Abstract: SA-PO504

Single-Dose (SD) Pharmacokinetics (PK), Pharmacodynamics (PD), and Safety of Belatacept (Bela) in Adolescent Kidney Transplant Recipients (KTRs)

Session Information

Category: Transplantation

  • 1702 Transplantation: Clinical and Translational

Authors

  • Moudgil, Asha, Children's National Medical Center, Washington, District of Columbia, United States
  • Dharnidharka, Vikas R., Washington University, St Louis, Missouri, United States
  • Feig, Daniel, University of Alabama, Birmingham, Alabama, United States
  • Warshaw, Barry L., Emory University & Children's Healthcare of Atlanta, Atlanta, Georgia, United States
  • Perera, Vidya, Bristol-Myers Squibb, Princeton, New Jersey, United States
  • Murthy, Bindu, Bristol-Myers Squibb, Princeton, New Jersey, United States
  • Polinsky, Martin, Bristol-Myers Squibb, Princeton, New Jersey, United States
  • Ettenger, Robert B., University of California, Los Angeles, California, United States
Background

Bela blocks CD86-CD28 co-stimulation between antigen presenting cells and T-cells. It is approved for rejection prophylaxis in KTR >18 yrs old. A phase I trial of adolescent KTR assessed SD bela PK and its PD effect, measured by % CD86 receptor occupancy (%CD86RO).

Methods

9 EBV-positive KTR aged 13–17 yrs (mean 15.1 yrs) on CNI-based immunosuppression for >6 months post-KT received one IV bela infusion (7.5 mg/kg, 30 min). Blood was collected for PK serially over Days 1–57 and 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 (t1/2), volume of distribution (Vss), and systemic clearance (CL) in adolescent KTR were comparable to values from healthy adult volunteers (HV) and adult KTR (Table), indicating consistency across adolescent and adult populations. Mean %CD86RO increased with increasing bela concentration, indicating a direct PK/PD relationship (Figure). Three had 7 AEs, with 4 SAEs; all SAEs were considered unrelated to bela.

Conclusion

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. SD bela was well tolerated in the 9 adolescent KTR.

 Adolescent KTR
(SD 7.5 mg/kg)
HV
(SD 10 mg/kg)
Adult KTR
(multiple doses 5 mg/kg)
Cmax, µg/mL151 (20)300 (25.7)139 (20.1)
t½, h173 (46.8)235 (28.5)196.8 (29.2)
CL, mL/h/kg0.48 (27)0.39 (17.9)0.51 (27.4)
Vss, L/kg0.09 (30)0.09 (22.2)0.12 (25.0)
AUC, µg●h/mL15407 (25)*26398 (19.6)*14090 (27.3)

Data are mean (coefficient of variation as a %) *AUC0–inf AUC0–tau, where tau=4 wks

Funding

  • Commercial Support