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

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Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. / Scully, Marie; Knöbl, Paul; Kentouche, Karim; Rice, Lawrence; Windyga, Jerzy; Schneppenheim, Reinhard; Kremer Hovinga, Johanna A; Kajiwara, Michiko; Fujimura, Yoshihiro; Maggiore, Caterina; Doralt, Jennifer; Hibbard, Christopher; Martell, Leah; Ewenstein, Bruce.

In: BLOOD, Vol. 130, No. 19, 09.11.2017, p. 2055-2063.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Scully, M, Knöbl, P, Kentouche, K, Rice, L, Windyga, J, Schneppenheim, R, Kremer Hovinga, JA, Kajiwara, M, Fujimura, Y, Maggiore, C, Doralt, J, Hibbard, C, Martell, L & Ewenstein, B 2017, 'Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura', BLOOD, vol. 130, no. 19, pp. 2055-2063. https://doi.org/10.1182/blood-2017-06-788026

APA

Scully, M., Knöbl, P., Kentouche, K., Rice, L., Windyga, J., Schneppenheim, R., Kremer Hovinga, J. A., Kajiwara, M., Fujimura, Y., Maggiore, C., Doralt, J., Hibbard, C., Martell, L., & Ewenstein, B. (2017). Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. BLOOD, 130(19), 2055-2063. https://doi.org/10.1182/blood-2017-06-788026

Vancouver

Scully M, Knöbl P, Kentouche K, Rice L, Windyga J, Schneppenheim R et al. Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. BLOOD. 2017 Nov 9;130(19):2055-2063. https://doi.org/10.1182/blood-2017-06-788026

Bibtex

@article{b8294554d40346f49ed7d02051ccdba4,
title = "Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura",
abstract = "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.clinicaltrials.gov as #NCT02216084.",
keywords = "ADAMTS13 Protein, Adolescent, Adult, Dose-Response Relationship, Drug, Female, Humans, Male, Purpura, Thrombotic Thrombocytopenic, Recombinant Proteins, von Willebrand Factor, Clinical Trial, Phase I, Journal Article, Multicenter Study",
author = "Marie Scully and Paul Kn{\"o}bl and Karim Kentouche and Lawrence Rice and Jerzy Windyga and Reinhard Schneppenheim and {Kremer Hovinga}, {Johanna A} and Michiko Kajiwara and Yoshihiro Fujimura and Caterina Maggiore and Jennifer Doralt and Christopher Hibbard and Leah Martell and Bruce Ewenstein",
note = "{\textcopyright} 2017 by The American Society of Hematology.",
year = "2017",
month = nov,
day = "9",
doi = "10.1182/blood-2017-06-788026",
language = "English",
volume = "130",
pages = "2055--2063",
journal = "BLOOD",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "19",

}

RIS

TY - JOUR

T1 - Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura

AU - Scully, Marie

AU - Knöbl, Paul

AU - Kentouche, Karim

AU - Rice, Lawrence

AU - Windyga, Jerzy

AU - Schneppenheim, Reinhard

AU - Kremer Hovinga, Johanna A

AU - Kajiwara, Michiko

AU - Fujimura, Yoshihiro

AU - Maggiore, Caterina

AU - Doralt, Jennifer

AU - Hibbard, Christopher

AU - Martell, Leah

AU - Ewenstein, Bruce

N1 - © 2017 by The American Society of Hematology.

PY - 2017/11/9

Y1 - 2017/11/9

N2 - 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.clinicaltrials.gov as #NCT02216084.

AB - 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.clinicaltrials.gov as #NCT02216084.

KW - ADAMTS13 Protein

KW - Adolescent

KW - Adult

KW - Dose-Response Relationship, Drug

KW - Female

KW - Humans

KW - Male

KW - Purpura, Thrombotic Thrombocytopenic

KW - Recombinant Proteins

KW - von Willebrand Factor

KW - Clinical Trial, Phase I

KW - Journal Article

KW - Multicenter Study

U2 - 10.1182/blood-2017-06-788026

DO - 10.1182/blood-2017-06-788026

M3 - SCORING: Journal article

C2 - 28912376

VL - 130

SP - 2055

EP - 2063

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 19

ER -