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)

Abstract

Claudia Djambas Khayat,1 Genadi Iosava,2 Irina Romashevskaya,3 Oleksandra Stasyshyn,4 Marta Julia Lopez,5 Maria Teresa Pompa,6 Tobias Rogosch,7 Wilfried Seifert7 1Hospital Hôtel Dieu de France, Saint Joseph University, Beirut, Lebanon; 2Joint Stock Hematology and Transfusiology Research Institute, Tbilisi, Georgia; 3Republican Research Centre of Radiation Medicine and Human Ecology, Gomel, Belarus; 4Institute of Blood Pathology and Transfusion Medicine, Lviv, Ukraine; 5Guatemala City Hospital Roosevelt, Guatemala, Guatemala; 6Monterrey Nuevo Leon OCA Hospital (MIRC), Monterrey Nuevo Leon, Mexico; 7CSL Behring, Clinical Research and Development, Marburg, GermanyCorrespondence: Claudia Djambas KhayatHospital Hôtel Dieu de France, Saint Joseph University, Beirut, LebanonTel [phone]Email [email protected]: Plasma-derived von Willebrand factor/factor VIII (pdVWF/FVIII; VONCENTO®, 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 ∼ 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.Keywords: hemophilia A, von Willebrand factor, factor VIII, on-demand therapy, prophylaxis, hemostatic efficacy

Keywords

• hemophilia a
• von willebrand factor
• factor viii
• on-demand therapy
• prophylaxis
• hemostatic efficacy