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

摘要

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 30-3000μg i.v. of roledumab or placebo using a double-blind escalating single-dose design; 12 of these subjects also received 300μg i.m. of roledumab. Subjects were followed for 6months 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 4·4ng/ml.day at 30μg i.v. to 2257ng/ml.day at 3000g i.v. The t 1/2 ranged from 18 to 22days, 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.