title: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Safety, Pharmacokinetics, and Biomarker Results of Subcutaneous Bapineuzumab in Patients with mild to moderate Alzheimer's disease.
abstract: Bapineuzumab, a humanized monoclonal antibody, targets amyloid-β (Aβ1-40/1 -42) that is believed to play a key role in the pathogenesis of Alzheimer disease (AD).
  
  
  
  To assess the effects of monthly subcutaneous (SC) bapineuzumab versus placebo on cerebral amyloid signal in amyloid-positive patients with mild to moderate AD. The incidence of amyloid-related imaging abnormalities-edema/effusion (ARIA-E), pharmacokinetics, pharmacodynamics, immunogenicity, and other safety aspects of bapineuzumab were also evaluated.
  
  
  
  In this multicenter, double-blind study, 146 patients were randomized (1 : 1:1 : 1) to SC bapineuzumab 2, 7, or 20 mg/month or placebo. Lack of efficacy of intravenous (IV) bapineuzumab in Phase III studies led to truncation of the treatment duration from 24 months to 12 months. Primary endpoint: change from baseline to month 12 in brain amyloid signal as measured by standardized uptake value ratio (SUVR) using florbetapir positron emission tomography (PET).
  
  
  
  Florbetapir PET SUVR decreased significantly (p = 0.038) from baseline to month 12 for the bapineuzumab 7 mg/month group only; reductions versus placebo were not significant for any dosage. One patient each in bapineuzumab 2 mg/month and 20 mg/month groups had ARIA-E. The percentages of patients with treatment-emergent adverse events were similar in placebo (77.8%) and bapineuzumab 2 mg/month (78.4%) group, but higher in 7 mg/month (94.4%) and 20 mg/month (89.2%) groups.
  
  
  
  Bapineuzumab SC once-monthly did not demonstrate significant treatment difference over placebo on cerebral amyloid signal at one year but was well-tolerated. There was less ARIA-E than had been expected based on prior experience with comparable exposure on IV bapineuzumab.
authors: Brain Matters Research, Delray Beach, FL, USA.
authors: Mark
authors: M
authors: Brody
authors: Janssen Research & Development, San Diego, CA, USA.
authors: Enchi
authors: E
authors: Liu
authors: Janssen Research & Development, San Diego, CA, USA.
authors: Jianing
authors: J
authors: Di
authors: Janssen Research & Development, Spring House, PA, USA.
authors: Ming
authors: M
authors: Lu
authors: Janssen Alzheimer Immunotherapy, South San Francisco, CA, USA.
authors: Richard A
authors: RA
authors: Margolin
authors: Pfizer Inc., Collegeville, PA, USA.
authors: John L
authors: JL
authors: Werth
authors: Pfizer Inc., Collegeville, PA, USA.
authors: Kevin
authors: K
authors: Booth
authors: Janssen Research & Development, Fremont, CA, USA.
authors: Anna
authors: A
authors: Shadman
authors: Janssen Research & Development, Fremont, CA, USA.
authors: H Robert
authors: HR
authors: Brashear
authors: Janssen Pharmaceutical Research and Development, Titusville, NJ, USA.
authors: Gerald
authors: G
authors: Novak
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000097:blood; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D049268:Positron-Emission Tomography / Q000639:trends
chemical_list: D016229:Amyloid beta-Peptides; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C545458:bapineuzumab
keywords: Alzheimer’s disease; amyloid burden; bapineuzumab; biomarker; pharmacokinetics