Two Phase 2 Multiple Ascending-Dose Studies of Vanutide Cridificar (ACC-001) and QS-21 Adjuvant in Mild-to-Moderate Alzheimer's Disease

J Alzheimers Dis. 2016;51(4):1131-43. doi: 10.3233/JAD-150376.


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.

Trial registration: NCT00479557 NCT00498602.

Keywords: Active immunization; Alzheimer’s disease; amyloid plaques; amyloid-β peptides; amyloid-β protein; clinical trial; immunotherapy.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Aged
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / drug therapy*
  • Amyloid beta-Peptides / blood
  • Antipsychotic Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Interferon-gamma / blood
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Peptide Fragments / blood
  • Recombinant Fusion Proteins / therapeutic use*
  • Saponins / therapeutic use*
  • Single-Blind Method
  • Treatment Outcome


  • Adjuvants, Immunologic
  • Amyloid beta-Peptides
  • Antipsychotic Agents
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Saponins
  • amyloid beta-protein (1-42)
  • saponin QA-21V1
  • Interferon-gamma
  • vanutide cridificar

Associated data

  • EudraCT/2006-002061-39