Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency

Haemophilia. 2016 May;22(3):419-25. doi: 10.1111/hae.12893. Epub 2016 Mar 8.

Abstract

Introduction: Hereditary factor X (FX) deficiency is a rare bleeding disorder affecting 1:500 000 to 1:1 000 000 of individuals. Until recently, no specific replacement factor concentrate was available.

Aim: The aim of this study was to assess safety and efficacy of a new, high-purity plasma-derived FX concentrate (pdFX) in subjects with hereditary FX deficiency.

Methods: Subjects aged ≥12 years with moderate or severe FX deficiency (plasma FX activity <5 IU dL(-1) ) received 25 IU kg(-1) pdFX as on-demand treatment or short-term prophylaxis for 6 months to 2 years. Subjects assessed pdFX efficacy for each bleed; at end-of-study, investigators assessed overall pdFX efficacy. Blood samples for pharmacokinetic analysis were obtained at baseline and ≥6 months. Safety was assessed by adverse events (AEs), inhibitor development and changes in laboratory parameters.

Results: Sixteen enrolled subjects (six aged 12-17 years; 10 aged 18-58 years) received a total of 468 pdFX infusions. In the 187 analysed bleeds, pdFX efficacy was categorized as excellent, good, poor or unassessable in 90.9%, 7.5%, 1.1% and 0.5% of bleeds respectively; 83% of bleeds were treated with one infusion. For pdFX, mean (median; interquartile range) incremental recovery and half-life were 2.00 (2.12; 1.79-2.37) IU dL(-1) per IU kg(-1) and 29.4 (28.6; 25.8-33.1) h respectively. No serious AEs possibly related to pdFX or evidence of FX inhibitors were observed, and no hypersensitivity reactions or clinically significant trends were detected in laboratory parameters.

Conclusion: These results demonstrate that a dose of 25 IU kg(-1) pdFX is safe and efficacious for on-demand treatment and short-term prophylaxis in subjects with moderate or severe hereditary FX deficiency.

Keywords: clinical trial; clotting factor concentrate; efficacy; factor X deficiency; orphan drug; safety.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Neutralizing / blood
  • Blood Coagulation Tests
  • Child
  • Factor X / adverse effects
  • Factor X / pharmacokinetics
  • Factor X / therapeutic use*
  • Factor X Deficiency / congenital
  • Factor X Deficiency / drug therapy*
  • Factor X Deficiency / pathology
  • Female
  • Half-Life
  • Hemorrhage / prevention & control
  • Humans
  • Male
  • Menorrhagia / prevention & control
  • Middle Aged
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Factor X