Pharmacokinetics, Safety and Tolerability of Single-dose Belatacept in Adolescent Kidney Transplant Recipients

Bristol-Myers Squibb16 enrolled

Overview

The purpose of this study is to evaluate how well adolescent kidney transplant patients tolerate a single dose of belatacept they receive at least 6 months after transplant surgery, and how their body handles the drug.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Kidney Transplant

Interventions

BelataceptDRUG

Single intravenous infusion of belatacept, 7.5 mg/kg

Eligibility

Sex: ALLMin age: 12 YearsMax age: 17 Years

Medical Language ↔ Plain English

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Male and Female subjects,12-17 years old * Receiving CNI-based maintenance immunosuppression since the time of renal transplantation in accordance with local standard of care * Stable renal function, in the opinion of the investigator, with a cGFR\>45 mL/min/1.73m2 at the time of enrollment (per updated Schwartz Formula) * Adolescent Recipients of a renal allograft from a living donor or a deceased donor at least 6 months prior to enrollment * Subject must be receiving a calcineurin inhibitor (CNI)-based \[cyclosporine (CsA) \[any formulation\] or Tacrolimus (TAC)\] immunosuppressive regimen * Subject must be receiving adjunctive background maintenance immunosuppression with mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS)/mycophenolic acid (MPA) * Subjects may be receiving maintenance corticosteroids in accordance with the local standard of care * Negative Interferon Gamma Release Assay (IGRA) such as QuantiFERON-TB Gold test or T-Spot-TB * FOCBP must have negative serum or urine pregnancy test within 24 hrs prior to start of study medication * Subject must have stable estimated glomerular filtration rate (GFR) ≥45 mL/min/1.73m2 (updated Schwartz formula) Exclusion Criteria: * Epstein-Barr virus (EBV) serostatus negative or unknown at time of transplant and screening * History of any treated or biopsy proven acute rejection (BPAR) within 3 months prior to enrollment * Subjects who have experienced more than 1 episode of acute rejection (AR) of the current allograft or any antibody-mediated AR * Subjects with any active infection \[including, but not limited to, positive cytomegalovirus (CMV) or BK viral (BKV) loads, BKV associated nephropathy (BKVAN), CMV retinitis, CMV colitis, etc.\] * Urine albumin:creatinine ratio \> 56.5 mg/mmol (\> 0.5 mg albumin / mg creatinine) on a random voided urine specimen

Locations (8)

University Of Alabama At Birmingham

Birmingham, Alabama, United States

Childrens Hospital Of La

Los Angeles, California, United States

University Of California Los Angeles

Los Angeles, California, United States

Stanford University Medical Center

Outcomes

Primary Outcomes

Maximum Observed Serum Concentration (Cmax) of Belatacept

Cmax was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Cmax was measured in micrograms per milliliter.

Time frame: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57

Time of Maximum Observed Plasma Concentration (Tmax) of Belatacept

Tmax was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Tmax was measured in hours (h).

Time frame: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57

Half-Life of Elimination (T-Half) of Belatacept

T-HALF was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). T-HALF was measured in hours (h).

Time frame: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57

Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC (0-T)) and Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of Belatacept

AUC (0 - T) and AUC (0 - INF) were derived from serum concentration versus time data and measured in microgram hours per milliliter (µg\*h/mL). Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL).

Data from ClinicalTrials.gov

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Secondary Outcomes

Number of Participants With Death, Serious Adverse Events (SAEs), and Treatment-related Adverse Event (AE)

Death was a fatal event leading to permanent cessations of all vital functions of the body. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Adverse event (AE) defined: any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Treatment related=having certain, probable, possible, or missing relationship to study drug.

Time frame: Date of First Dose to 24 weeks post the last dose; approximately 26 weeks

Number of Participants With Positive Belatacept-induced Immunogenicity Response

Serum samples were analyzed for anti-belatacept antibodies using a validated homogenous bridging assay. The assay followed a tiered approach consistent with health authority guidance: tier 1 for screening ADA responses, tier 2 for confirming drug specificity of the ADA-positive responses, and tier 3 for titer. A neutralizing antibody assay was used to test those samples positive to the LEA29Y portion of the molecule in tier 2 and for which drug concentrations are =\>1 μg/mL. Lack of immunogenicity was defined as the absence of a positive response.

Time frame: Baseline/Day 1, Days 15, 29, and 57

Percentage of CD86 Receptor Occupancy

Blood samples collected following the single dose belatacept infusion were assessed for CD86 receptor occupancy (CD86 RO).

Time frame: 0.5 hours post dose on Day 1, Day 29 and Day 57