Phase I study of single-dose pharmacokinetics and pharmacodynamics of belatacept in adolescent kidney transplant recipients

Asha Moudgil, Vikas R. Dharnidharka, Daniel I. Feig, Barry L. Warshaw, Vidya Perera, Bindu Murthy, Mustimbo E. Roberts, Martin S. Polinsky, Robert B. Ettenger

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Belatacept is an intravenously infused selective T cell costimulation blocker approved for preventing organ rejection in renal transplant recipients aged ≥18 years. This phase I trial examined the pharmacokinetics and pharmacodynamics (percentage CD86 receptor occupancy [%CD86RO]) of a single dose of belatacept (7.5 mg/kg) administered to kidney transplant recipients aged 12-17 years receiving a stable calcineurin inhibitor–based immunosuppressive regimen. Nine adolescents (mean age 15.1 years) who were seropositive for Epstein-Barr virus were enrolled; all completed the 6-month study. Pharmacokinetics suggested relatively low variability of exposure (coefficients of variation for maximum observed serum concentration [C max ] and area under the serum concentration-time curve from time zero extrapolated to infinity [AUC 0- INF ] were 20% and 25%, respectively). Mean half-life (T 1/2 ) occurred 7.2 days postinfusion. Belatacept total body clearance was 0.48 mL/h/kg, and volume of distribution at steady-state (V ss ) was low at 0.09 L/kg. Compared with historical data from healthy adult volunteers administered a single dose of belatacept 10 mg/kg and adult kidney transplant recipients administered multiple doses of belatacept 5 mg/kg, pharmacokinetic values for adolescents were similar, indicating consistency across adolescent and adult populations. Mean %CD86RO increased with increasing belatacept concentration, indicating a direct relationship between pharmacokinetics and pharmacodynamics. Four patients reported 7 serious adverse events; none was considered related to belatacept. These data will inform belatacept dose selection in future studies of adolescent kidney transplant recipients.

Original languageEnglish
Pages (from-to)1218-1223
Number of pages6
JournalAmerican Journal of Transplantation
Volume19
Issue number4
DOIs
StatePublished - Apr 2019

Keywords

  • belatacept
  • clinical research/practice
  • immunosuppressant - fusion proteins and monoclonal antibodies
  • kidney transplantation
  • kidney transplantation/nephrology
  • living donor
  • pharmacokinetics/pharmacodynamics
  • simulation

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