Danicopan : an oral complement factor D inhibitor for paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria (PNH) is characterised by complement-mediated intravascular hemolysis (IVH) due to absence of complement regulators CD55 and CD59 on affected erythrocytes. Danicopan is a first-in-class oral proximal, complement alternative pathway factor D (FD) inhibitor. Therapeutic FD inhibition was designed to control IVH and prevent C3-mediated extravascular hemolysis (EVH). In this open-label, phase 2, dose-finding trial, 10 untreated hemolytic PNH patients received danicopan monotherapy (100-200 mg thrice daily). Endpoints included change in lactate dehydrogenase (LDH) at day 28 (primary) and day 84 and hemoglobin. Safety, pharmacokinetics/pharmacodynamics, and patient-reported outcomes were measured. Ten patients reached the primary endpoint; two later discontinued: one for a serious adverse event (elevated aspartate aminotransferase/alanine aminotransferase coincident with breakthrough hemolysis, resolving without sequelae) and one for personal reasons unrelated to safety. Eight patients completed treatment. IVH was inhibited, demonstrated by mean decreased LDH (5.7 times upper limit of normal [ULN] at baseline vs 1.8 times ULN [day 28] and 2.2 times ULN [day 84]; both p.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:106 |
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| Enthalten in: |
Haematologica - 106(2021), 12 vom: 01. Dez., Seite 3188-3197 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Risitano, Antonio M [VerfasserIn] |
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| Links: |
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| Themen: |
9007-36-7 |
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| Anmerkungen: |
Date Completed 27.05.2021 Date Revised 04.04.2024 published: Electronic ClinicalTrials.gov: NCT03053102 Citation Status MEDLINE |
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| doi: |
10.3324/haematol.2020.261826 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM316897787 |
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| 500 | |a published: Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03053102 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Paroxysmal nocturnal hemoglobinuria (PNH) is characterised by complement-mediated intravascular hemolysis (IVH) due to absence of complement regulators CD55 and CD59 on affected erythrocytes. Danicopan is a first-in-class oral proximal, complement alternative pathway factor D (FD) inhibitor. Therapeutic FD inhibition was designed to control IVH and prevent C3-mediated extravascular hemolysis (EVH). In this open-label, phase 2, dose-finding trial, 10 untreated hemolytic PNH patients received danicopan monotherapy (100-200 mg thrice daily). Endpoints included change in lactate dehydrogenase (LDH) at day 28 (primary) and day 84 and hemoglobin. Safety, pharmacokinetics/pharmacodynamics, and patient-reported outcomes were measured. Ten patients reached the primary endpoint; two later discontinued: one for a serious adverse event (elevated aspartate aminotransferase/alanine aminotransferase coincident with breakthrough hemolysis, resolving without sequelae) and one for personal reasons unrelated to safety. Eight patients completed treatment. IVH was inhibited, demonstrated by mean decreased LDH (5.7 times upper limit of normal [ULN] at baseline vs 1.8 times ULN [day 28] and 2.2 times ULN [day 84]; both p | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Complement C3 |2 NLM | |
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| 700 | 1 | |a Lee, Jong Wook |e verfasserin |4 aut | |
| 700 | 1 | |a Maciejewski, Jaroslaw P |e verfasserin |4 aut | |
| 700 | 1 | |a Notaro, Rosario |e verfasserin |4 aut | |
| 700 | 1 | |a Brodsky, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Mingjun |e verfasserin |4 aut | |
| 700 | 1 | |a Geffner, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Browett, Peter |e verfasserin |4 aut | |
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