Journal article
Nonacog beta pegol (N9-GP) in haemophilia B: A multinational phase III safety and efficacy extension trial (paradigm™4)
Thrombosis research, Vol.141, pp.69-76
05/2016
DOI: 10.1016/j.thromres.2016.02.030
PMID: 26970716
Abstract
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.
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.
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’.
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.
•Nonacog beta pegol is an extended half-life glycoPEGylated factor IX (FIX).•It was designed to enable prophylaxis with high activity levels/fewer weekly doses.•Paradigm™4 was an open-label, international extension trial of nonacog beta pegol.•Safety/efficacy data were collected on prophylaxis and the treatment of bleeds.•Nonacog beta pegol was well tolerated and efficacious in haemophilia B patients.
Details
- Title: Subtitle
- Nonacog beta pegol (N9-GP) in haemophilia B: A multinational phase III safety and efficacy extension trial (paradigm™4)
- Creators
- Guy Young - Hemostasis and Thrombosis Center, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, United StatesPeter W Collins - Arthur Bloom Haemophilia Centre, Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United KingdomTorben Colberg - Novo Nordisk A/S, Søborg, DenmarkAmpaiwan Chuansumrit - Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandHideji Hanabusa - Department of Hematology, Ogikubo Hospital, Tokyo, JapanSteven R Lentz - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, United StatesJohnny Mahlangu - Haemophilia Comprehensive Care Centre, Faculty of Health Sciences, NHLS and University of the Witwatersrand, Johannesburg, South AfricaEvelien P Mauser-Bunschoten - Van Creveldkliniek, University Medical Centre, Utrecht, The NetherlandsClaude Négrier - Hôpital Edouard Herriot, University Claude Bernard Lyon 1, Lyon, FranceJohannes Oldenburg - Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, GermanyTurkan Patiroglu - Erciyes University Medical Faculty, Kayseri, TurkeyElena Santagostino - Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ca' Granda Foundation, Maggiore Hospital Policlinico, Milan, ItalyRamin Tehranchi - Novo Nordisk A/S, Søborg, DenmarkMarek Zak - Novo Nordisk A/S, Søborg, DenmarkFaraizah Abdul Karim - Haemophilia Center, National Blood Centre, Kuala Lumpur, Malaysia
- Resource Type
- Journal article
- Publication Details
- Thrombosis research, Vol.141, pp.69-76
- DOI
- 10.1016/j.thromres.2016.02.030
- PMID
- 26970716
- NLM abbreviation
- Thromb Res
- ISSN
- 0049-3848
- eISSN
- 1879-2472
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/501100004191, name: Novo Nordisk
- Language
- English
- Date published
- 05/2016
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094532102771
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