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 (pd FX ) concentrate

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 (pd FX ) is available in the United States and European Union as replacement therapy for FXD , but data are scarce on pd FX use in children <12 years. Aim This prospective, open‐label phase 3 study assessed the safety, efficacy and pharmacokinetics of pd FX in children <12 years with moderate/severe FXD . Methods Subjects aged <12 years with basal plasma FX activity ( FX :C) <5 IU / dL received pd FX 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 pd FX efficacy for preventing/decreasing bleeds. Secondary endpoints included number and severity of bleeds, trough FX :C and incremental recovery. Safety parameters were adverse events ( AE s), 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 pd FX 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 AE s 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 pd FX for treating children <12 years with moderate/severe hereditary FXD .