Prophylactic treatment of bleeding episodes in children <12 years with moderate to severe hereditary factor X deficiency (FXD): Efficacy and safety of a high-purity plasma-derived factor X (pdFX) concentrate

Haemophilia. 2018 Nov;24(6):941-949. doi: 10.1111/hae.13500. Epub 2018 Apr 30.

Abstract

Background: Hereditary factor X (FX) deficiency (FXD) affects 1:500 000-1:1 000 000 people worldwide. A novel, high-purity plasma-derived FX concentrate (pdFX) is available in the United States and European Union as replacement therapy for FXD, but data are scarce on pdFX use in children <12 years.

Aim: This prospective, open-label phase 3 study assessed the safety, efficacy and pharmacokinetics of pdFX in children <12 years with moderate/severe FXD.

Methods: Subjects aged <12 years with basal plasma FX activity (FX:C) <5 IU/dL received pdFX as prophylactic and on-demand treatment, with doses adjusted to maintain FX:C > 5 IU/dL. After ≥26 weeks and ≥50 exposure days, investigators rated pdFX efficacy for preventing/decreasing bleeds. Secondary endpoints included number and severity of bleeds, trough FX:C and incremental recovery. Safety parameters were adverse events (AEs), inhibitor development and changes in laboratory parameters.

Results: The study enrolled 9 subjects (0-5 years, n = 4; 6-11 years, n = 5) with severe (n = 8) or moderate (n = 1) FXD. At end of study, investigators rated pdFX efficacy excellent for all subjects. Ten bleeds occurred (n = 3 subjects; 6 major, 3 minor, 1 unassessed for severity). Trough FX:C levels remained >5 IU/dL for all subjects after the last dose adjustment study visit. Mean incremental recovery was significantly lower for younger vs older subjects (1.53 vs 1.91 IU/dL per IU/kg; P = .001). All AEs were unrelated to treatment; no inhibitor development or clinically significant changes in laboratory parameters were observed.

Conclusions: These results demonstrate the efficacy and safety of pdFX for treating children <12 years with moderate/severe hereditary FXD.

Keywords: clotting factor concentrate; efficacy; factor X deficiency; paediatric; safety.

Publication types

  • Clinical Trial, Phase III

MeSH terms

  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Factor X / adverse effects
  • Factor X / metabolism
  • Factor X / pharmacokinetics
  • Factor X / pharmacology*
  • Factor X Deficiency / complications*
  • Female
  • Hemorrhage / complications*
  • Hemorrhage / prevention & control*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Plasma / metabolism*
  • Safety*

Substances

  • Factor X

Grants and funding