A recombinant human ADAMTS-13: first-in-human study evaluating pharmacokinetics, safety and tolerability in cTTP patients.

Scully, Marie; Knöbl, Paul; Kentouche, Karim; Rice, Lawrence; Windyga, Jerzy; Schneppenheim, Reinhard; Kremer Hovinga, Johanna Anna; Kajiwara, Michiko; Fujimura, Yoshihiro; Maggiore, Caterina; Doralt, Jennifer; Hibbard, Christopher; Martell, Leah; Ewenstein, Bruce (2017). A recombinant human ADAMTS-13: first-in-human study evaluating pharmacokinetics, safety and tolerability in cTTP patients. Blood, 130(19), pp. 2055-2063. American Society of Hematology 10.1182/blood-2017-06-788026

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Safety, tolerability and pharmacokinetics of recombinant ADAMTS-13 (rADAMTS-13; BAX 930; SHP655) were investigated in 15 patients diagnosed with severe congenital ADAMTS-13 deficiency (plasma ADAMTS-13 activity < 6%) in a prospective phase 1, first-in-human, multicenter dose escalation study. BAX 930 was well tolerated, no serious adverse events occurred, and no anti-ADAMTS-13 antibodies were observed. Following single dose administration of BAX 930 at 5, 20, or 40 U/kg body weight to adolescents and adults, there was approximate dose proportionality with respect to Cmax and AUC. Dose related increases of individual ADAMTS-13:Ag and activity were observed and reached a maximum within 1 hour. With escalating BAX 930 doses administered, a dose-dependent persistence of ADAMTS-13 mediated VWF cleavage products and reduced VWF multimeric size were observed. This study demonstrated that pharmacokinetic parameters of BAX 930 were comparable to those estimated in previous plasma infusion studies and provided evidence of pharmacodynamic activity. The study was registered on www.clinicaltrials.gov under the number NCT02216084.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)

UniBE Contributor:

Kremer Hovinga, Johanna Anna

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0006-4971

Publisher:

American Society of Hematology

Language:

English

Submitter:

Katrin Kölliker-Schütz

Date Deposited:

11 Dec 2017 08:48

Last Modified:

24 Oct 2019 06:39

Publisher DOI:

10.1182/blood-2017-06-788026

PubMed ID:

28912376

BORIS DOI:

10.7892/boris.106227

URI:

https://boris.unibe.ch/id/eprint/106227

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