title: 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.
abstract: OBJECTIVE
  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.
  
  
  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%.
  
  
  CONCLUSIONS
  Roledumab is safe and well tolerated in healthy RhD-negative volunteers and shows a pharmacokinetic profile similar to that of polyclonal anti-RhD immunoglobulin.
authors.affiliation: LFB Biotechnologies, Les Ulis, France             Biotrial, Rennes, France             EMF Consulting, Les Milles, France.
authors.forename: A
authors.initials: A
authors.lastname: Yver
authors.forename: M-C
authors.initials: MC
authors.lastname: Homery
authors.forename: E
authors.initials: E
authors.lastname: Fuseau
authors.forename: E
authors.initials: E
authors.lastname: Guemas
authors.forename: F
authors.initials: F
authors.lastname: Dhainaut
authors.forename: D
authors.initials: D
authors.lastname: Quagliaroli
authors.forename: R
authors.initials: R
authors.lastname: Beliard
authors.forename: J-F
authors.initials: JF
authors.lastname: Prost
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000493:pharmacokinetics; D012204:Rh-Hr Blood-Group System / Q000276:immunology*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D007141:Immunoglobulin Fc Fragments; D017452:Receptors, IgG; D011994:Recombinant Proteins; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen