Objectives:
This prospective clinical trial was conducted to assess the safety, hemostatic efficacy and pharmacokinetic (PK) profile of a recently developed recombinant factor IX (BAX326*) in pediatric previously-treated patients (PTPs) with severe or moderately severe hemophilia B.
Methods:
PTPs aged <12 years with severe (FIX level < 1%) or moderately severe (FIX level ≤ 2%) hemophilia B were eligible for enrollment. BAX326 was administered as prophylaxis twice a week over 6-months, and on demand for treatment of bleeds. Efficacy was evaluated by treatment response rating (excellent, good, fair, none) and annualized bleeding rate (ABR). PK assessments after one 75 ± 5 IU/kg infusion of BAX326 were assessed using a non-linear mixed model (population PK) approach. IR was measured as part of the PK evaluation 30 minutes after the initial PK infusion and at 5, 13 and 26 weeks after the initial infusion.
Summary:
Nine subjects (39.1%) had no bleeds during the study. A total of 26 bleeds occurred (mean ABR 2.7 ±3.14, median 2.0), of which 2 were spontaneous. Fewer bleeds occurred in joints than in non-joint sites (19 non joint vs. 7 joint bleeds). Hemostatic efficacy was excellent or good in >96% of bleeds, and the majority (88.5%) resolved after 1-2 infusions. The median IR (IU/dl)/(IU/kg) at the initial PK assessment was 0.685 (range: 0.31- 1.00). As expected, a higher IR was observed in association with increased patient age; IR was slightly lower in subjects < 6 years (median 0.591; range: 0.31-0.75), than in subjects aged 6 to <12 years (median 0.714; range: 0.51-1.00). IR was consistent over time. There were no adverse reactions, no thrombotic events and no hypersensitivity reactions. None of the subjects treated (N=23) developed inhibitory or specific binding antibodies against FIX.
Conclusions:
BAX326 is efficacious and safe as prophylactic treatment as well as for bleed control in pediatric hemophilia B patients.
*Licensed in the USA and Australia (Rixubis®; Baxter Healthcare Corp., USA).