title: Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: St. George's Haemophilia Centre, St. George's University Hospitals NHS Foundation Trust, London, UK.
authors.forename: S K
authors.initials: SK
authors.lastname: Austin
authors.affiliation: Department of Pediatric Hematology, Children's Hospital, Ege University Faculty of Medicine, Izmir, Turkey.
authors.forename: K
authors.initials: K
authors.lastname: Kavakli
authors.affiliation: Bio Products Laboratory, Elstree, UK.
authors.forename: M
authors.initials: M
authors.lastname: Norton
authors.affiliation: Angelo Bianchi Bonomi Hemophilia & Thrombosis Center, Milan, Italy.|Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Peyvandi
authors.affiliation: Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Shapiro
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D001780:Blood Coagulation Tests; D002648:Child; D005170:Factor X / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005171:Factor X Deficiency / Q000151:congenital / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006207:Half-Life; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D008297:Male; D008595:Menorrhagia / Q000517:prevention & control; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D005170:Factor X
keywords: clinical trial; clotting factor concentrate; efficacy; factor X deficiency; orphan drug; safety