1. Ponezumab in mild-to-moderate Alzheimer's disease: Randomized phase II PET-PIB study
- Author
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Jaren W. Landen, Niels Andreasen, Carol Cronenberger, Henrik Östlund, Martin M. Bednar, Anne Börjesson-Hanson, Pamela F. Schwartz, Catherine Sattler, and Brendon Binneman
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Amyloid ,Neurology ,Pharmacology ,Placebo ,Loading dose ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,Ponezumab ,Pharmacokinetics ,Anti-drug antibodies ,Medicine ,Antibody ,business.industry ,PIB ,Featured Article ,Alzheimer's disease ,Tolerability ,Psychiatry and Mental health ,030104 developmental biology ,Pharmacodynamics ,Neurology (clinical) ,Safety ,business ,030217 neurology & neurosurgery - Abstract
Introduction The safety, pharmacokinetics, and effect on peripheral and central amyloid β (Aβ) of multiple doses of ponezumab, an anti-Aβ monoclonal antibody, were characterized in subjects with mild-to-moderate Alzheimer's disease treated for 1 year. Methods Subjects were aged ≥50 years with Mini–Mental State Examination scores 16 to 26. Cohort Q was randomized to ponezumab 10 mg/kg ( n = 12) or placebo ( n = 6) quarterly. Cohort M was randomized to a loading dose of ponezumab 10 mg/kg or placebo, followed by monthly ponezumab 7.5 mg/kg ( n = 12) or placebo ( n = 6), respectively. Results Ponezumab was generally well tolerated. Plasma concentrations increased dose dependently, but cerebrospinal fluid (CSF) penetration was low. Plasma Aβ increased dose dependently with ponezumab, but CSF biomarkers, brain amyloid burden, cognition, and function were not affected. Conclusions Both ponezumab dosing schedules were generally safe and well tolerated but did not alter CSF biomarkers, brain amyloid burden, or clinical outcomes.
- Published
- 2017