Pharmacokinetics of recombinant factor XIII at steady state in patients with congenital factor XIII A-subunit deficiency

B. Kerlin*, B. Brand, A. Inbal, S. Halimeh, D. Nugent, M. Lundblad, R. Tehranchi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The use of monthly recombinant factor XIII (rFXIII) recently demonstrated favorable safety and efficacy for congenital FXIII A-subunit deficiency patients aged ≥ 6 years (mentor1 trial), although the pharmacokinetics (PK) were not fully evaluated. Objectives: To comprehensively evaluate the steady-state PK of rFXIII in patients aged ≥ 6 years with congenital FXIII A-subunit deficiency. Patients/methods: mentor2 is an ongoing, multinational safety and efficacy trial in which patients are receiving monthly rFXIII (35 IU kg-1) for ≥ 52 weeks. For this 28-day PK analysis, blood samples were collected immediately predosing, and 1 h, 2 h, 3, 7, 14, 21, and 28 days postdosing. FXIII activity was measured and PK parameters were calculated using non-compartmental analysis, without prior baseline adjustment. Information regarding adverse events and bleeding was collected at each visit. Antibody assessments were performed predosing and at day 28. Results: PK analysis in 23 patients revealed first-order elimination of rFXIII with a geometric mean half-life of 13.6 days. Mean FXIII activity was > 0.1 IU mL-1 throughout the 28-day period, with a geometric mean peak activity of 0.87 IU mL-1 and trough of 0.16 IU mL-1. The geometric mean clearance was 0.15 mL h-1 kg-1. No bleeding episodes occurred during the PK session, and no anti-rFXIII antibodies were detected. Peak and trough FXIII activities were constant over time, compared with previous activities (≥ 10 rFXIII doses) in the same patients. Conclusions: Clearance of rFXIII is unaffected over time, and monthly prophylaxis with 35 IU kg-1 rFXIII provides FXIII activity > 0.1 IU mL-1 throughout the dosing interval in patients with congenital FXIII A-subunit deficiency.

Original languageEnglish
Pages (from-to)2038-2043
Number of pages6
JournalJournal of Thrombosis and Haemostasis
Volume12
Issue number12
DOIs
StatePublished - 1 Dec 2014

Keywords

  • Factor XIII
  • Factor XIII deficiency
  • Fibrinolysis
  • Pharmacokinetics
  • Recombinant factor XIII-A2

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