Purpose: To assess the pharmacokinetics (PK) and pharmacodynamic (PD) effect of a single dose of belatacept (bela) administered to adolescent kidney transplant recipients (KTR).

Methods: In a phase I trial, 9 EBV-positive KTR aged 13–17 yrs (mean 15.1 yrs) on calcineurin inhibitor-based immunosuppression for >6 months post-transplant received one IV bela infusion (7.5 mg/kg, 30 min). Blood was collected for PK serially over Days 1–57. PD was measured by % CD86 receptor occupancy (%CD86RO). Blood was collected for %CD86RO on Days 1, 29, and 57. Adverse events (AEs) were recorded to Day 57 and serious AEs (SAEs) to Month 6.

Results: All 9 completed the study. Mean half-life (t_1/2), volume of distribution (V_ss), and systemic clearance (CL) in adolescent KTR were comparable to historical values from healthy adult volunteers (HV) and adult KTR (Table). Mean %CD86RO increased with increasing bela concentration, suggesting a pharmacologic PK/PD relationship (Figure). Four SAEs were reported; none was deemed related to bela.

Conclusions: In adolescent KTR, the range of PK values was similar to those seen in HV and adult KTR. The PK/PD relationship between %CD86RO and bela concentration was similar to that seen in adults, providing a basis for dose selection in future adolescent studies. A single dose of bela was well tolerated in the 9 adolescent KTR. Presented at ASN Kidney Week 2017 in New Orleans, LA.

CITATION INFORMATION: Moudgil A., Dharnidharka V., Feig D., Warshaw B., Perera V., Murthy B., Roberts M., Polinsky M., Ettenger R. Single-Dose Pharmacokinetics and Pharmacodynamics of Belatacept in Adolescent Kidney Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

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