Vanutide Cridificar (ACC-001) and QS-21 Adjuvant in Individuals with Early Alzheimer's Disease: Amyloid Imaging Positron Emission Tomography and Safety Results from a Phase 2 Study.

Autor:	van Dyck CH; Christopher H. van Dyck, MD, Professor of Psychiatry, Neurology, and Neurobiology, Director, Alzheimers Disease Research Unit, Yale University School of Medicine, One Church Street, Suite 600, New Haven, CT 06510 USA, Tel: 1-203-764-8100, Fax: 1-203-764-8111, E-mail: christopher.vandyck@yale.edu., Sadowsky C, Le Prince Leterme G, Booth K, Peng Y, Marek K, Ketter N, Liu E, Wyman BT, Jackson N, Slomkowski M, Ryan JM
Jazyk:	angličtina
Zdroj:	The journal of prevention of Alzheimer's disease [J Prev Alzheimers Dis] 2016; Vol. 3 (2), pp. 75-84.
DOI:	10.14283/jpad.2016.91
Abstrakt:	Background: ACC-001 is an investigational therapeutic vaccine designed to elicit antibodies against the N-terminal peptide 1-7 of the amyloid-beta peptide, believed to be important in the pathogenesis of Alzheimer's disease. Objectives: To evaluate safety, immunogenicity, impact on brain amyloid, and other exploratory endpoints in participants receiving ACC-001. Design: Randomized, phase 2, interventional study. Trial Registration: Clinicaltrials.gov ID NCT01227564. Participants: Individuals with early Alzheimer's disease (Mini-Mental State Examination scores ≥25, a global Clinical Dementia Rating of 0.5, and evidence of elevated baseline brain amyloid burden). Intervention: Participants were randomized to ACC-001 3 µg or 10 µg with QS-21 adjuvant (50 µg), or placebo. Measurements: The primary endpoint was change in brain amyloid burden by 18F-florbetapir positron emission tomography in composite cortical standard uptake value ratio. Results: A total of 63 participants were randomized and 51 completed the study. At week 104, no significant differences were observed in 18F-florbetapir positron emission tomography composite cortical standard uptake value ratio between either ACC-001 dose compared with placebo. In both ACC-001 + QS-21 treatment groups, following the initial immunization, the anti-amyloid-beta geometric mean titers increased after each subsequent vaccination and then declined, with less apparent decline after the later compared with earlier immunizations. The majority of treatment-emergent adverse events in the ACC-001 + QS-21 groups were injection site reactions, which occurred at a greater rate in active treatment groups than in the placebo group. No amyloid-related imaging abnormalities of edema or effusion were reported. Conclusion: No statistically significant differences were observed between groups in the change from baseline brain amyloid burden despite apparently robust systemically measured anti-amyloid-beta antibody response at both dose levels. Insufficient antibody titers, poor quality immune response, short duration of treatment, or small sample size may have resulted in these findings. The safety and tolerability profile was acceptable. Competing Interests: C.H. van Dyck reports grants from Pfizer Inc during the conduct of the study. He also reports grants from Baxter Pharmaceuticals, Biogen Idec, Eisai, Inc., Eli Lilly and Company, Forum Pharmaceuticals, Genentech, Inc., Merck and Co. Inc., Pfizer Inc, TauRx, Toyama Chemical Co., Ltd., and Wyeth Research; grants and personal fees from Bristol-Myers Squibb Company, Janssen, and Roche Pharmaceuticals; and personal fees from AbbVie, outside the submitted work. C. Sadowsky reports financial relationships for advisory boards with Alzheon Pharmaceutical and Cognoptix Pharmaceutical and for speaker bureaus with Novartis Pharmaceuticals Corporation, Lilly, Pam Lab, and Forest. G. Le Prince Leterme is an employee of Pfizer Inc. K. Booth is an employee of Pfizer Inc, has stock options, and owns company stock. Y. Peng is an employee of Pfizer Inc. K. Marek reports personal fees from Molecular Neuroimaging, and owns company stock. He is a consultant for Bristol-Myers Squibb Company, GE Healthcare, Lilly, Lysosomal Therapeutic, Inc., Merck and Co. Inc., Pfizer Inc, Piramal, Prothena, Oxford Biomedica, and Roche Pharmaceuticals. N. Ketter is an employee of Janssen R and D. E. Liu was an employee of Janssen R and D at the time the study was conducted and manuscript developed. B.T. Wyman was an employee of Pfizer Inc at the time the study was conducted and owns company stock. N. Jackson was an employee of Pfizer Inc at the time the study was conducted. M. Slomkowski was an employee of Pfizer Inc at the time the study was conducted. J.M. Ryan was an employee of Pfizer Inc at the time the study was conducted.
Databáze:	MEDLINE
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