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dc.contributor.authorAmy D. Shapiroen_US
dc.contributor.authorPantep Angchaisuksirien_US
dc.contributor.authorJan Astermarken_US
dc.contributor.authorGary Bensonen_US
dc.contributor.authorGiancarlo Castamanen_US
dc.contributor.authorPratima Chowdaryen_US
dc.contributor.authorHermann Eichleren_US
dc.contributor.authorVictor Jiménez-Yusteen_US
dc.contributor.authorKaan Kavaklien_US
dc.contributor.authorTadashi Matsushitaen_US
dc.contributor.authorLone Hvitfeldt Poulsenen_US
dc.contributor.authorAllison P. Wheeleren_US
dc.contributor.authorGuy Youngen_US
dc.contributor.authorSilva Zupancic-Saleken_US
dc.contributor.authorJohannes Oldenburgen_US
dc.contributor.otherVanderbilt University Medical Centeren_US
dc.contributor.otherUniversitäts-Klinikum Bonn und Medizinische Fakultäten_US
dc.contributor.otherBelfast Health and Social Care Trusten_US
dc.contributor.otherAarhus Universiteten_US
dc.contributor.otherNHS Foundation Trusten_US
dc.contributor.otherHospital Universitario La Pazen_US
dc.contributor.otherNagoya University Hospitalen_US
dc.contributor.otherUniversitätsklinikum des Saarlandes Medizinische Fakultät der Universität des Saarlandesen_US
dc.contributor.otherEge Üniversitesien_US
dc.contributor.otherAzienda Ospedaliera Careggien_US
dc.contributor.otherJosip Juraj Strossmayer University of Osijeken_US
dc.contributor.otherFaculty of Medicine, Ramathibodi Hospital, Mahidol Universityen_US
dc.contributor.otherKeck School of Medicine of USCen_US
dc.contributor.otherSkånes universitetssjukhusen_US
dc.contributor.otherUniversity of Zagreb School of Medicineen_US
dc.contributor.otherIndiana Hemophilia and Thrombosis Centeren_US
dc.identifier.citationBlood. Vol.134, No.22 (2019), 1973-1982en_US
dc.description.abstract© 2019 by The American Society of Hematology. Results from the main parts (24 weeks) of 2 concizumab phase 2 trials are presented: explorer4 in hemophilia A (HA) or B (HB) with inhibitors (HAwI/HBwI) and explorer5 in HA. The trials aimed to evaluate the efficacy of daily subcutaneous concizumab prophylaxis (evaluated as annualized bleeding rate [ABR] at last dose level), with secondary objectives being safety and immunogenicity (assessed as number of adverse events [AEs] and antidrug antibodies [ADAs]). Patients received 0.15 mg/kg concizumab, with potential dose escalation to 0.20 and 0.25 mg/kg (if ‡3 spontaneous bleeding episodes within 12 weeks of concizumab treatment). Relevant pharmacokinetic/pharmacodynamic (PK/PD) parameters were assessed. Thirty-six HA, 9 HAwI, and 8 HBwI patients were exposed to concizumab. Most inhibitor patients (15 of 17; 88.2%) did not escalate the dose; all patients chose to continue to the extension phase of the trials. Clinical proof of concept for prevention of bleeding episodes was demonstrated in both trials. Estimated ABRs in HAwI and HBwI were lower vs HA: 3.0 (95% confidence interval [CI], 1.7; 5.3) and 5.9 (95% CI, 4.2; 8.5) vs 7.0 (95% CI, 4.6; 10.7), respectively. PK/PD results were as expected, with no difference between hemophilia subtypes for concizumab exposure, free tissue factor pathway inhibitor, thrombin generation, prothrombin fragment 112, and D-dimers. Concizumab was safe and well tolerated (no severe AEs, AE-related withdrawals, or thromboembolic events). Three patients had (very low to medium titer) ADA1 tests in each trial, with no observed clinical effect. These results support further development of concizumab as a daily prophylactic treatment in all hemophilia patients.en_US
dc.rightsMahidol Universityen_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.subjectImmunology and Microbiologyen_US
dc.titleSubcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors: Phase 2 trial resultsen_US
Appears in Collections:Scopus 2019

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