Abstract
Introduction Multiple intravenous doses of ponezumab, an anti-amyloid antibody, were evaluated in subjects with mild-to-moderate Alzheimer's disease (AD). Methods In part A, 77 subjects were randomized to ponezumab 0.1, 0.5, or 1 mg/kg (75 treated) and 26 to placebo (24 treated). In part B, 63 subjects were randomized and treated with ponezumab 3 or 8.5 mg/kg and 32 with placebo. Subjects received 10 infusions over 18 months and were followed for 6 months thereafter. Results Ponezumab was generally safe and well tolerated. Most common adverse events were fall (16.7% ponezumab, 21.4% placebo), headache (13.8%, 21.4%), and cerebral microhemorrhage (13.8%, 19.6%). Plasma ponezumab increased dose-dependently with limited accumulation. Cerebrospinal fluid penetration was low. Plasma Aβ1–x and Aβ1–40 showed robust increases, but cerebrospinal fluid biomarkers showed no dose response. Ponezumab had no effects on cognitive/functional outcomes or brain volume. Conclusions Multiple-dose ponezumab was generally safe, but not efficacious, in mild-to-moderate AD.
Original language | English (US) |
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Pages (from-to) | 339-347 |
Number of pages | 9 |
Journal | Alzheimer's and Dementia: Translational Research and Clinical Interventions |
Volume | 3 |
Issue number | 3 |
DOIs | |
State | Published - Sep 2017 |
Keywords
- Alzheimer's disease
- Amyloid β
- Biomarkers
- Cerebrospinal fluid
- Immunotherapy
- Monoclonal antibody
- Pharmacodynamics
- Pharmacokinetics
- Phase-II study
- Ponezumab
ASJC Scopus subject areas
- Clinical Neurology
- Psychiatry and Mental health