{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:35:34Z","timestamp":1787654134795,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,9,14]],"date-time":"2015-09-14T00:00:00Z","timestamp":1442188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Octapharma AG"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Nuwiq<jats:sup>\u00ae<\/jats:sup> (Human\u2010cl rh<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content>) is a new\u2010generation recombinant factor <jats:styled-content style=\"fixed-case\">VIII<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">rFVIII<\/jats:styled-content>) protein, without chemical modification or fusion to any other protein, produced in a human cell line.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim\/Methods<\/jats:title><jats:p>This prospective, open\u2010label, multinational phase <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> study assessed the efficacy and safety of Human\u2010cl rh<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> in 59 previously treated patients (<jats:styled-content style=\"fixed-case\">PTP<\/jats:styled-content>s) with severe haemophilia A aged 2\u201312 years (2\u20135 [<jats:italic>N<\/jats:italic> = 29]; 6\u201312 [<jats:italic>N<\/jats:italic> = 30]) during standard prophylaxis (\u226550 exposure days and \u22656 months). Efficacy in treating breakthrough bleeds and during surgical prophylaxis was also assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>An initial pharmacokinetic assessment (<jats:italic>N<\/jats:italic> = 13 per age subgroup) demonstrated comparable results with the one\u2010stage and chromogenic assays. Mean (<jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content>) half\u2010life was 11.9 (5.4) and 13.1 (2.6) hours in children aged 2\u20135 years and 6\u201312 years respectively (one\u2010stage assay). Prophylactic efficacy, based on mean monthly bleeding rate, was \u2018excellent\u2019 or \u2018good\u2019 in 91.5% of children for all bleeds and in 96.6% of children for spontaneous bleeds. Mean (<jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content>) annualized bleeding rate was 4.12 (5.22) [median 1.9] for all bleeds, 1.50 (3.32) [median 0] for spontaneous bleeds and 2.34 (3.54) [median 1.57] for traumatic bleeds. There were no major, life\u2010threatening bleeds. Efficacy was \u2018excellent\u2019 or \u2018good\u2019 in the treatment of 82.4% of breakthrough bleeds. Overall efficacy during five major surgeries was rated as \u2018excellent\u2019. There were no <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> inhibitors or treatment\u2010related serious adverse events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results in paediatric <jats:styled-content style=\"fixed-case\">PTP<\/jats:styled-content>s indicate that Human\u2010cl rh<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> is effective for the prevention and treatment of bleeds.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.12797","type":"journal-article","created":{"date-parts":[[2015,9,15]],"date-time":"2015-09-15T02:58:49Z","timestamp":1442285929000},"page":"232-239","source":"Crossref","is-referenced-by-count":40,"title":["Novel, human cell line\u2010derived recombinant factor <scp>VIII<\/scp> (Human\u2010cl rh<scp>FVIII<\/scp>, Nuwiq<sup>\u00ae<\/sup>) in children with severe haemophilia A: efficacy, safety and pharmacokinetics"],"prefix":"10.1111","volume":"22","author":[{"given":"A.","family":"Klukowska","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Hematology and Oncology Warsaw Medical University Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5336-261X","authenticated-orcid":false,"given":"T.","family":"Szczepa\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology and Oncology Zabrze Medical University of Silesia Katowice Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Vdovin","sequence":"additional","affiliation":[{"name":"Moscow Children's Hematology Centre Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Knaub","sequence":"additional","affiliation":[{"name":"Octapharma AG Lachen Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Octapharma Pharmazeutika Produktionsges.mbH Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Liesner","sequence":"additional","affiliation":[{"name":"Great Ormond Street Hospital for Children NHS Trust Haemophilia Centre London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/JBM.S6885"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2005.01065.x"},{"key":"e_1_2_8_4_1","unstructured":"BrowerC ThompsonA. Hemophilia A. Available athttp:\/\/www.ncbi.nlm.nih.gov\/bookshelf\/br.fcgi?book=gene&part=hemo-a. Accessed March 27 2015."},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1615621"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1297164"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01722.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01947.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2012.02827.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.2003.00780.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02032.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1538-7836.2004.00710.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01518.x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-03-0941"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1208024"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12335"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01864.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-009-9119-y"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)35234-1"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2012.09.011"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1385\/MB:28:3:241"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2012.01804.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2012.08.311"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(90)81427-P"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42401-5"},{"key":"e_1_2_8_26_1","unstructured":"European Medicines Agency.Guideline on the investigation of human plasma\u2010derived factor VIII and IX products. London;2011. Report No.: EMA\/CHMP\/BPWP\/144533\/2009."},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1653759"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2002-32658"},{"key":"e_1_2_8_29_1","unstructured":"Baxter.Advate\u00aePrescribing Information July2012."},{"key":"e_1_2_8_30_1","unstructured":"Bayer HealthCare.Kogenate\u00aeFS Prescribing Information 2012."},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.03757.x"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2008.03032.x"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12165"},{"key":"e_1_2_8_34_1","unstructured":"Biogen Idec Inc.Eloctate [antihemophilic factor (recombinant) Fc fusion protein]. Prescribing Information June2014."},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2004.00932.x"},{"issue":"1","key":"e_1_2_8_36_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/hae.12322","article-title":"The first recombinant FVIII produced in human cells \u2013an update on its clinical development programme","volume":"20","author":"Valentino LA","year":"2014","journal-title":"Haemophilia"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01312.x"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhae.12797","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.12797","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hae.12797","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.12797","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T13:14:41Z","timestamp":1695561281000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.12797"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,14]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1111\/hae.12797"],"URL":"https:\/\/doi.org\/10.1111\/hae.12797","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,14]]}}}