Ponezumab in mild-to-moderate Alzheimer's disease : Randomized phase II PET-PIB study
(2017) In Alzheimer's and Dementia: Translational Research and Clinical Interventions 3(3). p.393-401- 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... (More)
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.
(Less)
- author
- Landen, Jaren W. ; Andreasen, Niels ; Cronenberger, Carol L. ; Schwartz, Pamela F. ; Börjesson-Hanson, Anne ; Östlund, Henrik LU ; Sattler, Catherine A. ; Binneman, Brendon and Bednar, Martin M.
- organization
- publishing date
- 2017-09-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer's disease, Amyloid, Anti-drug antibodies, Antibody, Pharmacodynamics, Pharmacokinetics, PIB, Ponezumab, Safety, Tolerability
- in
- Alzheimer's and Dementia: Translational Research and Clinical Interventions
- volume
- 3
- issue
- 3
- pages
- 9 pages
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:85022009680
- pmid:29067345
- DOI
- 10.1016/j.trci.2017.05.003
- language
- English
- LU publication?
- yes
- id
- 9e7fa0b5-9011-4c6e-90bb-6f648eebfb46
- date added to LUP
- 2017-07-31 10:30:44
- date last changed
- 2024-12-09 15:55:46
@article{9e7fa0b5-9011-4c6e-90bb-6f648eebfb46, abstract = {{<p>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.</p>}}, author = {{Landen, Jaren W. and Andreasen, Niels and Cronenberger, Carol L. and Schwartz, Pamela F. and Börjesson-Hanson, Anne and Östlund, Henrik and Sattler, Catherine A. and Binneman, Brendon and Bednar, Martin M.}}, keywords = {{Alzheimer's disease; Amyloid; Anti-drug antibodies; Antibody; Pharmacodynamics; Pharmacokinetics; PIB; Ponezumab; Safety; Tolerability}}, language = {{eng}}, month = {{09}}, number = {{3}}, pages = {{393--401}}, publisher = {{John Wiley & Sons Inc.}}, series = {{Alzheimer's and Dementia: Translational Research and Clinical Interventions}}, title = {{Ponezumab in mild-to-moderate Alzheimer's disease : Randomized phase II PET-PIB study}}, url = {{http://dx.doi.org/10.1016/j.trci.2017.05.003}}, doi = {{10.1016/j.trci.2017.05.003}}, volume = {{3}}, year = {{2017}}, }