title: Long-Term Extensions of Randomized Vaccination Trials of ACC-001 and QS-21 in Mild to Moderate Alzheimer's Disease.
abstract: Long-term safety and tolerability of ACC-001 (vanutide cridificar), an antiamyloid- beta therapeutic vaccine, was evaluated in subjects with mild to moderate Alzheimer's disease.
  
  
  
  Phase 2a extension studies of randomized parent trials were conducted in the United States, European Union, and Japan.
  
  
  
  Four immunizations of ACC-001 were administered at the same 3 dose levels (3, 10, and 30 μg) to subjects randomized in the parent studies; ACC-001 was administered with QS-21 adjuvant. Safety, tolerability, and immunogenicity were assessed during active treatment and 6-month follow-up.
  
  
  
  ACC-001 + QS-21 was well tolerated in the United States (N=110) and European Union (N=50), and Japan (N=53) extension studies; safety profile was similar to that observed in the parent studies, and no new safety signals were identified. Overall, injection site reactions were the most common adverse event in these studies. Anti-amyloid antibody titers were elicited in all groups, with the highest titers observed in subjects who received ACC-001 + QS-21 in both the parent and extension studies.
  
  
  
  Long-term exposure to ACC-001 + QS-21 was well tolerated in subjects with Alzheimer's disease, suggesting that side effects do not pose a principal limitation for anti-amyloid active immunotherapy. The highest anti-amyloid-beta IgG titers are elicited during long-term therapy with ACC-001 + QS-21 compared with other regimens.
authors.affiliation: Clinic for Geriatric Psychiatry, Center for Psychiatry Emmendingen, Neubronnstraße 25, D-79312 Emmendingen. Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hull
authors.affiliation: Premiere Research Institute, Palm Beach Neurology, Nova SE University, 4631 North Congress Ave., Suite 200, West Palm Beach, FL 33407, United States.
authors.forename: Carl
authors.initials: C
authors.lastname: Sadowsky
authors.affiliation: Department of Psychiatry & Behavioral Science, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Heii
authors.initials: H
authors.lastname: Arai
authors.affiliation: Pfizer Global Research and Development, 23-25 avenue du Docteur Lannelongue, 75668 Paris cedex 14. France.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Le Prince Leterme
authors.affiliation: Pfizer Inc., 500 Arcola Road, Collegeville, PA 19426, United States.
authors.forename: Ann
authors.initials: A
authors.lastname: Holstein
authors.affiliation: Pfizer Inc., 500 Arcola Road, Collegeville, PA 19426, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Booth
authors.affiliation: Pfizer Inc., 500 Arcola Road, Collegeville, PA 19426, United States.
authors.forename: Yahong
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Pfizer Japan Inc., 3-22-7 Yoyogi, Shibuya-ku, Tokyo 151- 8589, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Yoshiyama
authors.affiliation: Pfizer Japan Inc., 3-22-7 Yoyogi, Shibuya-ku, Tokyo 151- 8589, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Janssen Research and Development, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors.forename: Nzeera
authors.initials: N
authors.lastname: Ketter
authors.affiliation: Janssen Research and Development, 3210 Merryfield Row, San Diego, CA 92121, United States.
authors.forename: Enchi
authors.initials: E
authors.lastname: Liu
authors.affiliation: Pfizer Inc., 500 Arcola Road, Collegeville, PA 19426, United States.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Ryan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000276:immunology* / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005060:Europe; D005260:Female; D006801:Humans; D007391:International Cooperation; D007564:Japan; D008137:Longitudinal Studies; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D012503:Saponins / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States; D014611:Vaccination / Q000379:methods*
chemical_list: D016229:Amyloid beta-Peptides; D011993:Recombinant Fusion Proteins; D012503:Saponins; C078785:saponin QA-21V1; C000603458:vanutide cridificar
keywords: Alzheimer’s disease; amyloid plaques; amyloid-beta; antibody; immunotherapy; vaccine