Pathfinder 5 enrolled 68 children (34 aged 0-5 y, 34 aged 6-11 y), 95% previously on prophylaxis 62 completed the extension, amounting to 306 patient-years (32,138 exposure days) with mean exposure of 4.5 years. For 15 severe bleeds, the median total dose was 111 IU/kg per episode.

In subjects receiving prophylaxis, the median initial dose matched the prophylaxis dose (52 IU/kg), and 76% of bleeds received a single dose. For participants who were in the on-demand arm, the median initial dose was 28 IU/kg, with 88.4% of bleeds treated with a single dose.

Treatment of bleeding through extension 1 is described in Table the median dose for mild/moderate bleeds was 42 IU/kg. Through the study (mean 3.5 years), 177 adolescents/adults on doses of ~52 IU/kg Q4D had a median ABR of 0.99 and mean (95% CI) FVIII trough levels of 3.1 (2.6-3.4) IU/dL. In the main phase, 105 of 175 adolescents/adults on prophylaxis (50 IU/kg Q4D) experienced 436 bleeds with a median annualized bleeding rate (ABR) of 1.2. On-demand patients (n=12) treated for a total of 37 patient-years of exposure reported 1,270 (46%) bleeds. Results: Pathfinder 2 enrolled 186 patients (46 from the US) with 128 (69%) completing the second extension phase encompassing 785 patient-years (66,577 exposure days) with 2,758 treated bleeds. For surgery, a pre-trial test dose of 50 IU/kg was administered with PK assessment and then dosing in the study was to achieve desired FVIII suggested by World Federation of Hemophilia guidelines. Children (aged <12 y) on prophylaxis were administered a target of 60 (50-75) IU/kg N8-GP twice weekly. For the on-demand treatment arm, patients were to be given 20 to 70 IU/kg, depending on bleed severity and desired FVIII levels. Methods: Adolescents/adults (aged в‰Ґ12 y) were administered 50 IU/kg N8-GP every 4 days (Q4D) as routine prophylaxis in the main phase alternative weekly dosing was explored in 2 extension phases. The pathfinder trials evaluated routine prophylaxis and bleed treatment in previously treated adolescents/adults (pathfinder 2) and children (pathfinder 5) with severe hemophilia A and perioperative management of major surgery (pathfinder 3). N8-GP (ESPEROCT В®) is an extended half-life recombinant FVIII product.

Individual variability in pharmacokinetics (PK) has resulted in dosing ranges, rather than fixed doses. Introduction: Replacement factor VIII (FVIII) products have been administered to achieve desired FVIII levels for bleed treatment, perioperative management, or routine prophylaxis.

Pathfinder office trial