{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:40:02Z","timestamp":1791463202618,"version":"4.3.4"},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"05","license":[{"start":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T00:00:00Z","timestamp":1588636800000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Novo Nordisk A\/S"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Long-term safety and efficacy data of extended half-life factor IX (FIX) prophylaxis in children with hemophilia B (HB) are sparse. paradigm 5 is a multinational, open-label, single-arm, phase III trial assessing once-weekly (40\u2009IU\/kg) prophylactic nonacog beta pegol (N9-GP) in previously treated patients (PTPs) aged \u2264 12 years with HB (FIX activity \u2264 2%). Primary endpoint: incidence of anti-FIX inhibitory antibodies (\u2265 0.6 Bethesda Units). We present a 5-year analysis (N\u2009=\u200925, including remaining patients with \u2265 5 years' follow-up) and compare with a 1-year analysis (\u2265 52 weeks' exposure). The main phase enrolled 25 children; 22 entered the extension phase; 17 remained in trial at data cutoff. Median treatment period: 5.6 years\/patient; median total number of N9-GP exposure days: 290.0\/patient. No patients developed anti-FIX inhibitory antibodies. No other safety concerns, including thromboembolic events, were reported. Neurological examinations have not revealed any new abnormal findings. Sixteen (64.0%) patients remained free from spontaneous bleeds; all bleeds were mild\/moderate in severity; 93.0% were controlled with 1 to 2\u2009N9-GP injections. No intracranial hemorrhages were reported. Annualized bleeding rates (ABRs) were very low at 5 years (median\/Poisson-estimated mean overall ABR: 0.66\/0.99), having decreased from the 1-year analysis (1.00\/1.44). Median\/Poisson-estimated mean spontaneous ABRs for the 1- and 5-year analyses: 0.00\/0.45 and 0.00\/0.33. Mean FIX trough activity at 5 years: 17.9%. Mean polyethylene glycol plasma concentration reached steady state at 6 months, increasing slightly over time, in line with increased FIX trough activity. N9-GP administered for \u2265 5 years shows favorable long-term safety and efficacy in PTPs with HB (FIX activity \u2264 2%).<\/jats:p>","DOI":"10.1055\/s-0040-1709521","type":"journal-article","created":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T18:37:44Z","timestamp":1588703864000},"page":"737-746","source":"Crossref","is-referenced-by-count":17,"title":["Long-Term Safety and Efficacy of Nonacog Beta Pegol (N9-GP) Administered for at Least 5 Years in Previously Treated Children with Hemophilia B"],"prefix":"10.1055","volume":"120","author":[{"given":"Manuel","family":"Carcao","sequence":"additional","affiliation":[{"name":"Division of Haematology\/Oncology, Department of Paediatrics and Child Health Evaluative Sciences, Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Kearney","sequence":"additional","affiliation":[{"name":"Center for Bleeding and Clotting Disorders, Children's Hospital of Minnesota, Minneapolis, Minnesota, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng Yao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Taki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yokohama City Seibu Hospital, St. Marianna University School of Medicine, Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Rubens","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunduo","family":"Shen","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Santagostino","sequence":"additional","affiliation":[{"name":"Foundation IRCCS C\u00e1 Granda, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Maggiore Hospital Policlinico, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2020,5,5]]},"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0040-1709521.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T18:37:48Z","timestamp":1588703868000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0040-1709521"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5]]},"references-count":0,"journal-issue":{"issue":"05","published-online":{"date-parts":[[2020,5,5]]},"published-print":{"date-parts":[[2020,5]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0040-1709521","relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5]]}}}