title: Two Phase 2 Multiple Ascending-Dose Studies of Vanutide Cridificar (ACC-001) and QS-21 Adjuvant in Mild-to-Moderate Alzheimer's Disease.
abstract: Vanutide cridificar (ACC-001), an immunotherapeutic vaccine, is a potentially disease-modifying therapy that aims to reduce brain amyloid-β (Aβ) plaques in patients with Alzheimer's disease (AD). ACC-001 was evaluated in two phase 2a, multicenter, randomized, third party-unblinded, placebo-controlled, multiple ascending-dose studies of ACC-001 (3μg, 10μg, 30μg) with and without QS-21 adjuvant that enrolled patients with mild-to-moderate AD (n = 245). Patients were treated with up to five doses of study vaccine or placebo and followed for safety and tolerability (primary objective) and anti-Aβ IgG immunogenicity (secondary objective) up to 12 months after the last vaccination. Exploratory assessments included cognitive/functional measures, brain magnetic resonance imaging (MRI) volumetry, and pharmacodynamic markers in plasma and cerebrospinal fluid (CSF). The most frequent treatment-emergent adverse events (≥10%) were local injection reactions and headache. Amyloid-related imaging abnormalities with vasogenic edema occurred in two (0.8%) patients (ACC-001 30μg + QS-21; ACC-001 10μg). ACC-001 + QS-21 elicited consistently higher peak and sustained anti-Aβ IgG titers compared with ACC-001 alone. Plasma Aβx-40 was significantly higher in all ACC-001 + QS-21 groups versus placebo (weeks 16-56), with no evidence of dose response. Exploratory cognitive evaluations, volumetric brain MRI, and CSF biomarkers did not show differences or trends between treatment groups and placebo. ACC-001 with or without QS-21 adjuvant has an acceptable safety profile in patients with mild-to-moderate AD.
authors.affiliation: Inserm U1171, Memory clinic of CHU and University of Lille, Lille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Pasquier
authors.affiliation: Premiere Research Institute, Palm Beach Neurology, Nova SE University, West Palm Beach, FL, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Sadowsky
authors.affiliation: Pfizer Vaccine R&D, Collegeville, PA, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Holstein
authors.affiliation: Pfizer Global Research and Development, Paris cedex 14 - France.
authors.forename: Ghislaine Le Prince
authors.initials: Gle P
authors.lastname: Leterme
authors.affiliation: Pfizer Vaccine R&D, Collegeville, PA, USA.
authors.forename: Yahong
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Pfizer Vaccine R&D, Collegeville, PA, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Jackson
authors.affiliation: Dementia Research Centre, Department of Neurodegeneration, UCL Institute of Neurology, London, UK.
authors.forename: Nick C
authors.initials: NC
authors.lastname: Fox
authors.affiliation: Janssen Research and Development, San Diego, CA, USA.
authors.forename: Nzeera
authors.initials: N
authors.lastname: Ketter
authors.affiliation: Janssen Research and Development, San Diego, CA, USA.
authors.forename: Enchi
authors.initials: E
authors.lastname: Liu
authors.affiliation: Pfizer Vaccine R&D, Collegeville, PA, USA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Ryan
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000097:blood; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000097:blood; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D012503:Saponins / Q000627:therapeutic use*; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D016229:Amyloid beta-Peptides; D014150:Antipsychotic Agents; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D012503:Saponins; C075222:amyloid beta-protein (1-42); C078785:saponin QA-21V1; D007371:Interferon-gamma; C000603458:vanutide cridificar
keywords: Active immunization; Alzheimer’s disease; amyloid plaques; amyloid-β peptides; amyloid-β protein; clinical trial; immunotherapy