title: Bapineuzumab for mild to moderate Alzheimer's disease in two global, randomized, phase 3 trials.
abstract: BACKGROUND
  Our objective was to evaluate the efficacy (clinical and biomarker) and safety of intravenous bapineuzumab in patients with mild to moderate Alzheimer's disease (AD).
  
  
  METHODS
  Two of four phase 3, multicenter, randomized, double-blind, placebo-controlled, 18-month trials were conducted globally: one in apolipoprotein E ε4 carriers and another in noncarriers. Patients received bapineuzumab 0.5 mg/kg (both trials) or 1.0 mg/kg (noncarrier trial) or placebo every 13 weeks. Coprimary endpoints were change from baseline to week 78 on the 11-item Alzheimer's Disease Assessment Scale-Cognitive subscale and the Disability Assessment for Dementia.
  
  
  RESULTS
  A total of 683 and 329 patients completed the current carrier and noncarrier trials, respectively, which were terminated prematurely owing to lack of efficacy in the two other phase 3 trials of bapineuzumab in AD. The current trials showed no significant difference between bapineuzumab and placebo for the coprimary endpoints and no effect of bapineuzumab on amyloid load or cerebrospinal fluid phosphorylated tau. (Both measures were stable over time in the placebo group.) Amyloid-related imaging abnormalities with edema or effusion were confirmed as the most notable adverse event.
  
  
  CONCLUSIONS
  These phase 3 global trials confirmed lack of efficacy of bapineuzumab at tested doses on clinical endpoints in patients with mild to moderate AD. Some differences in the biomarker results were seen compared with the other phase 3 bapineuzumab trials. No unexpected adverse events were observed.
  
  
  BACKGROUND
  Noncarriers (3000) ClinicalTrials.gov identifier NCT00667810 ; registered 24 Apr 2008. Carriers (3001) ClinicalTrials.gov identifier NCT00676143 ; registered 2 May 2008.
authors.affiliation: University Hospitals Leuven, Department of Neurosciences, Alzheimer Research Centre KU Leuven, Herestraat 49, 3000, Leuven, Belgium. rik.vandenberghe@uzleuven.be.
authors.forename: Rik
authors.initials: R
authors.lastname: Vandenberghe
authors.affiliation: Turku PET Centre and Division of Clinical Neurosciences, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland.
authors.forename: Juha O
authors.initials: JO
authors.lastname: Rinne
authors.affiliation: Fundació ACE, Barcelona Alzheimer Treatment and Research Center, Gran via de Carles III, 85 Bis, 08028, Barcelona, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Boada
authors.affiliation: Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Sadao
authors.initials: S
authors.lastname: Katayama
authors.affiliation: Alzheimercentrum VUmc, Neurology, VU University Medical Center, PO Box 7057, 1007, MB, Amsterdam, Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: CHU Toulouse, Gérontopôle, 170 Avenue de Casselardit, TSA 40031, 31059, Toulouse, Cedex 9, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.affiliation: Palm Beach Neurological Center, 3365 Burns Road, Suite 203, Palm Beach Gardens, FL, 33410, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Tuchman
authors.affiliation: Department of Neurology, University Hospital Mannheim, University Medical Centre Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Gass
authors.affiliation: Center for Stroke Research Berlin (CSB), Charité Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany.
authors.forename: Jochen B
authors.initials: JB
authors.lastname: Fiebach
authors.affiliation: IXICO Ltd., The London Bioscience Innovation Centre, 4th Floor, Griffin Court, 15 Long Lane, London, EC1A 9PN, UK.
authors.forename: Derek
authors.initials: D
authors.lastname: Hill
authors.affiliation: Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
authors.forename: Kasia
authors.initials: K
authors.lastname: Lobello
authors.affiliation: Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
authors.forename: David
authors.initials: D
authors.lastname: Li
authors.affiliation: Pfizer Inc., 235 East 42nd Street, New York, NY, 10017, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: McRae
authors.affiliation: Pfizer Global Research and Development (PGRD), 23-25 avenue Du Docteur Lannelongue, Paris, Île-De-France, 75014, France.
authors.forename: Prisca
authors.initials: P
authors.lastname: Lucas
authors.affiliation: Pfizer Ltd., Walton Oaks, Dorking Road, Tadworth, Surrey, KT20 7NS, UK.
authors.forename: Iona
authors.initials: I
authors.lastname: Evans
authors.affiliation: Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Booth
authors.affiliation: Pfizer Global Research and Development (PGRD), 23-25 avenue Du Docteur Lannelongue, Paris, Île-De-France, 75014, France.
authors.forename: Gerald
authors.initials: G
authors.lastname: Luscan
authors.affiliation: Pfizer Inc., 7 Kings Highway, Groton, CT, 06340, USA.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Wyman
authors.affiliation: Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hua
authors.affiliation: Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
authors.forename: Lingfeng
authors.initials: L
authors.lastname: Yang
authors.affiliation: Janssen Alzheimer Immunotherapy Research & Development, LLC, 700 Gateway Boulevard, South San Francisco, CA, 94080, USA.
authors.forename: H Robert
authors.initials: HR
authors.lastname: Brashear
authors.affiliation: Pfizer Inc., 500 Arcola Road, Collegeville, PA, 19426, USA.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Black
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D012720:Severity of Illness Index; D016896:Treatment Outcome; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D061067:Antibodies, Monoclonal, Humanized; D053327:Apolipoprotein E4; D015415:Biomarkers; C054369:MAPT protein, human; D016875:tau Proteins; C545458:bapineuzumab
keywords: ARIA-E; Alzheimer’s disease; Amyloid β; Bapineuzumab; Clinical trial; Immunotherapy; Vasogenic edema