Safety and efficacy of a glycoPEGylated rFVIII (turoctocog alpha pegol, N8-GP) in paediatric patients with severe haemophilia A
Summary Turoctocog alfa pegol (N8-GP, Novo Nordisk, Bagsværd, Denmark), an extended half-life glycoPEGylated recombinant factor VIII (rFVIII), is being developed for prophylaxis and treatment of bleeds in haemophilia A patients. pathfinder ™ 5 is a multinational, open-label, single-arm trial to asse...
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| Veröffentlicht in: | Thrombosis and haemostasis 2017, Vol.117 (9), p.1705-1713 |
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| creator | Meunier, Sandrine Alamelu, Jayanthi Ehrenforth, Silke Hanabusa, Hideji Karim, Faraizah Abdul Kavakli, Kaan Khodaie, Melanie Staber, Janice Stasyshyn, Oleksandra Yee, Donald L. Rageliene, Lina |
| description | Summary
Turoctocog alfa pegol (N8-GP, Novo Nordisk, Bagsværd, Denmark), an extended half-life glycoPEGylated recombinant factor VIII (rFVIII), is being developed for prophylaxis and treatment of bleeds in haemophilia A patients. pathfinder
™
5 is a multinational, open-label, single-arm trial to assess safety, efficacy and pharmacokinetics of N8-GP in paediatric (150 ED for patients aged 6–11 years [older cohort]) were included. For prophylaxis, N8-GP was dosed at 50–75 IU/kg twice weekly; bleeds were treated with 20–75 IU/kg. Half-life was estimated for the patients’ previous FVIII product and for N8-GP. Sixty-eight patients received N8-GP; none developed inhibitors and no other concerns were identified. Median annualised bleeding rate was 1.95 (1.94 and 1.97 in the younger and older cohorts, respectively). Twenty-nine patients (42.6 %; 15 younger and 14 older children, respectively) did not report any bleeding while on N8-GP prophylaxis; 39 patients (57.4 %; 19 younger and 20 older children, respectively) reported 70 bleeds (all mild/moderate). N8-GP treatment was successful for 78.6 % of bleeds in all patients, 80.0 % in younger and 77.5 % in older patients. Most bleeds (80.0 %) were treated with ≤2 injections. Half-life ratio between N8-GP and the patients’ previous FVIII product was 1.85. N8-GP was well tolerated and provided effective prophylaxis and treatment of bleeds in paediatric patients with severe haemophilia A.
Trial registered at
http://www.clinicaltrials.gov
(NCT01731600).
Supplementary Material to this article is available online at www.thrombosis-online.com. |
| doi_str_mv | 10.1160/TH17-03-0166 |
| format | Article |
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Turoctocog alfa pegol (N8-GP, Novo Nordisk, Bagsværd, Denmark), an extended half-life glycoPEGylated recombinant factor VIII (rFVIII), is being developed for prophylaxis and treatment of bleeds in haemophilia A patients. pathfinder
™
5 is a multinational, open-label, single-arm trial to assess safety, efficacy and pharmacokinetics of N8-GP in paediatric (<12 years), previously treated patients. Boys with severe haemophilia A (<1 % FVIII), no history of inhibitors and previously treated with FVIII products (>50 exposure days [ED] for patients aged 0–5 years [younger cohort]; >150 ED for patients aged 6–11 years [older cohort]) were included. For prophylaxis, N8-GP was dosed at 50–75 IU/kg twice weekly; bleeds were treated with 20–75 IU/kg. Half-life was estimated for the patients’ previous FVIII product and for N8-GP. Sixty-eight patients received N8-GP; none developed inhibitors and no other concerns were identified. Median annualised bleeding rate was 1.95 (1.94 and 1.97 in the younger and older cohorts, respectively). Twenty-nine patients (42.6 %; 15 younger and 14 older children, respectively) did not report any bleeding while on N8-GP prophylaxis; 39 patients (57.4 %; 19 younger and 20 older children, respectively) reported 70 bleeds (all mild/moderate). N8-GP treatment was successful for 78.6 % of bleeds in all patients, 80.0 % in younger and 77.5 % in older patients. Most bleeds (80.0 %) were treated with ≤2 injections. Half-life ratio between N8-GP and the patients’ previous FVIII product was 1.85. N8-GP was well tolerated and provided effective prophylaxis and treatment of bleeds in paediatric patients with severe haemophilia A.
Trial registered at
http://www.clinicaltrials.gov
(NCT01731600).
Supplementary Material to this article is available online at www.thrombosis-online.com.</description><identifier>ISSN: 0340-6245</identifier><identifier>EISSN: 2567-689X</identifier><identifier>DOI: 10.1160/TH17-03-0166</identifier><identifier>PMID: 28692108</identifier><language>eng</language><publisher>Germany: Schattauer GmbH</publisher><subject>Asia ; Child ; Child, Preschool ; Coagulants - adverse effects ; Coagulants - pharmacokinetics ; Coagulants - therapeutic use ; Coagulation and Fibrinolysis ; Europe ; Factor VIII - adverse effects ; Factor VIII - pharmacokinetics ; Factor VIII - therapeutic use ; Half-Life ; Hemarthrosis - blood ; Hemarthrosis - diagnosis ; Hemarthrosis - prevention & control ; Hemophilia A - blood ; Hemophilia A - diagnosis ; Hemophilia A - drug therapy ; Humans ; Infant ; Infant, Newborn ; Male ; North America ; Patient Safety ; Risk Assessment ; Severity of Illness Index ; Treatment Outcome</subject><ispartof>Thrombosis and haemostasis, 2017, Vol.117 (9), p.1705-1713</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c327t-70eaf5f4c1f8f6b02463fcecb04123399441eb0cec5395a52f2c71c36810193b3</citedby><cites>FETCH-LOGICAL-c327t-70eaf5f4c1f8f6b02463fcecb04123399441eb0cec5395a52f2c71c36810193b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.thieme-connect.de/products/ejournals/pdf/10.1160/TH17-03-0166.pdf$$EPDF$$P50$$Gthieme$$H</linktopdf><linktohtml>$$Uhttps://www.thieme-connect.de/products/ejournals/html/10.1160/TH17-03-0166$$EHTML$$P50$$Gthieme$$H</linktohtml><link.rule.ids>314,776,780,3005,4010,27900,27901,27902,54534,54535</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28692108$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Meunier, Sandrine</creatorcontrib><creatorcontrib>Alamelu, Jayanthi</creatorcontrib><creatorcontrib>Ehrenforth, Silke</creatorcontrib><creatorcontrib>Hanabusa, Hideji</creatorcontrib><creatorcontrib>Karim, Faraizah Abdul</creatorcontrib><creatorcontrib>Kavakli, Kaan</creatorcontrib><creatorcontrib>Khodaie, Melanie</creatorcontrib><creatorcontrib>Staber, Janice</creatorcontrib><creatorcontrib>Stasyshyn, Oleksandra</creatorcontrib><creatorcontrib>Yee, Donald L.</creatorcontrib><creatorcontrib>Rageliene, Lina</creatorcontrib><title>Safety and efficacy of a glycoPEGylated rFVIII (turoctocog alpha pegol, N8-GP) in paediatric patients with severe haemophilia A</title><title>Thrombosis and haemostasis</title><addtitle>Thromb Haemost</addtitle><description>Summary
Turoctocog alfa pegol (N8-GP, Novo Nordisk, Bagsværd, Denmark), an extended half-life glycoPEGylated recombinant factor VIII (rFVIII), is being developed for prophylaxis and treatment of bleeds in haemophilia A patients. pathfinder
™
5 is a multinational, open-label, single-arm trial to assess safety, efficacy and pharmacokinetics of N8-GP in paediatric (<12 years), previously treated patients. Boys with severe haemophilia A (<1 % FVIII), no history of inhibitors and previously treated with FVIII products (>50 exposure days [ED] for patients aged 0–5 years [younger cohort]; >150 ED for patients aged 6–11 years [older cohort]) were included. For prophylaxis, N8-GP was dosed at 50–75 IU/kg twice weekly; bleeds were treated with 20–75 IU/kg. Half-life was estimated for the patients’ previous FVIII product and for N8-GP. Sixty-eight patients received N8-GP; none developed inhibitors and no other concerns were identified. Median annualised bleeding rate was 1.95 (1.94 and 1.97 in the younger and older cohorts, respectively). Twenty-nine patients (42.6 %; 15 younger and 14 older children, respectively) did not report any bleeding while on N8-GP prophylaxis; 39 patients (57.4 %; 19 younger and 20 older children, respectively) reported 70 bleeds (all mild/moderate). N8-GP treatment was successful for 78.6 % of bleeds in all patients, 80.0 % in younger and 77.5 % in older patients. Most bleeds (80.0 %) were treated with ≤2 injections. Half-life ratio between N8-GP and the patients’ previous FVIII product was 1.85. N8-GP was well tolerated and provided effective prophylaxis and treatment of bleeds in paediatric patients with severe haemophilia A.
Trial registered at
http://www.clinicaltrials.gov
(NCT01731600).
Supplementary Material to this article is available online at www.thrombosis-online.com.</description><subject>Asia</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Coagulants - adverse effects</subject><subject>Coagulants - pharmacokinetics</subject><subject>Coagulants - therapeutic use</subject><subject>Coagulation and Fibrinolysis</subject><subject>Europe</subject><subject>Factor VIII - adverse effects</subject><subject>Factor VIII - pharmacokinetics</subject><subject>Factor VIII - therapeutic use</subject><subject>Half-Life</subject><subject>Hemarthrosis - blood</subject><subject>Hemarthrosis - diagnosis</subject><subject>Hemarthrosis - prevention & control</subject><subject>Hemophilia A - blood</subject><subject>Hemophilia A - diagnosis</subject><subject>Hemophilia A - drug therapy</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Male</subject><subject>North America</subject><subject>Patient Safety</subject><subject>Risk Assessment</subject><subject>Severity of Illness Index</subject><subject>Treatment Outcome</subject><issn>0340-6245</issn><issn>2567-689X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkEtLw0AUhQdRbK3uXMssFRudRzJJlqX0BUULVnEXJtM7zZS0EyZTJSv_uilVV67u4fJx4HwIXVPyQKkgj8spjQPCA0KFOEFdFok4EEn6foq6hIckECyMOuiirjekRcI0OkcdloiUUZJ00deL1OAbLHcrDFobJVWDrcYSr8tG2cVo0pTSwwq78dtsNsO3fu-s8lbZNZZlVUhcwdqWffyUBJPFHTY7XElYGemdUW30Bna-xp_GF7iGD3CACwlbWxWmNBIPLtGZlmUNVz-3h17Ho-VwGsyfJ7PhYB4ozmIfxASkjnSoqE60yAkLBdcKVE5CyjhP0zCkkJP2E_E0khHTTMVUcZFQQlOe8x7qH3uVs3XtQGeVM1vpmoyS7OAxO3jMCM8OHlv85ohX-3wLqz_4V1wL3B8BXxjYQraxe7drB_xf9w1LQ3rz</recordid><startdate>2017</startdate><enddate>2017</enddate><creator>Meunier, Sandrine</creator><creator>Alamelu, Jayanthi</creator><creator>Ehrenforth, Silke</creator><creator>Hanabusa, Hideji</creator><creator>Karim, Faraizah Abdul</creator><creator>Kavakli, Kaan</creator><creator>Khodaie, Melanie</creator><creator>Staber, Janice</creator><creator>Stasyshyn, Oleksandra</creator><creator>Yee, Donald L.</creator><creator>Rageliene, Lina</creator><general>Schattauer GmbH</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>2017</creationdate><title>Safety and efficacy of a glycoPEGylated rFVIII (turoctocog alpha pegol, N8-GP) in paediatric patients with severe haemophilia A</title><author>Meunier, Sandrine ; Alamelu, Jayanthi ; Ehrenforth, Silke ; Hanabusa, Hideji ; Karim, Faraizah Abdul ; Kavakli, Kaan ; Khodaie, Melanie ; Staber, Janice ; Stasyshyn, Oleksandra ; Yee, Donald L. ; Rageliene, Lina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c327t-70eaf5f4c1f8f6b02463fcecb04123399441eb0cec5395a52f2c71c36810193b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Asia</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Coagulants - adverse effects</topic><topic>Coagulants - pharmacokinetics</topic><topic>Coagulants - therapeutic use</topic><topic>Coagulation and Fibrinolysis</topic><topic>Europe</topic><topic>Factor VIII - adverse effects</topic><topic>Factor VIII - pharmacokinetics</topic><topic>Factor VIII - therapeutic use</topic><topic>Half-Life</topic><topic>Hemarthrosis - blood</topic><topic>Hemarthrosis - diagnosis</topic><topic>Hemarthrosis - prevention & control</topic><topic>Hemophilia A - blood</topic><topic>Hemophilia A - diagnosis</topic><topic>Hemophilia A - drug therapy</topic><topic>Humans</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>Male</topic><topic>North America</topic><topic>Patient Safety</topic><topic>Risk Assessment</topic><topic>Severity of Illness Index</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Meunier, Sandrine</creatorcontrib><creatorcontrib>Alamelu, Jayanthi</creatorcontrib><creatorcontrib>Ehrenforth, Silke</creatorcontrib><creatorcontrib>Hanabusa, Hideji</creatorcontrib><creatorcontrib>Karim, Faraizah Abdul</creatorcontrib><creatorcontrib>Kavakli, Kaan</creatorcontrib><creatorcontrib>Khodaie, Melanie</creatorcontrib><creatorcontrib>Staber, Janice</creatorcontrib><creatorcontrib>Stasyshyn, Oleksandra</creatorcontrib><creatorcontrib>Yee, Donald L.</creatorcontrib><creatorcontrib>Rageliene, Lina</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Meunier, Sandrine</au><au>Alamelu, Jayanthi</au><au>Ehrenforth, Silke</au><au>Hanabusa, Hideji</au><au>Karim, Faraizah Abdul</au><au>Kavakli, Kaan</au><au>Khodaie, Melanie</au><au>Staber, Janice</au><au>Stasyshyn, Oleksandra</au><au>Yee, Donald L.</au><au>Rageliene, Lina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Safety and efficacy of a glycoPEGylated rFVIII (turoctocog alpha pegol, N8-GP) in paediatric patients with severe haemophilia A</atitle><jtitle>Thrombosis and haemostasis</jtitle><addtitle>Thromb Haemost</addtitle><date>2017</date><risdate>2017</risdate><volume>117</volume><issue>9</issue><spage>1705</spage><epage>1713</epage><pages>1705-1713</pages><issn>0340-6245</issn><eissn>2567-689X</eissn><abstract>Summary
Turoctocog alfa pegol (N8-GP, Novo Nordisk, Bagsværd, Denmark), an extended half-life glycoPEGylated recombinant factor VIII (rFVIII), is being developed for prophylaxis and treatment of bleeds in haemophilia A patients. pathfinder
™
5 is a multinational, open-label, single-arm trial to assess safety, efficacy and pharmacokinetics of N8-GP in paediatric (<12 years), previously treated patients. Boys with severe haemophilia A (<1 % FVIII), no history of inhibitors and previously treated with FVIII products (>50 exposure days [ED] for patients aged 0–5 years [younger cohort]; >150 ED for patients aged 6–11 years [older cohort]) were included. For prophylaxis, N8-GP was dosed at 50–75 IU/kg twice weekly; bleeds were treated with 20–75 IU/kg. Half-life was estimated for the patients’ previous FVIII product and for N8-GP. Sixty-eight patients received N8-GP; none developed inhibitors and no other concerns were identified. Median annualised bleeding rate was 1.95 (1.94 and 1.97 in the younger and older cohorts, respectively). Twenty-nine patients (42.6 %; 15 younger and 14 older children, respectively) did not report any bleeding while on N8-GP prophylaxis; 39 patients (57.4 %; 19 younger and 20 older children, respectively) reported 70 bleeds (all mild/moderate). N8-GP treatment was successful for 78.6 % of bleeds in all patients, 80.0 % in younger and 77.5 % in older patients. Most bleeds (80.0 %) were treated with ≤2 injections. Half-life ratio between N8-GP and the patients’ previous FVIII product was 1.85. N8-GP was well tolerated and provided effective prophylaxis and treatment of bleeds in paediatric patients with severe haemophilia A.
Trial registered at
http://www.clinicaltrials.gov
(NCT01731600).
Supplementary Material to this article is available online at www.thrombosis-online.com.</abstract><cop>Germany</cop><pub>Schattauer GmbH</pub><pmid>28692108</pmid><doi>10.1160/TH17-03-0166</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0340-6245 |
| ispartof | Thrombosis and haemostasis, 2017, Vol.117 (9), p.1705-1713 |
| issn | 0340-6245 2567-689X |
| language | eng |
| recordid | cdi_crossref_primary_10_1160_TH17_03_0166 |
| source | MEDLINE; Thieme Connect Journals |
| subjects | Asia Child Child, Preschool Coagulants - adverse effects Coagulants - pharmacokinetics Coagulants - therapeutic use Coagulation and Fibrinolysis Europe Factor VIII - adverse effects Factor VIII - pharmacokinetics Factor VIII - therapeutic use Half-Life Hemarthrosis - blood Hemarthrosis - diagnosis Hemarthrosis - prevention & control Hemophilia A - blood Hemophilia A - diagnosis Hemophilia A - drug therapy Humans Infant Infant, Newborn Male North America Patient Safety Risk Assessment Severity of Illness Index Treatment Outcome |
| title | Safety and efficacy of a glycoPEGylated rFVIII (turoctocog alpha pegol, N8-GP) in paediatric patients with severe haemophilia A |
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