First-time-in-human study with GSK249320, a myelin-associated glycoprotein inhibitor, in healthy volunteers

Abstract

GSK249320, a monoclonal antibody directed against myelin-associated glycoprotein (MAG), is being developed for the enhancement of recovery of function poststroke. Potential safety concerns of adverse effects on myelin led to the inclusion of pharmacodynamic measures of peripheral and central neuronal function in this first-time-in-human (FTIH) study. The study also evaluated general safety, pharmacokinetics, and immunogenicity of GSK249320. Single intravenous infusions of GSK249320 (0.04, 0.4, 1.2, 3.5, 10, and 25 mg/kg) or placebo were administered to 47 healthy subjects aged 18-60 years. GSK249320 was well tolerated at all doses. No clinically significant abnormalities were observed in neurological examinations, nerve conduction tests (NCTs), quantitative sensory tests (QSTs), clinical laboratory tests, or electrocardiograms. There were no severe or serious adverse events. GSK249320 had a half-life (HL) of 21 days and a volume of distribution at steady state of 45.8 ml/kg, with AUC showing dose linearity. GSK249320 did not induce antidrug antibodies. © 2013 American Society for Clinical Pharmacology and Therapeutics.