title: Proof-of-Concept Randomized Trial of the Monoclonal Antibody GSK249320 Versus Placebo in Stroke Patients.
abstract: One class of poststroke restorative therapy focuses on promoting axon outgrowth by blocking myelin-based inhibitory proteins such as myelin-associated glycoprotein. The purpose of the current study was to extend preclinical and clinical findings of GSK249320, a humanized monoclonal antibody to myelin-associated glycoprotein with disabled Fc region, to explore effects on motor outcomes poststroke.
  
  
  
  In this phase IIb double-blind, randomized, placebo-controlled study, patients at 30 centers with ischemic stroke 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.
  
  
  
  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.
  
  
  
  GSK249320, within 72 hours of stroke, demonstrated no improvement on gait velocity compared with placebo. Possible reasons include challenges translating findings into humans 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 stroke.
  
  
  
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01808261.
authors.affiliation: From the Department of Neurology, University of California, Irvine (S.C.C.); GlaxoSmithKline Research and Development, Research Triangle Park, NC (L.A.E., C.K.R., T.R.T.); PAREXEL International, Durham, NC (C.K.R.); GlaxoSmithKline Research and Development, Stockley Park, United Kingdom (M.S.); and Medpace Inc, Cincinnati, OH (T.R.T.). scramer@uci.edu.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Cramer
authors.affiliation: From the Department of Neurology, University of California, Irvine (S.C.C.); GlaxoSmithKline Research and Development, Research Triangle Park, NC (L.A.E., C.K.R., T.R.T.); PAREXEL International, Durham, NC (C.K.R.); GlaxoSmithKline Research and Development, Stockley Park, United Kingdom (M.S.); and Medpace Inc, Cincinnati, OH (T.R.T.).
authors.forename: Lori A
authors.initials: LA
authors.lastname: Enney
authors.affiliation: From the Department of Neurology, University of California, Irvine (S.C.C.); GlaxoSmithKline Research and Development, Research Triangle Park, NC (L.A.E., C.K.R., T.R.T.); PAREXEL International, Durham, NC (C.K.R.); GlaxoSmithKline Research and Development, Stockley Park, United Kingdom (M.S.); and Medpace Inc, Cincinnati, OH (T.R.T.).
authors.forename: Colleen K
authors.initials: CK
authors.lastname: Russell
authors.affiliation: From the Department of Neurology, University of California, Irvine (S.C.C.); GlaxoSmithKline Research and Development, Research Triangle Park, NC (L.A.E., C.K.R., T.R.T.); PAREXEL International, Durham, NC (C.K.R.); GlaxoSmithKline Research and Development, Stockley Park, United Kingdom (M.S.); and Medpace Inc, Cincinnati, OH (T.R.T.).
authors.forename: Monica
authors.initials: M
authors.lastname: Simeoni
authors.affiliation: From the Department of Neurology, University of California, Irvine (S.C.C.); GlaxoSmithKline Research and Development, Research Triangle Park, NC (L.A.E., C.K.R., T.R.T.); PAREXEL International, Durham, NC (C.K.R.); GlaxoSmithKline Research and Development, Stockley Park, United Kingdom (M.S.); and Medpace Inc, Cincinnati, OH (T.R.T.).
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Thompson
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D018992:Myelin-Associated Glycoprotein / Q000037:antagonists & inhibitors*; D015990:Placebo Effect; D020521:Stroke / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018992:Myelin-Associated Glycoprotein; C581856:refanezumab
keywords: axon; brain; clinical trial; gait; stroke