title: Nonacog beta pegol in previously treated children with hemophilia B: results from an international open-label phase 3 trial.
abstract: Essentials Nonacog beta pegol is a recombinant glycoPEGylated factor IX with an extended half-life. This phase 3 trial investigated its safety/efficacy in previously treated hemophilia B boys ≤ 12 years. A 40 IU kg(-1) dose provided effective once-weekly prophylaxis and hemostasis when used to treat bleeds. Nonacog beta pegol was well tolerated in previously treated boys ≤ 12 years with hemophilia B.
  
  
  
  Background Nonacog beta pegol is a recombinant glycoPEGylated factor IX with an extended half-life, developed to improve care for patients with hemophilia B. Objectives To investigate the safety, efficacy and pharmacokinetics of nonacog beta pegol for the prophylaxis and treatment of bleeds in previously treated children with hemophilia B. Patients/Methods This phase 3 trial, paradigm(™) 5, enrolled and treated 25 children (aged ≤ 12 years) with hemophilia B (FIX ≤ 2%). Patients were stratified by age (0-6 years and 7-12 years), and received once-weekly prophylaxis with 40 IU kg(-1) nonacog beta pegol for 50 exposure days. Results No patient developed inhibitors, and no safety concerns were identified. Forty-two bleeds in 15 patients were reported to have been treated; the overall success rate was 92.9%, and most bleeds (85.7%) resolved after one dose. The median annualized bleeding rates (ABRs; bleeds per patient per year) were 1.0 in the total population, 0.0 in the 0-6-year group, and 2.0 in the 7-12-year group; the estimated mean ABRs were 1.44 in the total population, 0.87 in the 0-6-year group, and 1.88 in the 7-12-year group. For 22 patients who had previously been receiving prophylaxis, the estimated mean ABR was 1.38 versus a historical ABR of 2.51. Estimated mean steady-state FIX trough levels were 0.153 IU mL(-1) (0-6 years) and 0.190 IU mL(-1) (7-12 years). Conclusion Nonacog beta pegol was well tolerated in previously treated children with hemophilia B; a 40 IU kg(-1) dose provided effective once-weekly prophylaxis and hemostasis when bleeds were treated.
authors.affiliation: Division of Haematology/Oncology, Department of Paediatrics and Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Carcao
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Zak
authors.affiliation: Hemophilia Center, National Blood Center, Kuala Lumpur, Malaysia.
authors.forename: F
authors.initials: F
authors.lastname: Abdul Karim
authors.affiliation: Ogikubo Hospital, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hanabusa
authors.affiliation: Hemophilia Treatment Center, Children's Hospital and Clinics of Minnesota, Minneapolis, MN, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kearney
authors.affiliation: NTUH, Children's and Women's Hospital, Taipei, Taiwan.
authors.forename: M-Y
authors.initials: MY
authors.lastname: Lu
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Persson
authors.affiliation: Haemophilia, Haemostasis & Thrombosis Centre, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK.
authors.forename: S
authors.initials: S
authors.lastname: Rangarajan
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ca' Granda Foundation, Maggiore Hospital Policlinico, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Santagostino
mesh_terms: D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005164:Factor IX / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002836:Hemophilia B / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D006470:Hemorrhage; D006487:Hemostasis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011092:Polyethylene Glycols / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; C000592276:nonacog beta pegol; D011092:Polyethylene Glycols; D005164:Factor IX
keywords: factor IX; hemophilia B; nonacog beta pegol; pediatrics; prophylaxis