Long-Acting Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) in Children
Identifieur interne : 000805 ( Pmc/Checkpoint ); précédent : 000804; suivant : 000806Long-Acting Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) in Children
Auteurs : Gili Kenet [Israël] ; Hervé Chambost [France] ; Christoph Male [Autriche] ; Thierry Lambert [France] ; Susan Halimeh [Allemagne] ; Tatiana Chernova [Russie] ; Maria Elisa Mancuso [Italie] ; Julie Curtin [Australie] ; Christine Voigt [États-Unis] ; Yanyan Li [États-Unis] ; Iris Jacobs [États-Unis] ; Elena Santagostino [Italie]Source :
- Thrombosis and Haemostasis [ 0340-6245 ] ; 2016.
Abstract
A global phase 3 study evaluated the pharmacokinetics, efficacy and safety of a recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 27 previously treated male children (1–11 years) with severe and moderately severe haemophilia B (factor IX [FIX] activity ≤2 IU/dl). All patients received routine prophylaxis once every seven days for up to 77 weeks, and treated any bleeding episodes on-demand. The mean terminal half-life of rIX-FP was 91.4 hours (h), 4.3-fold longer than previous FIX treatment and clearance was 1.11 ml/h/kg, 6.4-fold slower than previous FIX treatment. The median (Q1, Q3) annualised spontaneous bleeding rate was 0.00 (0.00, 0.91) and was similar between the <6 years and ≥6 years age groups, with a weekly median prophylactic dose of 46 IU/kg. In addition, patients maintained a median trough level of 13.4 IU/dl FIX activity on weekly prophylaxis. Overall, 97.2% of bleeding episodes were successfully treated with one or two injections of rIX-FP (95% CI: 92% to 99%), 88.7% with one injection, and 96% of the treatments were rated effective (excellent or good) by the Investigator. No patient developed FIX inhibitors and no safety concerns were identified. These results indicate that rIX-FP is safe and effective for preventing and treating bleeding episodes in children with haemophilia B with weekly prophylaxis. Routine prophylaxis with rIX-FP at treatment intervals of up to 14 days are currently being investigated in children with severe and moderately severe haemophilia B. Clinicaltrials.gov (NCT01662531)
Url:
DOI: 10.1160/TH16-03-0179
PubMed: 27583313
PubMed Central: 5039316
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
PMC:5039316Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Long-Acting Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) in Children</title>
<author><name sortKey="Kenet, Gili" sort="Kenet, Gili" uniqKey="Kenet G" first="Gili" last="Kenet">Gili Kenet</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><institution>The Israeli National Hemophilia Center, Sheba Medical Center, tel Hashomer, Sackler Medical School</institution>
,<addr-line>tel Aviv University, Israel</addr-line>
</nlm:aff>
<country xml:lang="fr">Israël</country>
<wicri:regionArea>tel Aviv University</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chambost, Herve" sort="Chambost, Herve" uniqKey="Chambost H" first="Hervé" last="Chambost">Hervé Chambost</name>
<affiliation wicri:level="1"><nlm:aff id="aff002">Pediatric Hematology Oncology Department,<institution>Children Hospital La Timone, APHM, Aix Marseille University</institution>
,<addr-line>Marseille, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Marseille</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Male, Christoph" sort="Male, Christoph" uniqKey="Male C" first="Christoph" last="Male">Christoph Male</name>
<affiliation wicri:level="1"><nlm:aff id="aff003">Department of Pediatrics,<institution>Medical University of Vienna</institution>
,<addr-line>Vienna, Austria</addr-line>
</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Vienna</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lambert, Thierry" sort="Lambert, Thierry" uniqKey="Lambert T" first="Thierry" last="Lambert">Thierry Lambert</name>
<affiliation wicri:level="3"><nlm:aff id="aff004"><institution>Centre de Traitement des ’Hémophilies</institution>
,<addr-line>Hôpital Bicetre, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Hôpital Bicetre, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Halimeh, Susan" sort="Halimeh, Susan" uniqKey="Halimeh S" first="Susan" last="Halimeh">Susan Halimeh</name>
<affiliation wicri:level="1"><nlm:aff id="aff005"><institution>CRC Coagulation Research Centre GmbH</institution>
,<addr-line>Duisburg, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Duisburg</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chernova, Tatiana" sort="Chernova, Tatiana" uniqKey="Chernova T" first="Tatiana" last="Chernova">Tatiana Chernova</name>
<affiliation wicri:level="1"><nlm:aff id="aff006"><institution>Kirov Research Institute of Hematology and Blood Transfusion</institution>
,<addr-line>Kirov, Russia</addr-line>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Kirov</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mancuso, Maria Elisa" sort="Mancuso, Maria Elisa" uniqKey="Mancuso M" first="Maria Elisa" last="Mancuso">Maria Elisa Mancuso</name>
<affiliation wicri:level="1"><nlm:aff id="aff007"><institution>Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico</institution>
,<addr-line>Milan, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Milan</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Curtin, Julie" sort="Curtin, Julie" uniqKey="Curtin J" first="Julie" last="Curtin">Julie Curtin</name>
<affiliation wicri:level="1"><nlm:aff id="aff008"><institution>Children’s Hospital at Westmead, Sydney Children’s Hospital Network</institution>
,<addr-line>Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Sydney</wicri:regionArea>
</affiliation>
<affiliation><nlm:aff id="aff009"><institution>Discipline of Paediatrics and Child Health, University of Sydney</institution>
,<addr-line>Australia</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Voigt, Christine" sort="Voigt, Christine" uniqKey="Voigt C" first="Christine" last="Voigt">Christine Voigt</name>
<affiliation wicri:level="1"><nlm:aff id="aff010"><institution>CSL Behring, CRD, King of Prussia</institution>
,<addr-line>Pennsylvania, USA</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Pennsylvania</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Li, Yanyan" sort="Li, Yanyan" uniqKey="Li Y" first="Yanyan" last="Li">Yanyan Li</name>
<affiliation wicri:level="1"><nlm:aff id="aff010"><institution>CSL Behring, CRD, King of Prussia</institution>
,<addr-line>Pennsylvania, USA</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Pennsylvania</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jacobs, Iris" sort="Jacobs, Iris" uniqKey="Jacobs I" first="Iris" last="Jacobs">Iris Jacobs</name>
<affiliation wicri:level="1"><nlm:aff id="aff010"><institution>CSL Behring, CRD, King of Prussia</institution>
,<addr-line>Pennsylvania, USA</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Pennsylvania</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Santagostino, Elena" sort="Santagostino, Elena" uniqKey="Santagostino E" first="Elena" last="Santagostino">Elena Santagostino</name>
<affiliation wicri:level="1"><nlm:aff id="aff007"><institution>Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico</institution>
,<addr-line>Milan, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Milan</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">27583313</idno>
<idno type="pmc">5039316</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039316</idno>
<idno type="RBID">PMC:5039316</idno>
<idno type="doi">10.1160/TH16-03-0179</idno>
<date when="2016">2016</date>
<idno type="wicri:Area/Pmc/Corpus">002D32</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002D32</idno>
<idno type="wicri:Area/Pmc/Curation">002B82</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002B82</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000805</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000805</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Long-Acting Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) in Children</title>
<author><name sortKey="Kenet, Gili" sort="Kenet, Gili" uniqKey="Kenet G" first="Gili" last="Kenet">Gili Kenet</name>
<affiliation wicri:level="1"><nlm:aff id="aff001"><institution>The Israeli National Hemophilia Center, Sheba Medical Center, tel Hashomer, Sackler Medical School</institution>
,<addr-line>tel Aviv University, Israel</addr-line>
</nlm:aff>
<country xml:lang="fr">Israël</country>
<wicri:regionArea>tel Aviv University</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chambost, Herve" sort="Chambost, Herve" uniqKey="Chambost H" first="Hervé" last="Chambost">Hervé Chambost</name>
<affiliation wicri:level="1"><nlm:aff id="aff002">Pediatric Hematology Oncology Department,<institution>Children Hospital La Timone, APHM, Aix Marseille University</institution>
,<addr-line>Marseille, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Marseille</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Male, Christoph" sort="Male, Christoph" uniqKey="Male C" first="Christoph" last="Male">Christoph Male</name>
<affiliation wicri:level="1"><nlm:aff id="aff003">Department of Pediatrics,<institution>Medical University of Vienna</institution>
,<addr-line>Vienna, Austria</addr-line>
</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Vienna</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lambert, Thierry" sort="Lambert, Thierry" uniqKey="Lambert T" first="Thierry" last="Lambert">Thierry Lambert</name>
<affiliation wicri:level="3"><nlm:aff id="aff004"><institution>Centre de Traitement des ’Hémophilies</institution>
,<addr-line>Hôpital Bicetre, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Hôpital Bicetre, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Halimeh, Susan" sort="Halimeh, Susan" uniqKey="Halimeh S" first="Susan" last="Halimeh">Susan Halimeh</name>
<affiliation wicri:level="1"><nlm:aff id="aff005"><institution>CRC Coagulation Research Centre GmbH</institution>
,<addr-line>Duisburg, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Duisburg</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chernova, Tatiana" sort="Chernova, Tatiana" uniqKey="Chernova T" first="Tatiana" last="Chernova">Tatiana Chernova</name>
<affiliation wicri:level="1"><nlm:aff id="aff006"><institution>Kirov Research Institute of Hematology and Blood Transfusion</institution>
,<addr-line>Kirov, Russia</addr-line>
</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Kirov</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mancuso, Maria Elisa" sort="Mancuso, Maria Elisa" uniqKey="Mancuso M" first="Maria Elisa" last="Mancuso">Maria Elisa Mancuso</name>
<affiliation wicri:level="1"><nlm:aff id="aff007"><institution>Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico</institution>
,<addr-line>Milan, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Milan</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Curtin, Julie" sort="Curtin, Julie" uniqKey="Curtin J" first="Julie" last="Curtin">Julie Curtin</name>
<affiliation wicri:level="1"><nlm:aff id="aff008"><institution>Children’s Hospital at Westmead, Sydney Children’s Hospital Network</institution>
,<addr-line>Sydney, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Sydney</wicri:regionArea>
</affiliation>
<affiliation><nlm:aff id="aff009"><institution>Discipline of Paediatrics and Child Health, University of Sydney</institution>
,<addr-line>Australia</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Voigt, Christine" sort="Voigt, Christine" uniqKey="Voigt C" first="Christine" last="Voigt">Christine Voigt</name>
<affiliation wicri:level="1"><nlm:aff id="aff010"><institution>CSL Behring, CRD, King of Prussia</institution>
,<addr-line>Pennsylvania, USA</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Pennsylvania</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Li, Yanyan" sort="Li, Yanyan" uniqKey="Li Y" first="Yanyan" last="Li">Yanyan Li</name>
<affiliation wicri:level="1"><nlm:aff id="aff010"><institution>CSL Behring, CRD, King of Prussia</institution>
,<addr-line>Pennsylvania, USA</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Pennsylvania</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jacobs, Iris" sort="Jacobs, Iris" uniqKey="Jacobs I" first="Iris" last="Jacobs">Iris Jacobs</name>
<affiliation wicri:level="1"><nlm:aff id="aff010"><institution>CSL Behring, CRD, King of Prussia</institution>
,<addr-line>Pennsylvania, USA</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Pennsylvania</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Santagostino, Elena" sort="Santagostino, Elena" uniqKey="Santagostino E" first="Elena" last="Santagostino">Elena Santagostino</name>
<affiliation wicri:level="1"><nlm:aff id="aff007"><institution>Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico</institution>
,<addr-line>Milan, Italy</addr-line>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Milan</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Thrombosis and Haemostasis</title>
<idno type="ISSN">0340-6245</idno>
<imprint><date when="2016">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>Summary</title>
<p>A global phase 3 study evaluated the pharmacokinetics, efficacy and safety of a recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 27 previously treated male children (1–11 years) with severe and moderately severe haemophilia B (factor IX [FIX] activity ≤2 IU/dl). All patients received routine prophylaxis once every seven days for up to 77 weeks, and treated any bleeding episodes on-demand. The mean terminal half-life of rIX-FP was 91.4 hours (h), 4.3-fold longer than previous FIX treatment and clearance was 1.11 ml/h/kg, 6.4-fold slower than previous FIX treatment. The median (Q1, Q3) annualised spontaneous bleeding rate was 0.00 (0.00, 0.91) and was similar between the <6 years and ≥6 years age groups, with a weekly median prophylactic dose of 46 IU/kg. In addition, patients maintained a median trough level of 13.4 IU/dl FIX activity on weekly prophylaxis. Overall, 97.2% of bleeding episodes were successfully treated with one or two injections of rIX-FP (95% CI: 92% to 99%), 88.7% with one injection, and 96% of the treatments were rated effective (excellent or good) by the Investigator. No patient developed FIX inhibitors and no safety concerns were identified. These results indicate that rIX-FP is safe and effective for preventing and treating bleeding episodes in children with haemophilia B with weekly prophylaxis. Routine prophylaxis with rIX-FP at treatment intervals of up to 14 days are currently being investigated in children with severe and moderately severe haemophilia B. Clinicaltrials.gov (NCT01662531)</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bolton Maggs, Phb" uniqKey="Bolton Maggs P">PHB Bolton-Maggs</name>
</author>
<author><name sortKey="Pasi, Kj" uniqKey="Pasi K">KJ. Pasi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Srivastava, A" uniqKey="Srivastava A">A Srivastava</name>
</author>
<author><name sortKey="Brewer, Ak" uniqKey="Brewer A">AK Brewer</name>
</author>
<author><name sortKey="Mauser Bunschoten, Ep" uniqKey="Mauser Bunschoten E">EP Mauser-Bunschoten</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Santagostino, E" uniqKey="Santagostino E">E Santagostino</name>
</author>
<author><name sortKey="Mancuso, Me" uniqKey="Mancuso M">ME. Mancuso</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Santagostino, E" uniqKey="Santagostino E">E Santagostino</name>
</author>
<author><name sortKey="Negrier, C" uniqKey="Negrier C">C Negrier</name>
</author>
<author><name sortKey="Klamroth, R" uniqKey="Klamroth R">R Klamroth</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Martinowitz, U" uniqKey="Martinowitz U">U Martinowitz</name>
</author>
<author><name sortKey="Lissitchkov, T" uniqKey="Lissitchkov T">T Lissitchkov</name>
</author>
<author><name sortKey="Lubetsky, A" uniqKey="Lubetsky A">A Lubetsky</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Verbruggen, B" uniqKey="Verbruggen B">B Verbruggen</name>
</author>
<author><name sortKey="Novakova, I" uniqKey="Novakova I">I Novakova</name>
</author>
<author><name sortKey="Wessels, H" uniqKey="Wessels H">H Wessels</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Windyga, J" uniqKey="Windyga J">J Windyga</name>
</author>
<author><name sortKey="Lissitchkov, T" uniqKey="Lissitchkov T">T Lissitchkov</name>
</author>
<author><name sortKey="Stasyshyn, O" uniqKey="Stasyshyn O">O Stasyshyn</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Morfini, M" uniqKey="Morfini M">M Morfini</name>
</author>
<author><name sortKey="Lee, M" uniqKey="Lee M">M Lee</name>
</author>
<author><name sortKey="Messori, A" uniqKey="Messori A">A. Messori</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lee, M" uniqKey="Lee M">M Lee</name>
</author>
<author><name sortKey="Morfini, M" uniqKey="Morfini M">M Morfini</name>
</author>
<author><name sortKey="Schulman, S" uniqKey="Schulman S">S Schulman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rallapalli, Pm" uniqKey="Rallapalli P">PM Rallapalli</name>
</author>
<author><name sortKey="Kemball Cook, G" uniqKey="Kemball Cook G">G Kemball-Cook</name>
</author>
<author><name sortKey="Tuddenham, Eg" uniqKey="Tuddenham E">EG Tuddenham</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Santagostino, E" uniqKey="Santagostino E">E Santagostino</name>
</author>
<author><name sortKey="Martinowitz, U" uniqKey="Martinowitz U">U Martinowitz</name>
</author>
<author><name sortKey="Lissitchkov, T" uniqKey="Lissitchkov T">T Lissitchkov</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Collins, Pw" uniqKey="Collins P">PW Collins</name>
</author>
<author><name sortKey="Young, G" uniqKey="Young G">G Young</name>
</author>
<author><name sortKey="Knobe, K" uniqKey="Knobe K">K Knobe</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Roth, Da" uniqKey="Roth D">DA. Roth</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Journeycake, Jm" uniqKey="Journeycake J">JM. Journeycake</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Price, Ve" uniqKey="Price V">VE Price</name>
</author>
<author><name sortKey="Carcao, M" uniqKey="Carcao M">M Carcao</name>
</author>
<author><name sortKey="Connolly, B" uniqKey="Connolly B">B Connolly</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ranta, S" uniqKey="Ranta S">S Ranta</name>
</author>
<author><name sortKey="Kalajoki Helmio, T" uniqKey="Kalajoki Helmio T">T Kalajoki-Helmiö</name>
</author>
<author><name sortKey="Pouttu, J" uniqKey="Pouttu J">J Pouttu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Blanchette, Vs" uniqKey="Blanchette V">VS Blanchette</name>
</author>
<author><name sortKey="Key, Ns" uniqKey="Key N">NS Key</name>
</author>
<author><name sortKey="Ljung, Lr" uniqKey="Ljung L">LR Ljung</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Goodeve, Ac" uniqKey="Goodeve A">AC Goodeve</name>
</author>
<author><name sortKey="Reitsma, Ph" uniqKey="Reitsma P">PH Reitsma</name>
</author>
<author><name sortKey="Mcvey, Jh" uniqKey="Mcvey J">JH. McVey</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Broderick, Cr" uniqKey="Broderick C">CR Broderick</name>
</author>
<author><name sortKey="Herbert, Rd" uniqKey="Herbert R">RD Herbert</name>
</author>
<author><name sortKey="Latimer, J" uniqKey="Latimer J">J. Latimer</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Thromb Haemost</journal-id>
<journal-id journal-id-type="iso-abbrev">Thromb. Haemost</journal-id>
<journal-id journal-id-type="publisher-id">TH</journal-id>
<journal-title-group><journal-title>Thrombosis and Haemostasis</journal-title>
</journal-title-group>
<issn pub-type="ppub">0340-6245</issn>
<publisher><publisher-name>Schattauer</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">27583313</article-id>
<article-id pub-id-type="pmc">5039316</article-id>
<article-id pub-id-type="doi">10.1160/TH16-03-0179</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Coagulation and Fibrinolysis</subject>
</subj-group>
</article-categories>
<title-group><article-title>Long-Acting Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) in Children</article-title>
<subtitle>Results of a Phase 3 Trial</subtitle>
</title-group>
<contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Kenet</surname>
<given-names>Gili</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor1"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chambost</surname>
<given-names>Hervé</given-names>
</name>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Male</surname>
<given-names>Christoph</given-names>
</name>
<xref ref-type="aff" rid="aff003"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lambert</surname>
<given-names>Thierry</given-names>
</name>
<xref ref-type="aff" rid="aff004"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Halimeh</surname>
<given-names>Susan</given-names>
</name>
<xref ref-type="aff" rid="aff005"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chernova</surname>
<given-names>Tatiana</given-names>
</name>
<xref ref-type="aff" rid="aff006"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mancuso</surname>
<given-names>Maria Elisa</given-names>
</name>
<xref ref-type="aff" rid="aff007"><sup>7</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Curtin</surname>
<given-names>Julie</given-names>
</name>
<xref ref-type="aff" rid="aff008"><sup>8</sup>
</xref>
<xref ref-type="aff" rid="aff009"><sup>9</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Voigt</surname>
<given-names>Christine</given-names>
</name>
<xref ref-type="aff" rid="aff010"><sup>10</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Li</surname>
<given-names>Yanyan</given-names>
</name>
<xref ref-type="aff" rid="aff010"><sup>10</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jacobs</surname>
<given-names>Iris</given-names>
</name>
<xref ref-type="aff" rid="aff010"><sup>10</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Santagostino</surname>
<given-names>Elena</given-names>
</name>
<xref ref-type="aff" rid="aff007"><sup>7</sup>
</xref>
</contrib>
<contrib contrib-type="author"><collab>the PROLONG-9FP Investigator Study Group</collab>
<xref ref-type="author-notes" rid="fn1"><sup>*</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff001"><label>1</label>
<institution>The Israeli National Hemophilia Center, Sheba Medical Center, tel Hashomer, Sackler Medical School</institution>
,<addr-line>tel Aviv University, Israel</addr-line>
</aff>
<aff id="aff002"><label>2</label>
Pediatric Hematology Oncology Department,<institution>Children Hospital La Timone, APHM, Aix Marseille University</institution>
,<addr-line>Marseille, France</addr-line>
</aff>
<aff id="aff003"><label>3</label>
Department of Pediatrics,<institution>Medical University of Vienna</institution>
,<addr-line>Vienna, Austria</addr-line>
</aff>
<aff id="aff004"><label>4</label>
<institution>Centre de Traitement des ’Hémophilies</institution>
,<addr-line>Hôpital Bicetre, Paris, France</addr-line>
</aff>
<aff id="aff005"><label>5</label>
<institution>CRC Coagulation Research Centre GmbH</institution>
,<addr-line>Duisburg, Germany</addr-line>
</aff>
<aff id="aff006"><label>6</label>
<institution>Kirov Research Institute of Hematology and Blood Transfusion</institution>
,<addr-line>Kirov, Russia</addr-line>
</aff>
<aff id="aff007"><label>7</label>
<institution>Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico</institution>
,<addr-line>Milan, Italy</addr-line>
</aff>
<aff id="aff008"><label>8</label>
<institution>Children’s Hospital at Westmead, Sydney Children’s Hospital Network</institution>
,<addr-line>Sydney, Australia</addr-line>
</aff>
<aff id="aff009"><label>9</label>
<institution>Discipline of Paediatrics and Child Health, University of Sydney</institution>
,<addr-line>Australia</addr-line>
</aff>
<aff id="aff010"><label>10</label>
<institution>CSL Behring, CRD, King of Prussia</institution>
,<addr-line>Pennsylvania, USA</addr-line>
</aff>
<author-notes><corresp id="cor1">Gili Kenet, The Israeli National Hemophilia Center, Sheba Medical Center tel Hashomer, Sackler Medical School, tel Aviv University, Israel, <phone>+972 3 5302950</phone>
, <fax>+972 3 5351806</fax>
, <email>gili.kenet@sheba.health.gov.il</email>
</corresp>
<fn id="fn1"><p>* Members of the PROLONG-9FP Investigator Study Group are listed in the Appendix.</p>
</fn>
<fn><p><bold>Financial support:</bold>
</p>
<p>This study was sponsored by CSL Behring, Marburg, Germany. Editorial assistance was provided by Meridian HealthComms, funded by CSL Behring.</p>
</fn>
</author-notes>
<pub-date pub-type="epub"><day>01</day>
<month>9</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="ppub"><day>27</day>
<month>9</month>
<year>2016</year>
</pub-date>
<volume>116</volume>
<issue>4</issue>
<fpage>659</fpage>
<lpage>668</lpage>
<history><date date-type="received"><day>03</day>
<month>3</month>
<year>2016</year>
</date>
<date date-type="accepted"><day>23</day>
<month>5</month>
<year>2016</year>
</date>
</history>
<permissions><copyright-statement>© The Authors 2016</copyright-statement>
<copyright-year>2016</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/"><license-p>This is an open access article under the terms of the Creative Commons License, wich permits use and distribution in any medium, provided the original work is properly cited and is not used for commercial purposes and no modifications or adaptations are made.</license-p>
</license>
</permissions>
<abstract><title>Summary</title>
<p>A global phase 3 study evaluated the pharmacokinetics, efficacy and safety of a recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 27 previously treated male children (1–11 years) with severe and moderately severe haemophilia B (factor IX [FIX] activity ≤2 IU/dl). All patients received routine prophylaxis once every seven days for up to 77 weeks, and treated any bleeding episodes on-demand. The mean terminal half-life of rIX-FP was 91.4 hours (h), 4.3-fold longer than previous FIX treatment and clearance was 1.11 ml/h/kg, 6.4-fold slower than previous FIX treatment. The median (Q1, Q3) annualised spontaneous bleeding rate was 0.00 (0.00, 0.91) and was similar between the <6 years and ≥6 years age groups, with a weekly median prophylactic dose of 46 IU/kg. In addition, patients maintained a median trough level of 13.4 IU/dl FIX activity on weekly prophylaxis. Overall, 97.2% of bleeding episodes were successfully treated with one or two injections of rIX-FP (95% CI: 92% to 99%), 88.7% with one injection, and 96% of the treatments were rated effective (excellent or good) by the Investigator. No patient developed FIX inhibitors and no safety concerns were identified. These results indicate that rIX-FP is safe and effective for preventing and treating bleeding episodes in children with haemophilia B with weekly prophylaxis. Routine prophylaxis with rIX-FP at treatment intervals of up to 14 days are currently being investigated in children with severe and moderately severe haemophilia B. Clinicaltrials.gov (NCT01662531)</p>
</abstract>
<kwd-group><title>Keywords</title>
<kwd>Haemophilia B</kwd>
<kwd>factor IX</kwd>
<kwd>on-demand treatment</kwd>
<kwd>prophylactic regimen</kwd>
<kwd>rIX-FP</kwd>
</kwd-group>
<counts><fig-count count="2"></fig-count>
<table-count count="5"></table-count>
<equation-count count="0"></equation-count>
<ref-count count="26"></ref-count>
<page-count count="10"></page-count>
</counts>
</article-meta>
</front>
<floats-group><fig id="fig001" orientation="portrait" position="float"><label>Figure 1:</label>
<caption><p><bold>Patient enrolment and study flow diagram.</bold>
The diagram shows the flow and disposition of patients in the study. Following screening, 27 patients were enrolled in the study. All patients participated in PK evaluation of 50 IU/kg rIX-FP. A subset of patients (n=17) also participated in a PK evaluation of their previous FIX product (pdFIX or rFIX). All patients were assigned weekly prophylaxis with a dose of 35–50 IU/kg. All patients completed the study. FIX, factor IX; pdFIX, plasma-derived FIX; PK, pharmacokinetics; rFIX, recombinant FIX; rIX-FP, recombinant fusion protein linking coagulation factor IX with albumin.</p>
</caption>
<graphic xlink:href="TH-116-04-16030179-g001"></graphic>
</fig>
<fig id="fig002" orientation="portrait" position="float"><label>Figure 2:</label>
<caption><p><bold>FIX activity after injection of a single dose of rIX-FP or previous FIX product (PK population).</bold>
Mean baseline-uncorrected FIX activity after administration of a single infusion of 50 IU/kg of rIX-FP or 50 IU/kg previous FIX product (pdFIX or rFIX). FIX activity was measured in IU/dl. Vertical bars represent standard deviation. FIX, factor IX; pdFIX, plasma-derived FIX; PK, pharmacokinetic; rFIX, recombinant FIX; rIX-FP, recombinant fusion protein linking coagulation factor IX with albumin.</p>
</caption>
<graphic xlink:href="TH-116-04-16030179-g002"></graphic>
</fig>
<table-wrap id="table001" orientation="portrait" position="float"><label>Table 1:</label>
<caption><p>Baseline demographics and patient characteristics.</p>
</caption>
<table frame="box" rules="all"><thead><tr><th align="left" valign="top" rowspan="1" colspan="1">Characteristics</th>
<th align="left" valign="top" rowspan="1" colspan="1"><6 years<break></break>
(N=12)</th>
<th align="left" valign="top" rowspan="1" colspan="1">6–11 years<break></break>
(N=15)</th>
<th align="left" valign="top" rowspan="1" colspan="1">Total<break></break>
(N=27)</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">Mean age (SD), years</td>
<td align="left" valign="top" rowspan="1" colspan="1">3.2 (1.70)</td>
<td align="left" valign="top" rowspan="1" colspan="1">8.1 (1.41)</td>
<td align="left" valign="top" rowspan="1" colspan="1">5.9 (2.93)</td>
</tr>
<tr><td align="left" valign="top" colspan="4" rowspan="1">Race, n (%)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> White</td>
<td align="left" valign="top" rowspan="1" colspan="1">11 (91.7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">15 (100.0)</td>
<td align="left" valign="top" rowspan="1" colspan="1">26 (96.3)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Black/African-American</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 (8.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">0</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 (3.7)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Mean weight (SD), kg</td>
<td align="left" valign="top" rowspan="1" colspan="1">16.0 (3.81)</td>
<td align="left" valign="top" rowspan="1" colspan="1">31.4 (9.73)</td>
<td align="left" valign="top" rowspan="1" colspan="1">24.6 (10.87)</td>
</tr>
<tr><td align="left" valign="top" colspan="4" rowspan="1">Geographic location, n (%)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Asia Pacific</td>
<td align="left" valign="top" rowspan="1" colspan="1">0</td>
<td align="left" valign="top" rowspan="1" colspan="1">2 (13.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">2 (7.4)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Europe</td>
<td align="left" valign="top" rowspan="1" colspan="1">9 (75.0)</td>
<td align="left" valign="top" rowspan="1" colspan="1">11 (73.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">20 (74.0)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Middle East</td>
<td align="left" valign="top" rowspan="1" colspan="1">2 (16.7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">2 (13.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">4 (14.8)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> North America</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 (8.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">0</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 (3.7)</td>
</tr>
<tr><td align="left" valign="top" colspan="4" rowspan="1">Previous treatment regimen</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> On-demand</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 (8.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">2 (13.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">3 (11.1)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Prophylaxis</td>
<td align="left" valign="top" rowspan="1" colspan="1">11 (91.7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">13 (86.7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">24 (88.9)</td>
</tr>
<tr><td align="left" valign="top" colspan="4" rowspan="1">Previous FIX product</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> rFIX</td>
<td align="left" valign="top" rowspan="1" colspan="1">10 (83.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">11 (73.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">21 (77.8)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> pdFIX</td>
<td align="left" valign="top" rowspan="1" colspan="1">2 (16.7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">4 (26.7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">6 (22.2)</td>
</tr>
<tr><td align="left" valign="top" colspan="4" rowspan="1">Previous prophylaxis interval, n (%)<xref ref-type="fn" rid="table001-tfn1">*</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> <2 times per week</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 (9.1)</td>
<td align="left" valign="top" rowspan="1" colspan="1">3 (23.1)</td>
<td align="left" valign="top" rowspan="1" colspan="1">4 (16.7)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> 2 times per week</td>
<td align="left" valign="top" rowspan="1" colspan="1">8 (72.7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">7 (53.8)</td>
<td align="left" valign="top" rowspan="1" colspan="1">15 (62.5)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> ≥3 times per week</td>
<td align="left" valign="top" rowspan="1" colspan="1">2 (18.2)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 (7.7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">3 (12.5)</td>
</tr>
<tr><td align="left" valign="top" colspan="4" rowspan="1">Previous FIX weekly consumption, IU/kg</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Mean (SD)</td>
<td align="left" valign="top" rowspan="1" colspan="1">138.7 (123.83)</td>
<td align="left" valign="top" rowspan="1" colspan="1">80.3 (47.25)</td>
<td align="left" valign="top" rowspan="1" colspan="1">107.1 (93.34)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Target joint <xref ref-type="fn" rid="table001-tfn2">†</xref>
, n (%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">2 (16.7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 (6.7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">3 (11.1)</td>
</tr>
<tr><td align="left" valign="top" colspan="4" rowspan="1">Total ABR <xref ref-type="fn" rid="table001-tfn3">‡</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Mean (SD)</td>
<td align="left" valign="top" rowspan="1" colspan="1">6.5 (9.98)</td>
<td align="left" valign="top" rowspan="1" colspan="1">7.4 (13.56)</td>
<td align="left" valign="top" rowspan="1" colspan="1">7.0 (11.89)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Median (IQR)</td>
<td align="left" valign="top" rowspan="1" colspan="1">3.0 (1.0, 4.5)</td>
<td align="left" valign="top" rowspan="1" colspan="1">2.0 (1.0, 6.0)</td>
<td align="left" valign="top" rowspan="1" colspan="1">3.0 (1.0, 6.0)</td>
</tr>
<tr><td align="left" valign="top" colspan="4" rowspan="1">AsBR <xref ref-type="fn" rid="table001-tfn3">‡</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Mean (SD)</td>
<td align="left" valign="top" rowspan="1" colspan="1">2.8 (5.11)</td>
<td align="left" valign="top" rowspan="1" colspan="1">4.9 (11.74)</td>
<td align="left" valign="top" rowspan="1" colspan="1">3.9 (9.18)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Median (IQR)</td>
<td align="left" valign="top" rowspan="1" colspan="1">0.5 (0.0, 2.5)</td>
<td align="left" valign="top" rowspan="1" colspan="1">0.0 (0.0, 1.0)</td>
<td align="left" valign="top" rowspan="1" colspan="1">0.0 (0.0, 2.0)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">History of catheter use, n (%)</td>
<td align="left" valign="top" rowspan="1" colspan="1">2 (16.7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 (6.7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">3 (11.1)</td>
</tr>
<tr><td align="left" valign="top" colspan="4" rowspan="1">Activity level, n (%)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Sedentary</td>
<td align="left" valign="top" rowspan="1" colspan="1">0</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 (6.6)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 (3.7)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Moderately active</td>
<td align="left" valign="top" rowspan="1" colspan="1">7 (58.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">6 (40.0)</td>
<td align="left" valign="top" rowspan="1" colspan="1">13 (48.1)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Vigorous</td>
<td align="left" valign="top" rowspan="1" colspan="1">5 (41.7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">8 (53.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">13 (48.1)</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>ABR, annualised bleeding rate; AsBR, annualised spontaneous bleeding rate; FIX, factor IX; IQR, interquartile range; pdFIX, plasma-derived factor IX; rIX, recombinant factor IX; SD, standard deviation.</p>
</fn>
<fn id="table001-tfn1"><p>*Percentages are based on the number of patients who received prophylaxis prior to study entry.</p>
</fn>
<fn id="table001-tfn2"><p>†Percentages are based on the number of patients with a target joint, defined as at least 3 spontaneous bleeding episodes in the same joint in a 6-month period (22).</p>
</fn>
<fn id="table001-tfn3"><p>‡Bleeding episodes in the 12 months prior to study entry.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="table002" orientation="portrait" position="float"><label>Table 2:</label>
<caption><p>Factor IX genotype of patients.</p>
</caption>
<table frame="box" rules="all"><thead><tr><th align="left" valign="top" colspan="2" rowspan="1">Mutation<xref ref-type="fn" rid="table002-tfn1">*</xref>
</th>
<th align="left" valign="top" rowspan="2" colspan="1">Previous reports<xref ref-type="fn" rid="table002-tfn2">†</xref>
</th>
<th align="left" valign="top" rowspan="2" colspan="1">Type of mutation</th>
</tr>
<tr><th align="left" valign="top" rowspan="1" colspan="1">cDNA</th>
<th align="left" valign="top" rowspan="1" colspan="1">AA/codon</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">c.711A>G</td>
<td align="left" valign="top" rowspan="1" colspan="1">Gln237Gln</td>
<td align="left" valign="top" rowspan="1" colspan="1">2</td>
<td align="left" valign="top" rowspan="1" colspan="1">Silent</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">c.136delA</td>
<td align="left" valign="top" rowspan="1" colspan="1">p.Arg46GlyfsX58</td>
<td align="left" valign="top" rowspan="1" colspan="1">0</td>
<td align="left" valign="top" rowspan="1" colspan="1">Deletion, frameshift</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">c.1279G>A</td>
<td align="left" valign="top" rowspan="1" colspan="1">Gly427Arg</td>
<td align="left" valign="top" rowspan="1" colspan="1">5</td>
<td align="left" valign="top" rowspan="1" colspan="1">Missense</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">c.1369A>T</td>
<td align="left" valign="top" rowspan="1" colspan="1">Lys457Stop</td>
<td align="left" valign="top" rowspan="1" colspan="1">1</td>
<td align="left" valign="top" rowspan="1" colspan="1">Nonsense</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">c.880C>T</td>
<td align="left" valign="top" rowspan="1" colspan="1">Arg294Stop</td>
<td align="left" valign="top" rowspan="1" colspan="1">70</td>
<td align="left" valign="top" rowspan="1" colspan="1">Nonsense</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">c.676C>T</td>
<td align="left" valign="top" rowspan="1" colspan="1">Arg226Trp</td>
<td align="left" valign="top" rowspan="1" colspan="1">44</td>
<td align="left" valign="top" rowspan="1" colspan="1">Missense</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">c.226G>A</td>
<td align="left" valign="top" rowspan="1" colspan="1">Glu76Lys</td>
<td align="left" valign="top" rowspan="1" colspan="1">3</td>
<td align="left" valign="top" rowspan="1" colspan="1">Missense</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">--</td>
<td align="left" valign="top" rowspan="1" colspan="1">Val377del</td>
<td align="left" valign="top" rowspan="1" colspan="1">6</td>
<td align="left" valign="top" rowspan="1" colspan="1">Deletion</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">c.128G>A</td>
<td align="left" valign="top" rowspan="1" colspan="1">Arg43Gln</td>
<td align="left" valign="top" rowspan="1" colspan="1">85</td>
<td align="left" valign="top" rowspan="1" colspan="1">Missense</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">c.871G>A</td>
<td align="left" valign="top" rowspan="1" colspan="1">Glu291Lys</td>
<td align="left" valign="top" rowspan="1" colspan="1">5</td>
<td align="left" valign="top" rowspan="1" colspan="1">Missense</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">c.830T>A</td>
<td align="left" valign="top" rowspan="1" colspan="1">Val277Asp</td>
<td align="left" valign="top" rowspan="1" colspan="1">1</td>
<td align="left" valign="top" rowspan="1" colspan="1">Missense</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">c.686G>T</td>
<td align="left" valign="top" rowspan="1" colspan="1">Gly229Val</td>
<td align="left" valign="top" rowspan="1" colspan="1">1<xref ref-type="fn" rid="table002-tfn3">‡</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">Missense</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="table002-tfn1"><p>* Nucleotide and codon numbering according to Human Genome Variation Society (HGVS) (23, 24), in which the first codon is the first residue (Met) of the 46-residue signal peptide/propeptide, and the first residue of the mature protein is 47.</p>
</fn>
<fn id="table002-tfn2"><p>† The number of patients reporting the mutation as captured in the Factor IX Variant Database, available at www.factorix.org. (13).</p>
</fn>
<fn id="table002-tfn3"><p>‡ Report of this mutation is in the CDC Hemophilia B Mutation Project (CHBMP) F9 Database only (25).</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="table003" orientation="portrait" position="float"><label>Table 3:</label>
<caption><p>Pharmacokinetic parameters of rIX-FP and previous FIX product in children with haemophilia B.</p>
</caption>
<table frame="box" rules="all"><thead><tr><th align="left" valign="top" rowspan="3" colspan="1">PK parameter (Unit)<xref ref-type="fn" rid="table003-tfn1">*</xref>
</th>
<th align="left" valign="top" colspan="3" rowspan="1">rIX–FP 50 IU/kg</th>
<th align="left" valign="top" colspan="3" rowspan="1">Previous FIX 50 IU/kg</th>
</tr>
<tr><th align="left" valign="top" rowspan="1" colspan="1"><6 years<break></break>
(N=12)</th>
<th align="left" valign="top" rowspan="1" colspan="1">6–11 years<break></break>
(N=15)</th>
<th align="left" valign="top" rowspan="1" colspan="1">Total<break></break>
(N=27)</th>
<th align="left" valign="top" rowspan="1" colspan="1"><6 years<break></break>
(N=8)</th>
<th align="left" valign="top" rowspan="1" colspan="1">6–11 years<break></break>
(N=9)</th>
<th align="left" valign="top" rowspan="1" colspan="1">Total<break></break>
(N=17)</th>
</tr>
<tr><th align="center" valign="top" colspan="6" rowspan="1">Mean (%CV)</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">IR (IU/dl)/(IU/kg)</td>
<td align="left" valign="top" rowspan="1" colspan="1">0.951 (21.5)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1.06 (22.6)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1.01 (22.5)</td>
<td align="left" valign="top" rowspan="1" colspan="1">0.676 (20.7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">0.793 (29.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">0.738 (26.8)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">AUC<sub>0-∞</sub>
(IU·h/dl)</td>
<td align="left" valign="top" rowspan="1" colspan="1">4583 (33.2)</td>
<td align="left" valign="top" rowspan="1" colspan="1">5123 (31.4)</td>
<td align="left" valign="top" rowspan="1" colspan="1">4894 (32.0)</td>
<td align="left" valign="top" rowspan="1" colspan="1">886 (70.1)</td>
<td align="left" valign="top" rowspan="1" colspan="1">890 (21.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">888 (46.9)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">t<sub>1/2</sub>
(h)</td>
<td align="left" valign="top" rowspan="1" colspan="1">89.6 (12.5)</td>
<td align="left" valign="top" rowspan="1" colspan="1">92.8 (20.5)</td>
<td align="left" valign="top" rowspan="1" colspan="1">91.4 (17.5)</td>
<td align="left" valign="top" rowspan="1" colspan="1">19.9 (40.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">17.7 (25.6)</td>
<td align="left" valign="top" rowspan="1" colspan="1">18.6 (33.0)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">CL (ml/h/kg) <xref ref-type="fn" rid="table003-tfn2">†</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">1.184 (27.8)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1.059 (28.5)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1.112 (28.2)</td>
<td align="left" valign="top" rowspan="1" colspan="1">7.158 (39.0)</td>
<td align="left" valign="top" rowspan="1" colspan="1">5.812 (23.7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">6.401 (33.5)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Vss (dl/kg) <xref ref-type="fn" rid="table003-tfn2">†</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">1.425 (24.1)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1.316 (19.7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1.362 (21.8)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1.765 (24.8)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1.431 (20.5)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1.577 (24.7)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">MRT (h)</td>
<td align="left" valign="top" rowspan="1" colspan="1">122.8 (14.2)</td>
<td align="left" valign="top" rowspan="1" colspan="1">129.2 (19.0)</td>
<td align="left" valign="top" rowspan="1" colspan="1">126.5 (17.1)</td>
<td align="left" valign="top" rowspan="1" colspan="1">27.7 (40.9)</td>
<td align="left" valign="top" rowspan="1" colspan="1">25.2 (21.2)</td>
<td align="left" valign="top" rowspan="1" colspan="1">26.3 (31.4)</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>AUC, area under the curve; CL, clearance; %CV, percent coefficient of variation; FIX, factor IX; IR, incremental recovery; MRT, mean residence time; PK, pharmacokinetic; rIX–FP, recombinant fusion protein linking coagulation factor IX with albumin; t<sub>1/2</sub>
, half–life; Vss, volume of distribution at steady–state.</p>
</fn>
<fn id="table003-tfn1"><p>* IR is baseline-corrected by FIX activity prior to dose.</p>
</fn>
<fn id="table003-tfn2"><p>† CL and Vss are normalised for body weight. Note: For rIX-FP, for the parameters of AUC<sub>0-∞</sub>
, t<sub>1/2</sub>
, CL, Vss, and MRT, the N for patients <6 years of age was 11, and total N was therefore 26. For previous FIX, for the parameters of AUC<sub>0-∞</sub>
, t<sub>1/2</sub>
, CL, Vss, and MRT, the N for patients <6 years of age was 7, and total N was therefore 16.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="table004" orientation="portrait" position="float"><label>Table 4:</label>
<caption><p>Annualised bleeding rates of children receiving once-weekly prophylaxis with rIX-FP.</p>
</caption>
<table frame="box" rules="all"><thead><tr><th rowspan="1" colspan="1"></th>
<th align="left" valign="top" rowspan="1" colspan="1"><6 years<break></break>
(N=12)</th>
<th align="left" valign="top" rowspan="1" colspan="1">6–11 years<break></break>
(N=15)</th>
<th align="left" valign="top" rowspan="1" colspan="1">Total<break></break>
(N=27)</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">Number of patients with ≥1 spontaneous bleeding episode, n (%)<xref ref-type="fn" rid="table004-tfn1">*</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">4 (33.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">9 (60.0)</td>
<td align="left" valign="top" rowspan="1" colspan="1">13 (48.1)</td>
</tr>
<tr><td align="left" valign="top" colspan="4" rowspan="1">AsBR <xref ref-type="fn" rid="table004-tfn2">†</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Median (IQR)</td>
<td align="left" valign="top" rowspan="1" colspan="1">0.00 (0.00, 0.00)</td>
<td align="left" valign="top" rowspan="1" colspan="1">0.78 (0.00, 1.99)</td>
<td align="left" valign="top" rowspan="1" colspan="1">0.00 (0.00, 0.91)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Estimated rate (95% CI) <xref ref-type="fn" rid="table004-tfn3">‡</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">0.09 (0.01, 0.58)</td>
<td align="left" valign="top" rowspan="1" colspan="1">0.86 (0.49, 1.51)</td>
<td align="left" valign="top" rowspan="1" colspan="1">0.56 (0.32, 1.00)</td>
</tr>
<tr><td align="left" valign="top" colspan="4" rowspan="1">Joint ABR <xref ref-type="fn" rid="table004-tfn2">†</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Median (IQR)</td>
<td align="left" valign="top" rowspan="1" colspan="1">0.50 (0.00, 1.45)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1.13 (0.00, 2.36)</td>
<td align="left" valign="top" rowspan="1" colspan="1">0.99 (0.00, 2.33)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Estimated rate (95% CI) <xref ref-type="fn" rid="table004-tfn3">‡</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">1.18 (0.50, 2.82)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1.60 (0.91, 2.84)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1.44 (0.89, 2.33)</td>
</tr>
<tr><td align="left" valign="top" colspan="4" rowspan="1">Total ABR <xref ref-type="fn" rid="table004-tfn2">†</xref>
</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Median (IQR)</td>
<td align="left" valign="top" rowspan="1" colspan="1">2.64 (2.00, 6.48)</td>
<td align="left" valign="top" rowspan="1" colspan="1">3.39 (0.76, 5.91)</td>
<td align="left" valign="top" rowspan="1" colspan="1">3.12 (0.91, 5.91)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Estimated rate (95% CI) <xref ref-type="fn" rid="table004-tfn3">‡</xref>
</td>
<td align="left" valign="top" rowspan="1" colspan="1">4.09 (2.66, 6.28)</td>
<td align="left" valign="top" rowspan="1" colspan="1">3.44 (2.13, 5.54)</td>
<td align="left" valign="top" rowspan="1" colspan="1">3.69 (2.65, 5.13)</td>
</tr>
<tr><td align="left" valign="top" colspan="4" rowspan="1">Time on study (days)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Median (IQR)</td>
<td align="left" valign="top" rowspan="1" colspan="1">356 (313.0, 373.5)</td>
<td align="left" valign="top" rowspan="1" colspan="1">456 (361.0, 492.0)</td>
<td align="left" valign="top" rowspan="1" colspan="1">382 (330.0, 469.0)</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>ABR, annualised bleeding rate; AsBR, annualised spontaneous bleeding rate; CI, confidence interval; IQR, interquartile range. The median (IQR) rIX-FP dose during the once-weekly prophylaxis regimen was 47.2 IU/kg (40.6, 55.8).</p>
</fn>
<fn id="table004-tfn1"><p>* Number of patients with ≥1 spontaneous bleeding episode during the course of the study.</p>
</fn>
<fn id="table004-tfn2"><p>† The ABR was defined as: 365.25 * (number of bleeding episodes) / (number of days in the observed treatment period of interest).</p>
</fn>
<fn id="table004-tfn3"><p>‡ The estimated rate was calculated assuming a Poisson distribution.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="table005" orientation="portrait" position="float"><label>Table 5:</label>
<caption><p>Summary of mild and moderate bleeding episodes and haemostatic response to rIX-FP.</p>
</caption>
<table frame="box" rules="all"><thead><tr><th rowspan="1" colspan="1"></th>
<th align="left" valign="top" rowspan="1" colspan="1"><6 years</th>
<th align="left" valign="top" rowspan="1" colspan="1">6–11 years</th>
<th align="left" valign="top" rowspan="1" colspan="1">Overall</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">Number of patients</td>
<td align="left" valign="top" rowspan="1" colspan="1">12</td>
<td align="left" valign="top" rowspan="1" colspan="1">15</td>
<td align="left" valign="top" rowspan="1" colspan="1">27</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Number of patients with bleeding episodes requiring treatment</td>
<td align="left" valign="top" rowspan="1" colspan="1">11</td>
<td align="left" valign="top" rowspan="1" colspan="1">12</td>
<td align="left" valign="top" rowspan="1" colspan="1">23</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Number of bleeding episodes requiring treatment</td>
<td align="left" valign="top" rowspan="1" colspan="1">45</td>
<td align="left" valign="top" rowspan="1" colspan="1">61</td>
<td align="left" valign="top" rowspan="1" colspan="1">106</td>
</tr>
<tr><td align="left" valign="top" colspan="4" rowspan="1">Type of bleeding episode, n (%)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Spontaneous</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 (2.2)</td>
<td align="left" valign="top" rowspan="1" colspan="1">15 (24.6)</td>
<td align="left" valign="top" rowspan="1" colspan="1">16 (15.1)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Traumatic</td>
<td align="left" valign="top" rowspan="1" colspan="1">38 (84.4)</td>
<td align="left" valign="top" rowspan="1" colspan="1">35 (57.4)</td>
<td align="left" valign="top" rowspan="1" colspan="1">73 (68.9)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Post-surgery</td>
<td align="left" valign="top" rowspan="1" colspan="1">0</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 (1.6)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 (0.9)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Unknown</td>
<td align="left" valign="top" rowspan="1" colspan="1">6 (13.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">10 (16.4)</td>
<td align="left" valign="top" rowspan="1" colspan="1">16 (15.1)</td>
</tr>
<tr><td align="left" valign="top" colspan="4" rowspan="1">Injections to treat a bleeding episode, n (%)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> 1 injection</td>
<td align="left" valign="top" rowspan="1" colspan="1">40 (88.9)</td>
<td align="left" valign="top" rowspan="1" colspan="1">54 (88.5)</td>
<td align="left" valign="top" rowspan="1" colspan="1">94 (88.7)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> 2 injections</td>
<td align="left" valign="top" rowspan="1" colspan="1">5 (11.1)</td>
<td align="left" valign="top" rowspan="1" colspan="1">4 (6.6)</td>
<td align="left" valign="top" rowspan="1" colspan="1">9 (8.5)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> >2 injections</td>
<td align="left" valign="top" rowspan="1" colspan="1">0</td>
<td align="left" valign="top" rowspan="1" colspan="1">3 (4.9)</td>
<td align="left" valign="top" rowspan="1" colspan="1">3 (2.8)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> 1 or 2 injections</td>
<td align="left" valign="top" rowspan="1" colspan="1">45 (100.0)</td>
<td align="left" valign="top" rowspan="1" colspan="1">58 (95.1)</td>
<td align="left" valign="top" rowspan="1" colspan="1">103 (97.2)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Probability of success<xref ref-type="fn" rid="table005-tfn1">*</xref>
, (95% CI)</td>
<td align="left" valign="top" rowspan="1" colspan="1">NC</td>
<td align="left" valign="top" rowspan="1" colspan="1">95.1 (86.7, 98.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">97.2 (92.0, 99.0)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1">Number of minor/ moderate bleeding episodes requiring treatment</td>
<td align="left" valign="top" rowspan="1" colspan="1">43</td>
<td align="left" valign="top" rowspan="1" colspan="1">61</td>
<td align="left" valign="top" rowspan="1" colspan="1">104</td>
</tr>
<tr><td align="left" valign="top" colspan="4" rowspan="1">Haemostatic response <xref ref-type="fn" rid="table005-tfn2">†</xref>
, n (%)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Excellent</td>
<td align="left" valign="top" rowspan="1" colspan="1">36 (83.7)</td>
<td align="left" valign="top" rowspan="1" colspan="1">42 (68.9)</td>
<td align="left" valign="top" rowspan="1" colspan="1">78 (75.0)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Good</td>
<td align="left" valign="top" rowspan="1" colspan="1">6 (14.0)</td>
<td align="left" valign="top" rowspan="1" colspan="1">16 (26.2)</td>
<td align="left" valign="top" rowspan="1" colspan="1">22 (21.2)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Moderate</td>
<td align="left" valign="top" rowspan="1" colspan="1">0</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 (1.6)</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 (1.0)</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Poor/No Response</td>
<td align="left" valign="top" rowspan="1" colspan="1">0</td>
<td align="left" valign="top" rowspan="1" colspan="1">0</td>
<td align="left" valign="top" rowspan="1" colspan="1">0</td>
</tr>
<tr><td align="left" valign="top" rowspan="1" colspan="1"> Missing</td>
<td align="left" valign="top" rowspan="1" colspan="1">1 (2.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">2 (3.3)</td>
<td align="left" valign="top" rowspan="1" colspan="1">3 (2.9)</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>CI, confidence interval; NC, not calculated.</p>
</fn>
<fn id="table005-tfn1"><p>* Probability of success is derived from a repeated measures model (expressed as percentages) and is defined as the probability of achieving haemostasis with 1 or 2 injections.</p>
</fn>
<fn id="table005-tfn2"><p>† Haemostatic response was evaluated by the physician. Definitions of haemostatic response for mild to moderate bleeding episodes: Excellent–pain relief and/or unequivocal improvement in objective signs of bleeding at approximately 24 hours after the first infusion and no additional infusions required in order to achieve haemostasis; Good–definite pain relief and/or improvement in signs of bleeding at approximately 24 hours after the first infusion, but required a second infusion in order to achieve haemostasis; Moderate–probable or slight beneficial effect at approximately 24 hours after the first infusion, and required more than 2 injections to achieve haemostasis; Poor/no response–no improvement or worsened at approximately 24 hours after the first infusion and additional haemostatic intervention required with other FIX product or plasma to achieve haemostasis.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>Autriche</li>
<li>France</li>
<li>Israël</li>
<li>Italie</li>
<li>Russie</li>
<li>États-Unis</li>
</country>
<region><li>Île-de-France</li>
</region>
<settlement><li>Paris</li>
</settlement>
</list>
<tree><country name="Israël"><noRegion><name sortKey="Kenet, Gili" sort="Kenet, Gili" uniqKey="Kenet G" first="Gili" last="Kenet">Gili Kenet</name>
</noRegion>
</country>
<country name="France"><noRegion><name sortKey="Chambost, Herve" sort="Chambost, Herve" uniqKey="Chambost H" first="Hervé" last="Chambost">Hervé Chambost</name>
</noRegion>
<name sortKey="Lambert, Thierry" sort="Lambert, Thierry" uniqKey="Lambert T" first="Thierry" last="Lambert">Thierry Lambert</name>
</country>
<country name="Autriche"><noRegion><name sortKey="Male, Christoph" sort="Male, Christoph" uniqKey="Male C" first="Christoph" last="Male">Christoph Male</name>
</noRegion>
</country>
<country name="Allemagne"><noRegion><name sortKey="Halimeh, Susan" sort="Halimeh, Susan" uniqKey="Halimeh S" first="Susan" last="Halimeh">Susan Halimeh</name>
</noRegion>
</country>
<country name="Russie"><noRegion><name sortKey="Chernova, Tatiana" sort="Chernova, Tatiana" uniqKey="Chernova T" first="Tatiana" last="Chernova">Tatiana Chernova</name>
</noRegion>
</country>
<country name="Italie"><noRegion><name sortKey="Mancuso, Maria Elisa" sort="Mancuso, Maria Elisa" uniqKey="Mancuso M" first="Maria Elisa" last="Mancuso">Maria Elisa Mancuso</name>
</noRegion>
<name sortKey="Santagostino, Elena" sort="Santagostino, Elena" uniqKey="Santagostino E" first="Elena" last="Santagostino">Elena Santagostino</name>
</country>
<country name="Australie"><noRegion><name sortKey="Curtin, Julie" sort="Curtin, Julie" uniqKey="Curtin J" first="Julie" last="Curtin">Julie Curtin</name>
</noRegion>
</country>
<country name="États-Unis"><noRegion><name sortKey="Voigt, Christine" sort="Voigt, Christine" uniqKey="Voigt C" first="Christine" last="Voigt">Christine Voigt</name>
</noRegion>
<name sortKey="Jacobs, Iris" sort="Jacobs, Iris" uniqKey="Jacobs I" first="Iris" last="Jacobs">Iris Jacobs</name>
<name sortKey="Li, Yanyan" sort="Li, Yanyan" uniqKey="Li Y" first="Yanyan" last="Li">Yanyan Li</name>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Pmc/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000805 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd -nk 000805 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Asie |area= AustralieFrV1 |flux= Pmc |étape= Checkpoint |type= RBID |clé= PMC:5039316 |texte= Long-Acting Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) in Children }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/RBID.i -Sk "pubmed:27583313" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd \ | NlmPubMed2Wicri -a AustralieFrV1
![]() | This area was generated with Dilib version V0.6.33. | ![]() |