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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
Author(s) -
Yver A.,
Homery M.C.,
Fuseau E.,
Guemas E.,
Dhainaut F.,
Quagliaroli D.,
Beliard R.,
Prost J.F.
Publication year - 2012
Publication title -
vox sanguinis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.68
H-Index - 83
eISSN - 1423-0410
pISSN - 0042-9007
DOI - 10.1111/j.1423-0410.2012.01603.x
Subject(s) - pharmacokinetics , medicine , antibody , bioavailability , adverse effect , monoclonal antibody , placebo , recombinant dna , polyclonal antibodies , pharmacology , monoclonal , immunology , chemistry , pathology , biochemistry , alternative medicine , gene
Background and Objectives 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. Materials and Methods 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. Results 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%. Conclusion Roledumab is safe and well tolerated in healthy RhD‐negative volunteers and shows a pharmacokinetic profile similar to that of polyclonal anti‐RhD immunoglobulin.