Safety and Immunogenicity of Repeated Doses of ABvac40 in Patients With a-MCI or Vm-AD
Condition: Mild Cognitive Impairment; Alzheimer Disease
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Study type: Interventional
Phase: Phase 2

Summary: 
      Alzheimer's disease (AD) is the most common type of dementia, accounting for 50-75% of the
      estimated 47 million people with dementia worldwide. The amyloid cascade hypothesis of AD
      proposes that amyloid-β (Aβ) peptide accumulation in the brain, caused by an imbalance
      between Aβ production and clearance, is the initiating factor of a cascade ultimately leading
      to dementia.

      Aβ peptides are generated from sequential cleavage of the amyloid precursor protein (APP),
      including Aβ40 and Aβ42. Aβ40 is the predominant variant (90%) among the secreted Aβ forms
      and although Aβ42 is more hydrophobic and prone to aggregate, and Aβ42 oligomers are regarded
      to be the most neurotoxic species, Aβ40 can also produce highly toxic diffusible aggregates,
      which can be prevented in vitro by specific anti-Aβ40 antibodies.

      Several studies have proposed that a high concentration of Aβ40 in the brain distinguishes
      patients with AD from those who have senile plaques but are cognitively normal, pointing to
      the importance of Aβ40 in the onset of dementia. In keeping with this, previous studies have
      demonstrated that specific anti-Aβ40 antibodies label NFTs in the entorhinal cortex and the
      hippocampus of AD brains, and that these do not co-localize with tau NFTs, suggesting the
      presence of degenerating neuronal populations filled with C-terminal fragments of Aβx-40. In
      addition, Aβ40 is the main component of amyloid deposition around cerebral arteries causing
      cerebral amyloid angiopathy (CAA), which has a prevalence of about 80-90% in patients with AD
      (for more information see Lacosta et al. Alzheimer's Research & Therapy (2018) 10:12 DOI
      10.1186/s13195-018-0340-8).

      Considering those previous results suggesting that strategies targeting Aβ40 could represent
      novel disease-modifying therapies, we have developed ABvac40, the first active vaccine
      targeting the C-terminal end of the Aβ40 peptide.

      The purpose of this Phase II study is to confirm in patients with a-MCI or vm-AD the level of
      safety and tolerability obtained in the ABvac40 Phase I clinical trial in patients with
      mm-AD. In addition, the study is aimed to better characterize the immune response elicited by
      ABvac40 and to explore its effects on AD biomarkers.
    


Intervention name(s): ABvac40; Placebo
Intervention type(s): Biological; Biological
Intervention description(s): ABvac40 consists in a conjugate of Aβx-40 with a carrier protein (KLH) vehiculated in phosphate buffer containing 0.35% aluminium hydroxide as adjuvant.; Placebo consists in the vaccine's vehicle (phosphate buffer containing 0.35% aluminium hydroxide) without the conjugate.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment