BACKGROUND AND PURPOSE: One class of poststroke restorative therapy focuses on promoting axon outgrowth by blocking myelin-based inhibitory proteins such as @entity10838 . The purpose of the current study was to extend preclinical and clinical findings of GSK249320, a humanized monoclonal antibody to @entity10838 with disabled Fc region, to explore effects on motor outcomes poststroke. METHODS: In this phase IIb double-blind, randomized, placebo-controlled study, @entity1 at 30 centers with @entity385 24 to 72 hours prior and gait deficits were randomized to 2 IV infusions of GSK249320 or placebo. Primary outcome measure was change in gait velocity from baseline to day 90. RESULTS: A total of 134 subjects were randomized between May 2013 and July 2014. The 2 groups were overall well matched at baseline. The study was stopped at the prespecified interim analysis because the treatment difference met the predefined futility criteria cutoff; change in gait velocity to day 90 was 0.55  0.46 (mean  SD) in the GSK249320 group and 0.56  0.50 for placebo. Secondary end points including upper extremity function were concordant. The 2 IV infusions of GSK249320 were well tolerated. No neutralizing antibodies to GSK249320 were detected. CONCLUSIONS: GSK249320, within 72 hours of @entity64 , demonstrated no improvement on gait velocity compared with placebo. Possible reasons include challenges translating findings into @entity1 and no direct evidence that the therapy reached the biological target. The antibody was well tolerated and showed low immunogenicity, findings potentially useful to future studies aiming to use a monoclonal antibody to modify activity in specific biological pathways to improve recovery from @entity64 . CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01808261.

Proof-of-Concept Randomized Trial of the Monoclonal Antibody GSK249320 Versus Placebo in XXXX @entity1 .

@entity1 :: ('9606', 'Species') :: ['humans', 'patients'] @entity64 :: ('MESH:D020521', 'Disease') :: ['stroke'] @entity10838 :: ('4099', 'Gene') :: ['myelin-associated glycoprotein'] @entity385 :: ('MESH:D002544', 'Disease') :: ['ischemic stroke']
@entity64 :: (MESH:D020521,Disease) :: ['Stroke']
