1. Recombinant factor VIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A.
- Author
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Young G, Mahlangu J, Kulkarni R, Nolan B, Liesner R, Pasi J, Barnes C, Neelakantan S, Gambino G, Cristiano LM, Pierce GF, and Allen G
- Subjects
- Age Factors, Antibodies, Neutralizing blood, Australia, Child, Child, Preschool, China, Coagulants adverse effects, Coagulants immunology, Coagulants pharmacokinetics, Drug Administration Schedule, Europe, Factor VIII adverse effects, Factor VIII immunology, Factor VIII pharmacokinetics, Female, Half-Life, Hemarthrosis blood, Hemarthrosis diagnosis, Hemophilia A blood, Hemophilia A diagnosis, Humans, Immunoglobulin Fc Fragments adverse effects, Immunoglobulin Fc Fragments immunology, Infusions, Intravenous, Male, North America, Recombinant Fusion Proteins adverse effects, Recombinant Fusion Proteins immunology, Recombinant Fusion Proteins pharmacokinetics, Risk Factors, Severity of Illness Index, South Africa, Treatment Outcome, Coagulants administration & dosage, Factor VIII administration & dosage, Hemarthrosis drug therapy, Hemarthrosis prevention & control, Hemophilia A drug therapy, Hemophilia A prevention & control, Immunoglobulin Fc Fragments administration & dosage, Recombinant Fusion Proteins administration & dosage
- Abstract
Background: Prophylactic factor replacement, which prevents hemarthroses and thereby reduces the musculoskeletal disease burden in children with hemophilia A, requires frequent intravenous infusions (three to four times weekly)., Objective: Kids A-LONG was a phase 3 open-label study evaluating the safety, efficacy and pharmacokinetics of a longer-acting factor, recombinant factor VIII Fc fusion protein (rFVIIIFc), in previously treated children with severe hemophilia A (endogenous FVIII level of < 1 IU dL(-1) [< 1%])., Methods: The study enrolled 71 subjects. The starting rFVIIIFc regimen was twice-weekly prophylaxis (Day 1, 25 IU kg(-1) ; Day 4, 50 IU kg(-1) ); dose (≤ 80 IU kg(-1) ) and dosing interval (≥ 2 days) were adjusted as needed. A subset of subjects had sequential pharmacokinetic evaluations of FVIII and rFVIIIFc. The primary endpoint was development of inhibitors (neutralizing antibodies). Secondary endpoints included pharmacokinetics, annualized bleeding rate (ABR), and number of infusions required to control a bleed., Results: No subject developed an inhibitor to rFVIIIFc. Adverse events were typical of a pediatric hemophilic population. The rFVIIIFc half-life was prolonged relative to that of FVIII, consistent with observations in adults and adolescents. The median ABR was 1.96 overall, and 0.00 for spontaneous bleeds; 46.4% of subjects reported no bleeding episodes on study. Ninety-three per cent of bleeding episodes were controlled with one to two infusions. The median average weekly rFVIIIFc prophylactic dose was 88.11 IU kg(-1) . At study end, 62 of 69 subjects (90%) were infusing twice weekly. Among subjects who had been previously receiving FVIII prophylaxis, 74% reduced their dosing frequency with rFVIIIFc., Conclusion: Twice-weekly infusions with rFVIIIFc were well tolerated and yielded low bleeding rates in children with severe hemophilia A., (© 2015 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.)
- Published
- 2015
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