%0 Journal Article %J J Alzheimers Dis %D 2016 %T Two Phase 2 Multiple Ascending-Dose Studies of Vanutide Cridificar (ACC-001) and QS-21 Adjuvant in Mild-to-Moderate Alzheimer's Disease. %A Pasquier, Florence %A Sadowsky, Carl %A Holstein, Ann %A Leterme, Ghislaine Le Prince %A Peng, Yahong %A Jackson, Nicholas %A Fox, Nick C %A Ketter, Nzeera %A Liu, Enchi %A Ryan, J Michael %K Adjuvants, Immunologic %K Aged %K Alzheimer Disease %K Amyloid beta-Peptides %K Antipsychotic Agents %K Dose-Response Relationship, Drug %K Female %K Follow-Up Studies %K Humans %K Interferon-gamma %K Magnetic Resonance Imaging %K Male %K Middle Aged %K Neuropsychological Tests %K Peptide Fragments %K Recombinant Fusion Proteins %K Saponins %K Single-Blind Method %K Treatment Outcome %X

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.

%B J Alzheimers Dis %V 51 %P 1131-43 %8 2016 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/26967206?dopt=Abstract %R 10.3233/JAD-150376