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

Phase 3RecruitingNCT04877288

Bristol-Myers Squibb102 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

102

Conditions

Renal Allograft Recipients

Interventions

BelataceptBIOLOGICAL

Specified dose on specified days

Eligibility

Sex: ALLMin age: 12 YearsMax age: 17 Years

Medical Language ↔ Plain English

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

Locations (38)

Local Institution - 0042

Birmingham, Alabama, United States

WITHDRAWN

Local Institution - 0041

Los Angeles, California, United States

WITHDRAWN

Local Institution - 0014

Washington D.C., District of Columbia, United States

WITHDRAWN

Local Institution - 0022

Hollywood, Florida, United States

WITHDRAWN

Outcomes

Primary Outcomes

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

Time frame: 24 months

Secondary Outcomes

Participant and graft survival: Proportion of participants who survive with a functioning graft

Time frame: 6, 12 and 24 months

Participant and graft survival: Proportion of participants who survive

Time frame: 6, 12, and 24 months

Participant and graft survival: Proportion of participants who experience death-censored graft loss

Time frame: 6, 12, and 24 months

Acute rejection: Incidence of clinically suspected biopsy-proven acute rejection (BPAR)

Time frame: 3, 6, 12, and 24 months

Acute rejection: Severity of clinically suspected, biopsy confirmed rejection as determined by locally and centrally reviewed histopathology

Time frame: 3, 6, 12, and 24 months

Renal function as assessed by: Serum creatinine concentration

Time frame: Up to 24 months

Renal function as assessed by: Estimated GFR (eGFR per updated Schwartz combined equation)

Time frame: Up to 24 months

Renal function as assessed by: eGFR per updated bedside Schwartz approximating equation

Time frame: Up to 24 months

Renal function as assessed by: eGFR per Full Age Spectrum (FAS) equation of Potell et al

Time frame: Up to 24 months

Renal function as assessed by: eGFR per age and sex-dependent equation of Pierce et al

Time frame: Up to 24 Months

Proteinuria, as assessed by urinary protein:creatinine ratio (UPCR), as determined from single-voided urine specimens

Time frame: Up to 24 months

Slope of change in eGFR over time, as assessed by baseline-adjusted mean eGFR determinations at protocol-specified study visits

Time frame: 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

Time frame: up to 24 months

Adherence to immunosuppressive medications, as assessed by: Variations in pre-dose concentrations of calcineurin inhibitor in whole blood

Time frame: 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

Time frame: Up to 24 months

Adherence to immunosuppressive medications, as assessed by: Monitoring of compliance with monthly belatacept infusions

Time frame: 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

Time frame: Up to 24 months

Mean blood pressure over time

Time frame: Up to 24 months

Mean blood pressure changes from baseline over time

Time frame: Up to 24 months

Intensity of antihypertensive drug therapy, defined as the total number of medications used to maintain BP control

Time frame: Up to 24 months

Monitoring of safety laboratory parameters over time: Mean fasting lipid profiles

Time frame: Up to 24 months

Monitoring of safety laboratory parameters over time: Fasting blood glucose concentrations

Time frame: Up to 24 months

Monitoring of safety laboratory parameters over time: Hemoglobin A1c concentrations

Time frame: 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

Time frame: 6, 12, and 24 months

Immunogenicity of belatacept as determined by the proportion of participants with detectable serum anti-belatacept antibodies

Time frame: 6, 12, and 24 months

Belatacept pre-dose (C0) serum concentrations

Time frame: Up to 24 months

Mean percent belatacept CD86 receptor occupancy

Time frame: Baseline

Post-randomization changes from baseline percent belatacept CD86 receptor occupancy

Time frame: 6, 12, and 24 months

Safety and tolerability of belatacept following conversion: Incidence of Adverse Events (AEs)

Time frame: up to 24 months

Safety and tolerability of belatacept following conversion: Incidence of Serious Adverse Events (SAEs)

Time frame: Up to 24 months

Safety and tolerability of belatacept following conversion: Incidence of laboratory marked abnormalities

Time frame: Up to 24 months

Proportion of participants within each stage of the Tanner staging scale

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

Time frame: Up to 24 months

Linear growth (height)

Time frame: Up to 24 months

Central Contacts

BMS Study Connect Contact Center www.BMSStudyConnect.com

CONTACT

855-907-3286 Clinical.Trials@bms.com

First line of the email MUST contain NCT # and Site #.

CONTACT