Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency
Introduction Hereditary factor X (FX) deficiency is a rare bleeding disorder affecting 1:500 000 to 1:1 000 000 of individuals. Until recently, no specific replacement factor concentrate was available. Aim The aim of this study was to assess safety and efficacy of a new, high‐purity plasma‐derived F...
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| Veröffentlicht in: | Haemophilia : the official journal of the World Federation of Hemophilia 2016-05, Vol.22 (3), p.419-425 |
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| creator | Austin, S. K. Kavakli, K. Norton, M. Peyvandi, F. Shapiro, A. |
| description | Introduction
Hereditary factor X (FX) deficiency is a rare bleeding disorder affecting 1:500 000 to 1:1 000 000 of individuals. Until recently, no specific replacement factor concentrate was available.
Aim
The aim of this study was to assess safety and efficacy of a new, high‐purity plasma‐derived FX concentrate (pdFX) in subjects with hereditary FX deficiency.
Methods
Subjects aged ≥12 years with moderate or severe FX deficiency (plasma FX activity |
| doi_str_mv | 10.1111/hae.12893 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1808673928</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1790453152</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4593-84c0bbbe16badb2838b7150f96ec52edb732e72f24be25886c881878330ba32b3</originalsourceid><addsrcrecordid>eNqFkUtvEzEURi0Eog9Y8AeQJTZUYlo_xjOeZRXSFimCDa-dZXuuGaeJJ9gehaz46zikrRASwht7cb5j3fsh9IKSc1rOxaDhnDLZ8UfomPJGVEzQ5vH-LWglGW2O0ElKS0IoZ6R5io5YS7tWEnqMfs6d81bb3RuctIO8wzr0eDPouNZ2vPUBsrcJjw5rHGCLB_9tqDZT9IV02uYx4q_YjsFCyFFnwD7gNJkl2Jzw1ucBDxCh91nHPwI9lE89BLt7hp44vUrw_O4-RZ-u5h9nN9Xiw_W72eWisrXoeCVrS4wxQBuje8Mkl6algriuASsY9KblDFrmWG2ACSkbKyWVreScGM2Z4afo9cG7ieP3CVJWa58srFY6wDglRSWRTcu7ov4v2nakFpwKVtBXf6HLcYqhDKKYIB2r65rshWcHysYxpQhObaJfl4UoStS-QFUKVL8LLOzLO-Nk1tA_kPeNFeDiAGz9Cnb_Nqmby_m9sjokfMrw4yGh460qE7dCfXl_rRYzSa_o7LN6y38BW7WzdA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2509244408</pqid></control><display><type>article</type><title>Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Austin, S. K. ; Kavakli, K. ; Norton, M. ; Peyvandi, F. ; Shapiro, A.</creator><creatorcontrib>Austin, S. K. ; Kavakli, K. ; Norton, M. ; Peyvandi, F. ; Shapiro, A. ; FX Investigators Group ; the FX Investigators Group</creatorcontrib><description>Introduction
Hereditary factor X (FX) deficiency is a rare bleeding disorder affecting 1:500 000 to 1:1 000 000 of individuals. Until recently, no specific replacement factor concentrate was available.
Aim
The aim of this study was to assess safety and efficacy of a new, high‐purity plasma‐derived FX concentrate (pdFX) in subjects with hereditary FX deficiency.
Methods
Subjects aged ≥12 years with moderate or severe FX deficiency (plasma FX activity <5 IU dL−1) received 25 IU kg−1 pdFX as on‐demand treatment or short‐term prophylaxis for 6 months to 2 years. Subjects assessed pdFX efficacy for each bleed; at end‐of‐study, investigators assessed overall pdFX efficacy. Blood samples for pharmacokinetic analysis were obtained at baseline and ≥6 months. Safety was assessed by adverse events (AEs), inhibitor development and changes in laboratory parameters.
Results
Sixteen enrolled subjects (six aged 12–17 years; 10 aged 18–58 years) received a total of 468 pdFX infusions. In the 187 analysed bleeds, pdFX efficacy was categorized as excellent, good, poor or unassessable in 90.9%, 7.5%, 1.1% and 0.5% of bleeds respectively; 83% of bleeds were treated with one infusion. For pdFX, mean (median; interquartile range) incremental recovery and half‐life were 2.00 (2.12; 1.79–2.37) IU dL−1 per IU kg−1 and 29.4 (28.6; 25.8–33.1) h respectively. No serious AEs possibly related to pdFX or evidence of FX inhibitors were observed, and no hypersensitivity reactions or clinically significant trends were detected in laboratory parameters.
Conclusion
These results demonstrate that a dose of 25 IU kg−1 pdFX is safe and efficacious for on‐demand treatment and short‐term prophylaxis in subjects with moderate or severe hereditary FX deficiency.</description><identifier>ISSN: 1351-8216</identifier><identifier>EISSN: 1365-2516</identifier><identifier>DOI: 10.1111/hae.12893</identifier><identifier>PMID: 27197801</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Adolescent ; Adult ; Adverse events ; Antibodies, Neutralizing - blood ; Blood Coagulation Tests ; Child ; clinical trial ; clotting factor concentrate ; Coagulation factors ; efficacy ; Factor X - adverse effects ; Factor X - pharmacokinetics ; Factor X - therapeutic use ; factor X deficiency ; Factor X Deficiency - congenital ; Factor X Deficiency - drug therapy ; Factor X Deficiency - pathology ; Female ; Half-Life ; Hemorrhage - prevention & control ; Humans ; Hypersensitivity ; Laboratories ; Male ; Menorrhagia - prevention & control ; Middle Aged ; orphan drug ; Pharmacokinetics ; Prophylaxis ; Safety ; Severity of Illness Index ; Treatment Outcome ; Young Adult</subject><ispartof>Haemophilia : the official journal of the World Federation of Hemophilia, 2016-05, Vol.22 (3), p.419-425</ispartof><rights>2016 John Wiley & Sons Ltd</rights><rights>2016 John Wiley & Sons Ltd.</rights><rights>2020. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4593-84c0bbbe16badb2838b7150f96ec52edb732e72f24be25886c881878330ba32b3</citedby><cites>FETCH-LOGICAL-c4593-84c0bbbe16badb2838b7150f96ec52edb732e72f24be25886c881878330ba32b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fhae.12893$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fhae.12893$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27197801$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Austin, S. K.</creatorcontrib><creatorcontrib>Kavakli, K.</creatorcontrib><creatorcontrib>Norton, M.</creatorcontrib><creatorcontrib>Peyvandi, F.</creatorcontrib><creatorcontrib>Shapiro, A.</creatorcontrib><creatorcontrib>FX Investigators Group</creatorcontrib><creatorcontrib>the FX Investigators Group</creatorcontrib><title>Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency</title><title>Haemophilia : the official journal of the World Federation of Hemophilia</title><addtitle>Haemophilia</addtitle><description>Introduction
Hereditary factor X (FX) deficiency is a rare bleeding disorder affecting 1:500 000 to 1:1 000 000 of individuals. Until recently, no specific replacement factor concentrate was available.
Aim
The aim of this study was to assess safety and efficacy of a new, high‐purity plasma‐derived FX concentrate (pdFX) in subjects with hereditary FX deficiency.
Methods
Subjects aged ≥12 years with moderate or severe FX deficiency (plasma FX activity <5 IU dL−1) received 25 IU kg−1 pdFX as on‐demand treatment or short‐term prophylaxis for 6 months to 2 years. Subjects assessed pdFX efficacy for each bleed; at end‐of‐study, investigators assessed overall pdFX efficacy. Blood samples for pharmacokinetic analysis were obtained at baseline and ≥6 months. Safety was assessed by adverse events (AEs), inhibitor development and changes in laboratory parameters.
Results
Sixteen enrolled subjects (six aged 12–17 years; 10 aged 18–58 years) received a total of 468 pdFX infusions. In the 187 analysed bleeds, pdFX efficacy was categorized as excellent, good, poor or unassessable in 90.9%, 7.5%, 1.1% and 0.5% of bleeds respectively; 83% of bleeds were treated with one infusion. For pdFX, mean (median; interquartile range) incremental recovery and half‐life were 2.00 (2.12; 1.79–2.37) IU dL−1 per IU kg−1 and 29.4 (28.6; 25.8–33.1) h respectively. No serious AEs possibly related to pdFX or evidence of FX inhibitors were observed, and no hypersensitivity reactions or clinically significant trends were detected in laboratory parameters.
Conclusion
These results demonstrate that a dose of 25 IU kg−1 pdFX is safe and efficacious for on‐demand treatment and short‐term prophylaxis in subjects with moderate or severe hereditary FX deficiency.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Adverse events</subject><subject>Antibodies, Neutralizing - blood</subject><subject>Blood Coagulation Tests</subject><subject>Child</subject><subject>clinical trial</subject><subject>clotting factor concentrate</subject><subject>Coagulation factors</subject><subject>efficacy</subject><subject>Factor X - adverse effects</subject><subject>Factor X - pharmacokinetics</subject><subject>Factor X - therapeutic use</subject><subject>factor X deficiency</subject><subject>Factor X Deficiency - congenital</subject><subject>Factor X Deficiency - drug therapy</subject><subject>Factor X Deficiency - pathology</subject><subject>Female</subject><subject>Half-Life</subject><subject>Hemorrhage - prevention & control</subject><subject>Humans</subject><subject>Hypersensitivity</subject><subject>Laboratories</subject><subject>Male</subject><subject>Menorrhagia - prevention & control</subject><subject>Middle Aged</subject><subject>orphan drug</subject><subject>Pharmacokinetics</subject><subject>Prophylaxis</subject><subject>Safety</subject><subject>Severity of Illness Index</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>1351-8216</issn><issn>1365-2516</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtvEzEURi0Eog9Y8AeQJTZUYlo_xjOeZRXSFimCDa-dZXuuGaeJJ9gehaz46zikrRASwht7cb5j3fsh9IKSc1rOxaDhnDLZ8UfomPJGVEzQ5vH-LWglGW2O0ElKS0IoZ6R5io5YS7tWEnqMfs6d81bb3RuctIO8wzr0eDPouNZ2vPUBsrcJjw5rHGCLB_9tqDZT9IV02uYx4q_YjsFCyFFnwD7gNJkl2Jzw1ucBDxCh91nHPwI9lE89BLt7hp44vUrw_O4-RZ-u5h9nN9Xiw_W72eWisrXoeCVrS4wxQBuje8Mkl6algriuASsY9KblDFrmWG2ACSkbKyWVreScGM2Z4afo9cG7ieP3CVJWa58srFY6wDglRSWRTcu7ov4v2nakFpwKVtBXf6HLcYqhDKKYIB2r65rshWcHysYxpQhObaJfl4UoStS-QFUKVL8LLOzLO-Nk1tA_kPeNFeDiAGz9Cnb_Nqmby_m9sjokfMrw4yGh460qE7dCfXl_rRYzSa_o7LN6y38BW7WzdA</recordid><startdate>201605</startdate><enddate>201605</enddate><creator>Austin, S. K.</creator><creator>Kavakli, K.</creator><creator>Norton, M.</creator><creator>Peyvandi, F.</creator><creator>Shapiro, A.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201605</creationdate><title>Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency</title><author>Austin, S. K. ; Kavakli, K. ; Norton, M. ; Peyvandi, F. ; Shapiro, A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4593-84c0bbbe16badb2838b7150f96ec52edb732e72f24be25886c881878330ba32b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Adverse events</topic><topic>Antibodies, Neutralizing - blood</topic><topic>Blood Coagulation Tests</topic><topic>Child</topic><topic>clinical trial</topic><topic>clotting factor concentrate</topic><topic>Coagulation factors</topic><topic>efficacy</topic><topic>Factor X - adverse effects</topic><topic>Factor X - pharmacokinetics</topic><topic>Factor X - therapeutic use</topic><topic>factor X deficiency</topic><topic>Factor X Deficiency - congenital</topic><topic>Factor X Deficiency - drug therapy</topic><topic>Factor X Deficiency - pathology</topic><topic>Female</topic><topic>Half-Life</topic><topic>Hemorrhage - prevention & control</topic><topic>Humans</topic><topic>Hypersensitivity</topic><topic>Laboratories</topic><topic>Male</topic><topic>Menorrhagia - prevention & control</topic><topic>Middle Aged</topic><topic>orphan drug</topic><topic>Pharmacokinetics</topic><topic>Prophylaxis</topic><topic>Safety</topic><topic>Severity of Illness Index</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Austin, S. K.</creatorcontrib><creatorcontrib>Kavakli, K.</creatorcontrib><creatorcontrib>Norton, M.</creatorcontrib><creatorcontrib>Peyvandi, F.</creatorcontrib><creatorcontrib>Shapiro, A.</creatorcontrib><creatorcontrib>FX Investigators Group</creatorcontrib><creatorcontrib>the FX Investigators Group</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Haemophilia : the official journal of the World Federation of Hemophilia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Austin, S. K.</au><au>Kavakli, K.</au><au>Norton, M.</au><au>Peyvandi, F.</au><au>Shapiro, A.</au><aucorp>FX Investigators Group</aucorp><aucorp>the FX Investigators Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency</atitle><jtitle>Haemophilia : the official journal of the World Federation of Hemophilia</jtitle><addtitle>Haemophilia</addtitle><date>2016-05</date><risdate>2016</risdate><volume>22</volume><issue>3</issue><spage>419</spage><epage>425</epage><pages>419-425</pages><issn>1351-8216</issn><eissn>1365-2516</eissn><abstract>Introduction
Hereditary factor X (FX) deficiency is a rare bleeding disorder affecting 1:500 000 to 1:1 000 000 of individuals. Until recently, no specific replacement factor concentrate was available.
Aim
The aim of this study was to assess safety and efficacy of a new, high‐purity plasma‐derived FX concentrate (pdFX) in subjects with hereditary FX deficiency.
Methods
Subjects aged ≥12 years with moderate or severe FX deficiency (plasma FX activity <5 IU dL−1) received 25 IU kg−1 pdFX as on‐demand treatment or short‐term prophylaxis for 6 months to 2 years. Subjects assessed pdFX efficacy for each bleed; at end‐of‐study, investigators assessed overall pdFX efficacy. Blood samples for pharmacokinetic analysis were obtained at baseline and ≥6 months. Safety was assessed by adverse events (AEs), inhibitor development and changes in laboratory parameters.
Results
Sixteen enrolled subjects (six aged 12–17 years; 10 aged 18–58 years) received a total of 468 pdFX infusions. In the 187 analysed bleeds, pdFX efficacy was categorized as excellent, good, poor or unassessable in 90.9%, 7.5%, 1.1% and 0.5% of bleeds respectively; 83% of bleeds were treated with one infusion. For pdFX, mean (median; interquartile range) incremental recovery and half‐life were 2.00 (2.12; 1.79–2.37) IU dL−1 per IU kg−1 and 29.4 (28.6; 25.8–33.1) h respectively. No serious AEs possibly related to pdFX or evidence of FX inhibitors were observed, and no hypersensitivity reactions or clinically significant trends were detected in laboratory parameters.
Conclusion
These results demonstrate that a dose of 25 IU kg−1 pdFX is safe and efficacious for on‐demand treatment and short‐term prophylaxis in subjects with moderate or severe hereditary FX deficiency.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>27197801</pmid><doi>10.1111/hae.12893</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adolescent Adult Adverse events Antibodies, Neutralizing - blood Blood Coagulation Tests Child clinical trial clotting factor concentrate Coagulation factors efficacy Factor X - adverse effects Factor X - pharmacokinetics Factor X - therapeutic use factor X deficiency Factor X Deficiency - congenital Factor X Deficiency - drug therapy Factor X Deficiency - pathology Female Half-Life Hemorrhage - prevention & control Humans Hypersensitivity Laboratories Male Menorrhagia - prevention & control Middle Aged orphan drug Pharmacokinetics Prophylaxis Safety Severity of Illness Index Treatment Outcome Young Adult |
| title | Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency |
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