title: A phase III study evaluating the efficacy and safety of MBP8298 in secondary progressive MS.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of MBP8298 in subjects with secondary progressive multiple sclerosis (SPMS) who express human leukocyte antigen (HLA) haplotype DR2 or DR4 (DR2(+) or DR4(+)).
  
  
  METHODS
  This multicenter randomized 2-year, double-blind, placebo-controlled study included 612 subjects with a diagnosis of SPMS and an Expanded Disability Status Scale (EDSS) score of 3.5-6.5, stratified according to baseline EDSS score (3.5-5.0, or 5.5-6.5) and HLA haplotype (DR2(+) or DR4(+), or DR2(-)/DR4(-)). Upon entry of 100 DR2(-)/DR4(-) subjects, further study enrollment was limited to DR2(+) or DR4(+) subjects. Subjects were randomly assigned to either 500 mg MBP8298 or placebo, given by IV injection once every 6 months for 2 years. The primary outcome measure was time to progression by ≥1.0 EDSS point (or 0.5 point if baseline EDSS was 5.5 or higher), confirmed 6 months later. Secondary outcomes included mean change in EDSS, mean change in Multiple Sclerosis Functional Composite, MRI changes, annualized relapse rate, and quality of life.
  
  
  RESULTS
  There were no significant differences between treatment groups in either the primary or secondary endpoints. MBP8298 was well tolerated in all treated subjects with no safety issues identified.
  
  
  CONCLUSIONS
  In the population studied, treatment with MBP8298 did not provide a clinical benefit compared to placebo.
  
  
  METHODS
  This study provides Class 1 evidence that MBP8298 is not effective in patients with SPMS who are HLA DR2(+) or DR4(+).
authors.affiliation: University of Ottawa, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada. mfreedman@toh.on.ca
authors.forename: M S
authors.initials: MS
authors.lastname: Freedman
authors.forename: A
authors.initials: A
authors.lastname: Bar-Or
authors.forename: J
authors.initials: J
authors.lastname: Oger
authors.forename: A
authors.initials: A
authors.lastname: Traboulsee
authors.forename: D
authors.initials: D
authors.lastname: Patry
authors.forename: C
authors.initials: C
authors.lastname: Young
authors.forename: T
authors.initials: T
authors.lastname: Olsson
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.forename: H-P
authors.initials: HP
authors.lastname: Hartung
authors.forename: M
authors.initials: M
authors.lastname: Krantz
authors.forename: L
authors.initials: L
authors.lastname: Ferenczi
authors.forename: T
authors.initials: T
authors.lastname: Verco
mesh_terms: D000328:Adult; D000368:Aged; D004185:Disability Evaluation; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D004676:Myelin Basic Protein / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000627:therapeutic use*; D011788:Quality of Life; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004676:Myelin Basic Protein; D010446:Peptide Fragments; C526227:MBP-8298