title: Safety and tolerability of BAN2401--a clinical study in Alzheimer's disease with a protofibril selective Aβ antibody.
abstract: BACKGROUND
  Several monoclonal antibodies for the treatment of Alzheimer's disease (AD) have been in development over the last decade. BAN2401 is a monoclonal antibody that selectively binds soluble amyloid β (Aβ) protofibrils.
  
  
  METHODS
  Here we describe the first clinical study with BAN2401. Safety and tolerability were investigated in mild to moderate AD. A study design was used with staggered parallel single and multiple ascending doses, from 0.1 mg/kg as a single dose to 10 mg/kg biweekly for four months. The presence of amyloid related imaging abnormalities (ARIA, E for edema, H for hemorrhage) was assessed with magnetic resonance imaging (MRI). Cerebrospinal fluid (CSF) and plasma samples were analyzed to investigate pharmacokinetics (PK) and effects on biomarkers.
  
  
  RESULTS
  The incidence of ARIA-E/H on MRI was comparable to that of placebo. BAN2401 exposure was approximately dose proportional, with a serum terminal elimination half-life of ~7 days. Only a slight increase of plasma Aβ(1-40) was observed but there were no measurable effects of BAN2401 on CSF biomarkers. On the basis of these findings Phase 2b efficacy study has been initiated in early AD.
  
  
  CONCLUSIONS
  BAN2401 was well-tolerated across all doses. The PK profile has guided us for selecting dose and dose regimens in the ongoing phase 2b study. There was no clear guidance for an effective dose based on biomarkers.
  
  
  BACKGROUND
  NCT01230853 ClinicalTrials.gov Registered October 27, 2010.
authors.affiliation: Eisai, Inc., 100 Tice Blvd, Woodcliff Lake, NJ, 07677, USA.
authors.forename: Veronika
authors.initials: V
authors.lastname: Logovinsky
authors.affiliation: Eisai, Inc., 100 Tice Blvd, Woodcliff Lake, NJ, 07677, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Satlin
authors.affiliation: Eisai, Inc., 100 Tice Blvd, Woodcliff Lake, NJ, 07677, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Lai
authors.affiliation: Eisai, Inc., 100 Tice Blvd, Woodcliff Lake, NJ, 07677, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Swanson
authors.affiliation: Eisai, Inc., 100 Tice Blvd, Woodcliff Lake, NJ, 07677, USA.
authors.forename: June
authors.initials: J
authors.lastname: Kaplow
authors.affiliation: BioArctic Neuroscience AB, Warfvinges väg 35, 112 51, Stockholm, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Osswald
authors.affiliation: BioArctic Neuroscience AB, Warfvinges väg 35, 112 51, Stockholm, Sweden.|Department of Public Health/Geriatrics, Uppsala University, Dag Hammarskiölds väg 14 B, 751 85, Uppsala, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Basun
authors.affiliation: BioArctic Neuroscience AB, Warfvinges väg 35, 112 51, Stockholm, Sweden. Lars.Lannfelt@pubcare.uu.se.|Department of Public Health/Geriatrics, Uppsala University, Dag Hammarskiölds väg 14 B, 751 85, Uppsala, Sweden. Lars.Lannfelt@pubcare.uu.se.
authors.forename: Lars
authors.initials: L
authors.lastname: Lannfelt
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000097:blood / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000097:blood
chemical_list: D016229:Amyloid beta-Peptides; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D010446:Peptide Fragments; C497285:amyloid beta-protein (1-41); C000612089:lecanemab
keywords: ARIA; Alzheimer's disease; Amyloid-β; Aβ; BAN2401; Clinical trial; Immunotherapy; Protofibril; mAb158