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From the University Department of Geriatric Medicine (A.J. Bayer), University of Wales College of Medicine, Cardiff; Kingshill Clinical Research Unit (R. Bullock), Victoria Hospital, Swindon; The Research Institute for the Care of the Elderly (Dr. Jones), St Martins Hospital, Bath; Thornhill Research Unit (Dr. Wilkinson), Moorgreen Hospital, Southampton; Department of Clinical Pharmacology (Dr. Paterson), Royal Infirmary, Glasgow, UK; Clinical Biostatistics, Wyeth Research (Dr. Jenkins), Collegeville, PA; and Clinical Development (S.B. Millais and Dr. Donoghue), Elan Pharma Limited, Stevenage, UK.
Address correspondence and reprint requests to Dr. A. Bayer, University Department of Geriatric Medicine, Academic Centre, University of Wales College of Medicine, Llandough Hospital, Penarth Road, Cardiff, South Glamorgan, CF64 2XX, UK; e-mail: bayer{at}cf.ac.uk
Background: Aß42-immunization reduces plaque burden and improves cognition in transgenic mouse models of Alzheimer disease (AD). This phase 1 study evaluated the safety, tolerability, and immunogenicity of AN1792 (human aggregated Aß42) in patients with mild to moderate AD.
Methods: Twenty patients were enrolled into each of four dose groups and randomly assigned to receive IM AN1792 (50 or 225 µg) with QS-21 adjuvant (50 or 100 µg) or QS-21 only (control) in a 4:1 active:control ratio on day 0 and at weeks 4, 12, and 24. Patients could receive up to four additional injections of a polysorbate 80 modified formulation at weeks 36, 48, 60, and 72. Safety, tolerability, immunogenicity, and exploratory evidence of efficacy were evaluated.
Results: Treatment-related adverse events were reported in 19 (23.8%) patients, but no relationship was observed between AN1792 dose and incidence. One patient developed meningoencephalitis that was diagnosed after death (not directly related to study treatment) and 219 days after discontinuing from the study. Five deaths occurred during the study follow-up, but none was considered to be directly related to study treatment. During the period of the first four injections, 23.4% of AN1792-treated patients had a positive anti-AN1792 antibody titer (an anti-AN1792 antibody titer of 
1:1,000). This increased to 58.8% after additional injections with the modified formulation. Disability Assessment for Dementia scores showed less decline among active compared with control patients at week 84 (p = 0.002). No treatment differences were observed in three other efficacy measures.
Conclusions: AN1792 + QS-21 elicited a positive antibody response to Aß42 in more than half of this elderly study population.
Received December 3, 2003. Accepted in final form July 20, 2004.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the January 11 issue to find the title link for this article.
A.J. Bayer, R. Bullock, and Drs. Jones, Wilkinson, and Paterson have received grants or honoraria from Elan Pharmaceuticals, Inc. S.B. Millais and Dr. Donoghue are full-time employees of Elan Pharma Limited, in which Dr. Donoghue also holds equity. Dr. Jenkins is a full-time employee of, holds equity in, and has received honoraria from Wyeth Research.
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