Pharmacokinetics and safety of roledumab, a novel human recombinant monoclonal anti-RhD antibody with an optimized Fc for improved engagement of FCγRIII, in healthy volunteers

Vox Sanguinis
A YverJ-F Prost

Abstract

A human recombinant monoclonal anti-RhD IgG may be useful to prevent RhD allo-immunization. Roledumab is such an antibody with a glycosylation pattern optimized for biological activity. The objective of the study was to assess the safety and pharmacokinetics of roledumab in healthy RhD-negative volunteers. A total of 46 subjects received doses of 30-3000 μg i.v. of roledumab or placebo using a double-blind escalating single-dose design; 12 of these subjects also received 300 μg i.m. of roledumab. Subjects were followed for 6 months after administration. Serum roledumab concentrations were determined using flow cytometry. Fourteen treatment-emergent adverse events related to treatment were reported in nine subjects, with no apparent difference in their frequency or nature after placebo or roledumab administration. No anti-roledumab antibodies were detected. AUC(last) increased from 4·4 ng/ml.day at 30 μg i.v. to 2257 ng/ml.day at 3000 g i.v. The t(½) ranged from 18 to 22 days, and the absolute bioavailability after i.m. administration was between 73% and 80%. Roledumab is safe and well tolerated in healthy RhD-negative volunteers and shows a pharmacokinetic profile similar to that of polyclonal anti-RhD immunoglobulin.

References

May 1, 1968·Transfusion·W PollackW J Baker
May 11, 2000·Blood Reviews·S J Urbaniak, M A Greiss
Mar 15, 2001·Journal of Pharmaceutical and Biomedical Analysis·Y Vander HeydenD L Massart
Oct 31, 2001·Pharmaceutical Research·K J MillerR S Weiner
Mar 14, 2002·Transfusion clinique et biologique : journal de la Société française de transfusion sanguine·M Scott
Mar 14, 2002·Transfusion clinique et biologique : journal de la Société française de transfusion sanguine·Belinda M Kumpel
Dec 31, 2002·BJOG : an International Journal of Obstetrics and Gynaecology·Johann BichlerIrmgard Andresen
Aug 23, 2005·Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis·Petra Jilma-StohlawetzBernd Jilma
Dec 8, 2005·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Sophie SibérilJean-Luc Teillaud
Apr 4, 2006·Transfusion clinique et biologique : journal de la Société française de transfusion sanguine·R Béliard
Aug 16, 2006·The New England Journal of Medicine·Ganesh SuntharalingamNicki Panoskaltsis
Mar 6, 2007·Biotechnology Advances·Basant Sharma
Jan 12, 2010·Pharmaceuticals·Riad Abès, Jean-Luc Teillaud

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Citations

Jan 28, 2014·Biochemistry. Biokhimii︠a︡·D Quagliaroli
Aug 15, 2014·Transfusion Medicine·M de HaasD J Roberts
Dec 15, 2016·MAbs·Janice M Reichert
Jul 26, 2017·Obstetrics and Gynecology·UNKNOWN Committee on Practice Bulletins-Obstetrics
Dec 24, 2013·F1000Research·André WinklerMarc Ehlers
May 4, 2017·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Xiaojie YuMax Crispin
Mar 28, 2019·Annual Review of Biochemistry·Lai-Xi WangTiezheng Li
Sep 1, 2018·The Lancet Child & Adolescent Health·Alvin ZipurskyIsaac Odame

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