Title | Two Phase 2 Multiple Ascending-Dose Studies of Vanutide Cridificar (ACC-001) and QS-21 Adjuvant in Mild-to-Moderate Alzheimer's Disease. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Pasquier, F, Sadowsky, C, Holstein, A, Leterme, GLe Prince, Peng, Y, Jackson, N, Fox, NC, Ketter, N, Liu, E, J Ryan, M |
Corporate Authors | ACC-001 (QS-21) Study Team |
Journal | J Alzheimers Dis |
Volume | 51 |
Issue | 4 |
Pagination | 1131-43 |
Date Published | 2016 |
ISSN | 1875-8908 |
Keywords | Adjuvants, Immunologic, Aged, Alzheimer Disease, Amyloid beta-Peptides, Antipsychotic Agents, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Interferon-gamma, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Peptide Fragments, Recombinant Fusion Proteins, Saponins, Single-Blind Method, Treatment Outcome |
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. |
DOI | 10.3233/JAD-150376 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 26967206 |