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.
Level 2 - randomized trial
Double-blind randomized controlled phase I trial
PubMed 22568808 · doi:10.1111/j.1423-0410.2012.01603.x
What was done
A double-blind, dose-escalating phase I randomized controlled trial evaluated the safety and pharmacokinetics of roledumab, a recombinant human monoclonal anti-RhD antibody with optimized Fc glycosylation. Forty-six healthy RhD-negative volunteers received single intravenous doses ranging from 30 to 3000 μg of roledumab or placebo; 12 of these participants also received 300 μg intramuscularly. Participants were monitored for 6 months, and serum concentrations were measured using flow cytometry.
What was found
Fourteen treatment-related treatment-emergent adverse events occurred across 9 subjects, with no apparent difference in frequency or nature between roledumab and placebo. 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 μg i.v. The elimination half-life ranged from 18 to 22 days, and absolute intramuscular bioavailability was between 73% and 80%.
Why it matters
Roledumab demonstrates a half-life and pharmacokinetic profile similar to plasma-derived polyclonal anti-RhD immunoglobulin. This supports its potential as a recombinant alternative to prevent RhD alloimmunization without relying on donor-derived plasma.
Limits
The trial assessed only healthy volunteers following a single dose and did not test clearance of RhD-positive red blood cells or clinical efficacy. The sample size (n = 46) is too small to detect rare adverse events or low-incidence immunogenicity.
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