Search

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 (pd FX) 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 pd FX efficacy for each bleed; at end-of-study, investigators assessed overall pd FX 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 pd FX infusions. In the 187 analysed bleeds, pd FX 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 pd FX, 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 pd FX 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. [ABSTRACT FROM AUTHOR]

Introduction Hereditary factor X ( FX) deficiency affects 1:500 000 to 1:1 000 000 of individuals. There are few published data on the pharmacokinetics ( PK) of FX for existing treatments for FX deficiency, and no specific replacement factor concentrate exists. A high-purity plasma-derived FX concentrate (pd FX) has been developed for use as replacement therapy in subjects with hereditary FX deficiency. Aim This analysis assessed pd FX PK after a single 25 IU kg−1 bolus dose in subjects with hereditary moderate or severe FX deficiency (plasma FX activity [ FX:C] <5 IU dL−1). Methods For a baseline PK assessment, blood samples were taken predose and at intervals up to 144 h (7 days) post dose. After ≥6 months of on-demand pd FX treatment and treatment of ≥1 bleed with pd FX, subjects underwent repeat PK assessment. Samples were assayed for plasma FX:C (measured using the clotting and chromogenic assays) and FX antigen. Results FX:C peaked at 0.4-0.5 h and subsequently declined over the course of 144 h with a biphasic decay curve. PK parameters observed at the baseline ( n = 16) and repeat ( n = 15) assessments were equivalent, therefore summary PK values were obtained by combining data from both visits ( n = 31). The mean terminal half-life and incremental recovery of pd FX was 29.4 h and 2.00 IU dL−1 per IU kg−1 respectively. Conclusion This is the most comprehensive PK study to date in subjects with hereditary FX deficiency. These results are consistent with the observed haemostatic efficacy of pd FX and provide the PK data required for the treatment of hereditary FX deficiency using pd FX replacement therapy. [ABSTRACT FROM AUTHOR]