Objective:
To assess the pharmacokinetics (PK), safety, and efficacy of the first high- purity, plasma-derived factor X concentrate (pdFX) for on-demand treatment of bleeding episodes in a prospective, open-label, multicenter, nonrandomized phase 3 study in subjects with hereditary moderate or severe factor X (FX) deficiency (basal plasma FX activity <5 IU/dL).
Methods:
Included subjects were aged ≥12 years who required treatment with replacement therapy for ≥1 spontaneous or menorrhagic bleed in the past 12 months. Subjects received 25 IU/kg of pdFX on-demand for specific bleeds or as preventative use for 6 months to 2 years. PK was assessed following a single dose at baseline and after ≥6 months. Each bleed was categorized as major or minor, and subjects assessed efficacy for each bleed as “excellent,” “good,” “poor,” or “unassessable”; hospital- treated bleeds were also assessed by investigators. At study end, each investigator assessed the overall efficacy of pdFX. Safety assessments were adverse events (AEs), inhibitor development, viral seroconversions, and changes in laboratory parameters.
Summary:
The study enrolled 16 subjects (aged 12-58 years [mean 27.1 years], 62.5% female) with moderate (n=2) and severe (n=14) FX deficiency. PK parameters did not differ between baseline and repeat assessment visits, with overall mean (median, interquartile range [IQR]) incremental recovery of 2.00 (2.12, 1.79-2.37) IU/dL per IU/kg and half-life of 29.4 (28.6, 25.8-33.1) hours. In total, 468 pdFX infusions were administered; 187 bleeds treated with pdFX were analyzed for efficacy (98 major and 88 minor), of which 155 (82.9%) were treated with one pdFX infusion. A mean (standard deviation) of 1.2 (0.5) infusions per bleed were administered, with a median (IQR) dose of 25.0 (24.4-26.7) IU/kg. Efficacy of pdFX was rated as excellent in 90.9% of bleeds, good in 7.5%, and poor in 1.1%. For the 15 subjects who completed the study, investigators rated overall pdFX efficacy as excellent in 12 (80%) and good in 3 subjects (20%). Six mild/moderate AEs were observed, no serious AEs were considered by investigators to be possibly related to study drug, and no hypersensitivity reactions or clinically significant trends in any laboratory safety parameters were observed.
Conclusions:
In this study, pdFX was safe and efficacious in on-demand treatment of bleeds and short-term preventative therapy in subjects with moderate or severe FX deficiency at a nominal dose of 25 IU/kg. PK results supported these observed hemostatic effects.