Recombinant ADAMTS-13: First-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura

Marie Scully, Paul Knöbl, Karim Kentouche, Lawrence Rice, Jerzy Windyga, Reinhard Schneppenheim, Johanna A. Kremer Hovinga, Michiko Kajiwara, Yoshihiro Fujimura, Caterina Maggiore, Jennifer Doralt, Christopher Hibbard, Leah Martell, Bruce Ewenstein

Research output: Contribution to journalArticlepeer-review

111 Scopus citations


Safety, tolerability, and pharmacokinetics of recombinant ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 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. After 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 maximum plasma concentration (Cmax [U/mL]) and area under the concentration–time curve (AUC [h∙U/mL]). 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 von Willebrand factor (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. This study was registered at www. as #NCT02216084.

Original languageEnglish (US)
Pages (from-to)2055-2063
Number of pages9
Issue number19
StatePublished - Nov 9 2017

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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