Gerald Novak1, Nick Fox2, Shona Clegg2, Casper Nielsen2, Steven Einstein1, Yuan Lu3, Iulia Cristina Tudor4, Keith Gregg5, Jianing Di6, Peter Collins7, Bradley T Wyman8, Eric Yuen5, Michael Grundman9, H Robert Brashear10, Enchi Liu6. 1. Janssen Research and Development, Titusville, NJ, USA. 2. Dementia Research Centre, University College London Institute of Neurology, London, UK. 3. Jazz Pharmaceuticals, Palo Alto, CA, USA. 4. Medivation, Inc., San Francisco, CA, USA. 5. Janssen Alzheimer Immunotherapy, South San Francisco, CA, USA. 6. Janssen Research and Development, San Diego, CA, USA. 7. BioMarin, Novato, CA, USA. 8. Pfizer Inc, Groton, CT, USA. 9. Global R&D Partners, LLC, San Diego, CA, USA. 10. Janssen Research and Development, Fremont, CA, USA.
Abstract
BACKGROUND:Bapineuzumab, an anti-amyloid-β monoclonal antibody, was evaluated in two placebo-controlled trials in APOE*ɛ4 carriers and noncarriers, respectively, with Alzheimer's disease. OBJECTIVES: A volumetric magnetic resonance imaging substudy was performed to determine if bapineuzumab altered brain volume rate of change. METHODS:Bapineuzumab dosages included 0.5 mg/kg in carriers and 0.5 or 1.0 mg/kg in noncarriers, every 13 weeks for 78 weeks. Volumetric outcomes included annualized brain, ventricular, and mean hippocampal boundary shift integrals (BBSI; VBSI; HBSI) up to Week 71. Treatment differences were estimated using mixed models for repeated measures. RESULTS: For BBSI and HBSI, there were no significant treatment-related differences within either study, but, compared to pooled carriers and noncarriers receiving placebo, noncarriers receiving1.0 mg/kg bapineuzumab had greater increases in these measures. Bapineuzumab-treated patients showed significantly greater VBSI rates compared with placebo for 0.5 mg/kg in carriers and 1.0 mg/kg (but not 0.5 mg/kg) in noncarriers. CONCLUSIONS:Bapineuzumab produced an increase in ventricular volume compared with placebo. Etiology for this increase is unclear but may be related to amyloid-β clearance or its consequences.
RCT Entities:
BACKGROUND:Bapineuzumab, an anti-amyloid-β monoclonal antibody, was evaluated in two placebo-controlled trials in APOE*ɛ4 carriers and noncarriers, respectively, with Alzheimer's disease. OBJECTIVES: A volumetric magnetic resonance imaging substudy was performed to determine if bapineuzumab altered brain volume rate of change. METHODS:Bapineuzumab dosages included 0.5 mg/kg in carriers and 0.5 or 1.0 mg/kg in noncarriers, every 13 weeks for 78 weeks. Volumetric outcomes included annualized brain, ventricular, and mean hippocampal boundary shift integrals (BBSI; VBSI; HBSI) up to Week 71. Treatment differences were estimated using mixed models for repeated measures. RESULTS: For BBSI and HBSI, there were no significant treatment-related differences within either study, but, compared to pooled carriers and noncarriers receiving placebo, noncarriers receiving1.0 mg/kg bapineuzumab had greater increases in these measures. Bapineuzumab-treated patients showed significantly greater VBSI rates compared with placebo for 0.5 mg/kg in carriers and 1.0 mg/kg (but not 0.5 mg/kg) in noncarriers. CONCLUSIONS:Bapineuzumab produced an increase in ventricular volume compared with placebo. Etiology for this increase is unclear but may be related to amyloid-β clearance or its consequences.
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