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
Version of Record online: 8 MAY 2012
© 2012 The Author(s). Vox Sanguinis © 2012 International Society of Blood Transfusion
Volume 103, Issue 3, pages 213–222, October 2012
How to Cite
Yver, A., Homery, M.-C., Fuseau, E., Guemas, E., Dhainaut, F., Quagliaroli, D., Beliard, R. and Prost, J.-F. (2012), 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, 103: 213–222. doi: 10.1111/j.1423-0410.2012.01603.x
- Issue online: 17 SEP 2012
- Version of Record online: 8 MAY 2012
- Received: 22 December 2011, revised: 25 January 2012, accepted: 16 February 2012
- antibody – function;
- clinical trial;
- recombinant proteins
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. AUClast increased from 4·4 ng/ml.day at 30 μg i.v. to 2257 ng/ml.day at 3000 g i.v. The t½ 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.