{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:44:04Z","timestamp":1790837044534,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T00:00:00Z","timestamp":1661212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    A phase 1b\/2, three\u2010month study of marstacimab, a human monoclonal antibody targeting tissue factor pathway inhibitor (TFPI), was conducted in participants with haemophilia A or B, with or without inhibitors. Participants assigned to four cohorts received escalating weekly doses based on inhibitor status (without inhibitors: 300\u2009mg, a single 300\u2010mg loading dose with subsequent 150\u2010mg doses, or 450\u2009mg; with inhibitors: 300\u2009mg). Safety outcomes were treatment\u2010emergent adverse events (TEAEs), injection site reactions, clinical and laboratory parameter changes. Efficacy was assessed by annualised bleeding rates (ABRs). Pharmacokinetics and pharmacodynamics (PD) were also evaluated. Among 26 treated participants [haemophilia A without inhibitor,\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a016 (61.5%); haemophilia A with inhibitor,\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a07 (26.9%); haemophilia B,\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a03 (11.5%)], 24 completed the study. Overall, 80.8% experienced TEAEs. ABR during treatment was significantly reduced\n                    <jats:italic>versus<\/jats:italic>\n                    an external on\u2010demand control group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) and\n                    <jats:italic>versus<\/jats:italic>\n                    pretreatment ABR (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001), with significant reductions observed across all dose cohorts. Marstacimab exposure generally increased in a dose\u2010related manner, with steady\u2010state concentration reached by day 57. Changes in pharmacodynamic biomarkers occurred across all dose cohorts. Marstacimab was safe and well tolerated. Clinically meaningful reductions in ABR and treatment\u2010related changes for all PD biomarkers indicated effective targeting of TFPI. (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">Clinicaltrials.gov<\/jats:ext-link>\n                    identifier, NCT02974855).\n                  <\/jats:p>","DOI":"10.1111\/bjh.18420","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T21:04:10Z","timestamp":1661288650000},"page":"229-239","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["A phase 1b\/2 clinical study of marstacimab, targeting human tissue factor pathway inhibitor, in haemophilia"],"prefix":"10.1111","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5781-7669","authenticated-orcid":false,"given":"Johnny N.","family":"Mahlangu","sequence":"first","affiliation":[{"name":"University of the Witwatersrand  Johannesburg South Africa"},{"name":"National Health Laboratory Service  Johannesburg South Africa"},{"name":"Charlotte Maxeke Johannesburg Academic Hospital  Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Luis","family":"Lamas","sequence":"additional","affiliation":[{"name":"Hospital Dr. S\u00f3tero del R\u00edo  Puente Alto Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Cristobal","family":"Morales","sequence":"additional","affiliation":[{"name":"Hospital Dr. S\u00f3tero del R\u00edo  Puente Alto Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R.","family":"Malan","sequence":"additional","affiliation":[{"name":"Phoenix Pharma, Mount Croix  Port Elizabeth South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silva Zupan\u010di\u0107","family":"\u0160alek","sequence":"additional","affiliation":[{"name":"University Hospital Centre Zagreb  Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Wang","sequence":"additional","affiliation":[{"name":"University of Colorado Hemophilia and Thrombosis Center  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa N.","family":"Boggio","sequence":"additional","affiliation":[{"name":"Rush Hemophilia and Thrombophilia Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"Hegemann","sequence":"additional","affiliation":[{"name":"Haemophilia Comprehensive Care Center University Hospital  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Mital","sequence":"additional","affiliation":[{"name":"Medical University of Gda\u0144sk  Gda\u0144sk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Cardinal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research and Development  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengling","family":"Sun","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research and Development  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Arkin","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research and Development  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.7326\/M19-1208"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14046"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12344"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067659"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01791.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01843.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01526.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2001.00534.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2012.02756.x"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12438"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.02828.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-08-742312"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-11-512764"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.2741\/3926"},{"key":"e_1_2_10_16_1","unstructured":"World Medical Association.WMA Declaration of Helsinki \u2010 Ethical Principles for Medical Research Involving Human Subjects.2013. [Accessed: November 14 2020]. Available from:https:\/\/www.wma.net\/policies\u2010post\/wma\u2010declaration\u2010of\u2010helsinki\u2010ethical\u2010principles\u2010for\u2010medical\u2010research\u2010involving\u2010human\u2010subjects\/"},{"key":"e_1_2_10_17_1","unstructured":"International Council for Harmonisation Working Group.ICH Harmonised Tripartite Guideline: Guideline for Good Clinical Practice E6(R1).1996. [Accessed: November 14 2020]. Available from:https:\/\/www.ich.org\/page\/efficacy\u2010guidelines"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14207"},{"key":"e_1_2_10_19_1","unstructured":"Division of Microbiology and Infectious Diseases (DMID)Adult Toxicity Table.2007. [Accessed: March 9 2020]. Available from:https:\/\/www.niaid.nih.gov\/sites\/default\/files\/dmidadulttox.pdf"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH14-09-0760"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12878"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.08.001"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43441-019-00014-4"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04611.x"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-10-529974"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13655"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1511769"},{"key":"e_1_2_10_28_1","first-page":"479","article-title":"Factor VIII replacement is still the standard of care in haemophilia A","volume":"17","author":"Aledort L","year":"2019","journal-title":"Blood Transfus"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/2040620717721458"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/13696998.2019.1620246"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019001542"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1871"},{"key":"e_1_2_10_33_1","unstructured":"FigueiredoM.Novo Nordisk pauses 3 clinical trials of concizumab amid safety concerns.2020. [Accessed: May 4 2021]. Available from:https:\/\/hemophilianewstoday.com\/2020\/03\/18\/novo\u2010nordisk\u2010pauses\u2010three\u2010clinical\u2010trials\u2010of\u2010concizumab\u2010due\u2010to\u2010safety\u2010concerns\/"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-143560"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000849"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1703068"},{"key":"e_1_2_10_37_1","unstructured":"Novo Nordisk pauses the clinical trials investigating concizumab (anti\u2010TFPI mAB) in haemophilia A and B with or without inhibitors [press release].2020. [Accessed: October 20 2020]. Available from:https:\/\/www.globenewswire.com\/news\u2010release\/2020\/03\/16\/2001361\/0\/en\/Novo\u2010Nordisk\u2010pauses\u2010the\u2010clinical\u2010trials\u2010investigating\u2010concizumab\u2010anti\u2010TFPI\u2010mAB\u2010in\u2010haemophilia\u2010A\u2010and\u2010B\u2010with\u2010or\u2010without\u2010inhibitors.html"},{"key":"e_1_2_10_38_1","unstructured":"Alnylam provides pipeline update on fitusiran and givosiran investigational RNAi therapeutic programs [press release].2017. [Accessed: October 20 2020]. Available from:https:\/\/investors.alnylam.com\/press\u2010release?id=21846"},{"key":"e_1_2_10_39_1","unstructured":"LimCN ZhuT DuaP.Use of pharmacokinetics\u2010pharmacodynamics modeling and simulation to support early phase dose selection for PF\u201006741086 an anti\u2010TFPI monoclonal antibody [poster]. Presented at: ACOP 10 the American Conference on Pharmacometrics; October 20\u201323 2018; Orlando FL."}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.18420","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bjh.18420","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.18420","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T01:53:55Z","timestamp":1692410035000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.18420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,23]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1111\/bjh.18420"],"URL":"https:\/\/doi.org\/10.1111\/bjh.18420","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,23]]},"assertion":[{"value":"2022-01-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}