title: Nonacog beta pegol (N9-GP) in haemophilia B: A multinational phase III safety and efficacy extension trial (paradigm™4).
abstract: BACKGROUND
  Paradigm™4 was an international extension trial investigating the safety and efficacy of nonacog beta pegol, a recombinant glycoPEGylated factor IX (FIX) with extended half-life, in haemophilia B patients (FIX activity ≤2%; aged 13-70years) who had previously participated in phase III pivotal (paradigm™2) or surgery (paradigm™3) trials.
  
  
  METHODS
  Patients chose to continue treatment with nonacog beta pegol in either one of two once-weekly prophylaxis arms (10IU/kg or 40IU/kg), or an on-demand arm (40IU/kg for mild/moderate bleeds; 80IU/kg for severe bleeds). The primary objective was to evaluate immunogenicity; key secondary objectives included assessing safety and haemostatic efficacy in the treatment and prevention of bleeds.
  
  
  RESULTS
  Seventy-one patients received prophylaxis or on-demand treatment. No patient developed an inhibitor and no safety concerns were identified. The success rate for the treatment of reported bleeds was 94.6%; most (87.9%) resolved with one injection. The median annualised bleeding rate for patients on prophylaxis was 1.36 (interquartile range [IQR] 0.00-2.23) and 1.00 (IQR 0.00-2.03) for the 10 and 40IU/kg treatment arms, respectively. The mean FIX activity trough achieved for 10 and 40IU once weekly was 9.8% and 21.3%, respectively. Fourteen patients on prophylaxis underwent 23 minor surgical procedures; haemostatic perioperative outcomes for all of those evaluated were 'excellent' or 'good'.
  
  
  CONCLUSIONS
  Nonacog beta pegol showed a favourable tolerability profile (with no safety issues identified) with good prophylactic protection and control of bleeding in previously treated adult and adolescent haemophilia B patients.
authors.affiliation: Hemostasis and Thrombosis Center, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, United States. Electronic address: gyoung@chla.usc.edu.
authors.forename: Guy
authors.initials: G
authors.lastname: Young
authors.affiliation: Arthur Bloom Haemophilia Centre, Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Collins
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Colberg
authors.affiliation: Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Ampaiwan
authors.initials: A
authors.lastname: Chuansumrit
authors.affiliation: Department of Hematology, Ogikubo Hospital, Tokyo, Japan.
authors.forename: Hideji
authors.initials: H
authors.lastname: Hanabusa
authors.affiliation: Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, United States.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Lentz
authors.affiliation: Haemophilia Comprehensive Care Centre, Faculty of Health Sciences, NHLS and University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Johnny
authors.initials: J
authors.lastname: Mahlangu
authors.affiliation: Van Creveldkliniek, University Medical Centre, Utrecht, The Netherlands.
authors.forename: Evelien P
authors.initials: EP
authors.lastname: Mauser-Bunschoten
authors.affiliation: Hôpital Edouard Herriot, University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Négrier
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
authors.affiliation: Erciyes University Medical Faculty, Kayseri, Turkey.
authors.forename: Turkan
authors.initials: T
authors.lastname: Patiroglu
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ca' Granda Foundation, Maggiore Hospital Policlinico, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Santagostino
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Ramin
authors.initials: R
authors.lastname: Tehranchi
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Marek
authors.initials: M
authors.lastname: Zak
authors.affiliation: Haemophilia Center, National Blood Centre, Kuala Lumpur, Malaysia.
authors.forename: Faraizah Abdul
authors.initials: FA
authors.lastname: Karim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005164:Factor IX / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002836:Hemophilia B / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control; D006470:Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control; D006490:Hemostatics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D006490:Hemostatics; D011994:Recombinant Proteins; C000592276:nonacog beta pegol; D011092:Polyethylene Glycols; D005164:Factor IX
keywords: Factor IX; Haemophilia B; Half-life; Nonacog beta pegol; Prophylaxis