as assessed by: Monitoring of compliance with monthly belatacept infusions
timeFrame: Up to 24 months
measure: Adherence to immunosuppressive medications, as assessed by: Periodic review of parents' and patients' perceived barriers to adherence to the prescribed immunosuppressive medications regimen
timeFrame: Up to 24 months
measure: Mean blood pressure over time
timeFrame: Up to 24 months
measure: Mean blood pressure changes from baseline over time
timeFrame: Up to 24 months
measure: Intensity of antihypertensive drug therapy, defined as the total number of medications used to maintain BP control
timeFrame: Up to 24 months
measure: Monitoring of safety laboratory parameters over time: Mean fasting lipid profiles
timeFrame: Up to 24 months
measure: Monitoring of safety laboratory parameters over time: Fasting blood glucose concentrations
timeFrame: Up to 24 months
measure: Monitoring of safety laboratory parameters over time: Hemoglobin A1c concentrations
timeFrame: Up to 24 months
measure: 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
timeFrame: 6, 12, and 24 months
measure: Immunogenicity of belatacept as determined by the proportion of participants with detectable serum anti-belatacept antibodies
timeFrame: 6, 12, and 24 months
measure: Belatacept pre-dose (C0) serum concentrations
timeFrame: Up to 24 months
measure: Mean percent belatacept CD86 receptor occupancy
timeFrame: Baseline
measure: Post-randomization changes from baseline percent belatacept CD86 receptor occupancy
timeFrame: 6, 12, and 24 months
measure: Safety and tolerability of belatacept following conversion: Incidence of Adverse Events (AEs)
timeFrame: up to 24 months
measure: Safety and tolerability of belatacept following conversion: Incidence of Serious Adverse Events (SAEs)
timeFrame: Up to 24 months
measure: Safety and tolerability of belatacept following conversion: Incidence of laboratory marked abnormalities
timeFrame: Up to 24 months
measure: Proportion of participants within each stage of the Tanner staging scale
timeFrame: Up to 24 months
measure: Linear growth (height)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution - 0042
state: Alabama
city: Los Angeles
country: United States
facility: Local Institution - 0041
state: California
city: Washington
country: United States
facility: Local Institution - 0014
state: District of Columbia
city: Hollywood
country: United States
facility: Local Institution - 0022
state: Florida
city: Miami
country: United States
facility: Local Institution - 0045
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 0049
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 0033
state: Illinois
city: Baltimore
country: United States
facility: Local Institution - 0017
state: Maryland
city: Boston
country: United States
facility: Local Institution - 0044
state: Massachusetts
city: Saint Louis
country: United States
facility: Local Institution - 0043
state: Missouri
city: Durham
country: United States
facility: Local Institution - 0024
state: North Carolina
city: Cincinnati
country: United States
facility: Local Institution - 0025
state: Ohio
city: Cleveland
country: United States
facility: Local Institution - 0048
state: Ohio
city: Portland
country: United States
facility: Local Institution - 0052
state: Oregon
city: Seattle
country: United States
facility: Local Institution - 0038
state: Washington
city: ABB
country: Argentina
facility: Local Institution - 0060
state: Ciudad Autónoma De Buenos Aires
city: Gent
country: Belgium
facility: UZ Gent-Paediatric Nephrology and Rheumatology Department
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu
state: Loire-Atlantique
city: Bordeaux
country: France
facility: Bordeaux University Hospital - Pellegrin-Pediatrics
city: Bron
country: France
facility: Hospices Civils de Lyon - Hôpital Femme Mère Enfant-néphrologie pédiatrique
city: Marseille
country: France
facility: Hopital De La Timone
city: Paris
country: France
facility: Hopital Necker
city: Paris
country: France
facility: Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Robert Debre - Centre Hospitalo Universita
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
state: Nordrhein-Westfalen
city: Hamburg
country: Germany
facility: Local Institution - 0011
city: Heidelberg
country: Germany
facility: Local Institution - 0026
city: Köln
country: Germany
facility: Local Institution - 0010
city: Genova
country: Italy
facility: Local Institution - 0059
state: Liguria
city: Milano
country: Italy
facility: Local Institution - 0030
city: Torino
country: Italy
facility: Ospedale Regina Margherita-S.C Nefrologia, Dialisi e Trapianto Renale
city: Amsterdam
country: Netherlands
facility: Emma Children (AMC)
city: Oslo
country: Norway
facility: Local Institution - 0061
city: Barcelona
country: Spain
facility: Local Institution - 0001
city: Rivas Vaciamadrid
country: Spain
facility: Local Institution - 0012
city: Sevilla
country: Spain
facility: Local Institution - 0003
city: Manchester
country: United Kingdom
facility: Local Institution - 0008
city: Nottingham
country: United Kingdom
facility: Local Institution - 0009
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: