Journal article
Safety and pharmacology of a single intravenous dose of ponezumab in subjects with mild-to-moderate alzheimer disease: A phase I, randomized, placebo-controlled, double-blind, dose-escalation study
JW Landen, Q Zhao, S Cohen, M Borrie, M Woodward, CB Billing, K Bales, C Alvey, F McCush, J Yang, JW Kupiec, MM Bednar
Clinical Neuropharmacology | LIPPINCOTT WILLIAMS & WILKINS | Published : 2013
Abstract
OBJECTIVES: Ponezumab is a humanized antiamyloid beta (Aβ) monoclonal antibody designed to treat Alzheimer disease (AD). METHODS: This randomized, double-blind, single-dose-escalation study evaluated the safety, pharmacokinetics, and pharmacodynamics of 0.1, 0.3, 1, 3, and 10 mg/kg ponezumab (n = 4, 4, 4, 6, and 8, respectively) versus placebo (n = 11) after a 2-hour intravenous infusion in subjects with mild-to-moderate AD. Cerebrospinal fluid (CSF) samples were obtained from the 1-and 10-mg/kg groups at baseline and at day 29. The subjects were followed for 1 year. RESULTS: All subjects completed the trial. Ponezumab was well tolerated with no drug-attributed serious adverse events. The mo..
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Funding Acknowledgements
Jaren W. Landen, Qinying Zhao, Clare B. Billing, Jr, Kelly Bales, Christine Alvey, Fred McCush, Jerry Yang, JamesW. Kupiec, and Martin M. Bednar are Pfizer employees with equity ownership. Michael Borrie and Michael Woodward have received speaker's honoraria and advisory board consultancy fees from Pfizer. Sharon Cohen has no conflicts to declare. This study was sponsored by Pfizer Inc.The authors thank the study sponsor, Pfizer Inc and Susanne Gilbert of ACUMED (New York, NY) for writing and editorial assistance. Likewise, the authors thank all study investigators and the subjects and caregivers who participated in this first inpatient study of ponezumab. The authors also express appreciation to Carol Cronenberger for review of the manuscript, to Kathleen Wood and Kieran Geoghegan for the IP/MS analysis, to Catherine Sattler for review of safety data, to Drs Clifford Jack and Kejal Kantarci for review and scientific interpretation of brain MRI data, and to Denise Reyes and Bret Borowski for assistance with the organization and acquisition sequence setup of the brain MRI data.