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Completed

NCT Number: NCT01791491

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

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.

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Key information

Conditions

Kidney Transplant

Age range

12 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University Of Alabama At Birmingham, Birmingham, Alabama, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Belatacept

Drug

Single intravenous infusion of belatacept, 7.5 mg/kg

Other names: BMS-224818

Primary outcomes

  1. Maximum Observed Serum Concentration (Cmax) of Belatacept

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

    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.

  2. Time of Maximum Observed Plasma Concentration (Tmax) of Belatacept

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

    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).

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

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

    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).

  4. 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

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

    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).

  5. Total Body Clearance (CLT) of Belatacept

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

    CLT was the volume of abatacept cleared by the system, normalized by baseline body weight. 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). CLT was measured in milliliters per hours per kilogram of body weight (mL/h/kg).

  6. Volume of Distribution at Steady-state (Vss) of Belatacept

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

    Vss 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). Vss was measured in liters per kg body weight (L/kg).

Secondary outcomes

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

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

    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.

  2. Number of Participants With Positive Belatacept-induced Immunogenicity Response

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

    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.

  3. Percentage of CD86 Receptor Occupancy

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

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

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Registry information

Official study title

A Phase 2 Multi-Center, Randomized Conversion Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Belatacept Administered to Pediatric Subjects With a Stable Renal Transplant

Important dates

Study start
2013
Primary completion
2016
Study completion
2016
First posted
Feb 15, 2013
Registry last updated
Jul 24, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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