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.

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.

• Authors: R Liesner, C Akanezi, M Norton, J Payne
• Journal: Haemophilia : the official journal of the World Federation of Hemophilia (Haemophilia) Vol. 24 Issue 6 Pg. 941-949 (Nov 2018) ISSN: 1365-2516 [Electronic] England
• PMID: 29707881 (Publication Type: Clinical Trial, Phase III, Journal Article)
• Copyright: © 2018 The Authors Haemophilia Published by John Wiley & Sons Ltd.

Chemical References

• Factor X

Topics

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