Last updated on July 2019

Safety and Immunogenicity of Repeated Doses of ABvac40 in Patients With a-MCI or Vm-AD

Brief description of study

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- (A) peptide accumulation in the brain, caused by an imbalance between A production and clearance, is the initiating factor of a cascade ultimately leading to dementia.

A peptides are generated from sequential cleavage of the amyloid precursor protein (APP), including A40 and A42. A40 is the predominant variant (90%) among the secreted A forms and although A42 is more hydrophobic and prone to aggregate, and A42 oligomers are regarded to be the most neurotoxic species, A40 can also produce highly toxic diffusible aggregates, which can be prevented in vitro by specific anti-A40 antibodies.

Several studies have proposed that a high concentration of A40 in the brain distinguishes patients with AD from those who have senile plaques but are cognitively normal, pointing to the importance of A40 in the onset of dementia. In keeping with this, previous studies have demonstrated that specific anti-A40 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 Ax-40. In addition, A40 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 A40 could represent novel disease-modifying therapies, we have developed ABvac40, the first active vaccine targeting the C-terminal end of the A40 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.

Clinical Study Identifier: NCT03461276

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