Efficacy, Safety and Pharmacokinetic Results of a Phase III, Open-Label, Multicenter Study with a Plasma-Derived Von Willebrand Factor (VWF)/Factor VIII (FVIII) Concentrate in Pediatric Patients <12 Years of Age with Hemophilia A (SWIFTLY-HA Study)

Background: Plasma-derived von Willebrand factor/factor VIII (pdVWF/FVIII; VONCENTO (R), CSL Behring) is a high-concentration, low-volume, high-purity concentrate, with a high level of VWF high-molecular-weight multimers and a VWF/FVIII ratio of similar to 2.4:1. Methods: This study (NCT01229007) investigated the pharmacokinetics (PK), efficacy and safety of pdVWF/FVIII in 35 previously treated (minimum 20 exposure days [EDs]) pediatric patients (<12 years) with severe hemophilia A. PK was evaluated with a single 50 IU FVIII/kg dose of pdVWF/FVIII. Efficacy and safety analyses were performed during on-demand treatment (n=17) or prophylaxis (n=18) for up to 100 EDs with a maximum study duration of 12 months. Results: PK profiles were similar for patients aged <6 years and those aged 6-12 years, and, as expected, the youngest patients had an increased clearance. On-demand patients reported 320 non-surgical bleeding (NSB) events and received a median number of 29.0 infusions (median dose 34.2 IU FVIII/kg). Hemostatic efficacy was assessed by the investigator as excellent/good in all cases (24%/76%). The 18 patients in the prophylaxis arm experienced 173 NSB events (97 NSBs [56%] in three patients). Five patients (28%) had no NSB events. Overall, patients received a median number of 92 infusions (median dose 30.6 IU FVIII/kg). The majority of bleeds (92%) were successfully controlled with only one infusion. Hemostatic efficacy was assessed by the investigator as excellent (86%) or good (14%). Inhibitors occurred in three patients of which two were transient (low titer) and one persisted (high titer). These three patients had known risk factors for inhibitor development. Conclusion: This study demonstrated comparable PK profiles for pediatric patients aged <6 years and aged 6-12 years, and an excellent efficacy and safety profile in this population. The adverse events reported were mostly mild to moderate with inhibitor rates within the expected incidence range.