Masitinib in Patients With Mild to Moderate Alzheimer's Disease

Masitinib is an orally administered tyrosine kinase inhibitor that targets activated cells of the neuroimmune system (mast cells and microglia). Study AB21004 will evaluate masitinib as an adjunct to cholinesterase inhibitor and/or memantine in patients with mild-to-moderate Alzheimer's disease.

Masitinib is an oral tyrosine kinase inhibitor that has demonstrated neuroprotective action in neurodegenerative diseases via inhibition of mast cell and microglia/macrophage activity, and which is capable of accumulating within the central nervous system (CNS) at a therapeutically relevant concentration. There is a growing body of evidence implicating mast cells and microglia (types of innate immune cells that are present in the CNS), with the pathophysiology of Alzheimer's disease.

Masitinib has been shown to restore normal spatial learning performance and promote recovery of synaptic markers in a mouse model of Alzheimer's disease, with its synapto-protective action being directly linked to mast cell inhibition. The potential benefit of masitinib in the treatment of patients with mild to moderate Alzheimer's disease has been previously demonstrated in a phase 2 study (AB04024; NCT00976118) and a positive phase 2B/3 study (AB09004; NCT01872598) that showed masitinib (4.5 mg/kg/day) was associated with a statistically significant slowing of cognitive deterioration.

The objective of study AB21004 is to confirm treatment effect with masitinib as an adjunct to cholinesterase inhibitor and/or memantine in patients with mild-to-moderate Alzheimer's disease.

Eligibility Criteria:
Main inclusion criteria include:

* Patient with clinical diagnosis of Alzheimer's disease based on the International Working Group criteria according to the European Guideline on the clinical investigation of medicines for the treatment of Alzheimer's disease (CPMP/EWP/553/95 Rev.2 - 2018) at screening visit
* Patient with MMSE ≥ 14 and ≤ 25 at screening visit and baseline visit
* Patient with Alzheimer's disease biomarker profile at screening visit
* Patients treated for a minimum of 6 months with a stable dose of cholinesterase inhibitors (donepezil, rivastigmine or galantamine) at baseline visit, and/or a stable dose of memantine for a minimum of 6 months at baseline visit, with no changes foreseen in therapy throughout the study
* If receiving a supplement for cognition (eg, gingko biloba, omega-3 polyunsaturated fatty acid, vitamin E, curcumin, souvenaid) must be taking a stable dose for at least 4 months prior to screening visit

Main exclusion criteria include:

* Patients with any other cause of dementia shown by MRI findings and neurological examination in the last 12 months prior to screening visit
* Systemic conditions known to cause dementia, e.g., hypothyroidism, untreated vitamin B12 or folic acid deficiency, niacin deficiency, neurosyphilis, HIV infection at screening visit
* Patients with substance-induced dementia at screening visit
* Patients with Alzheimer's disease with delirium at screening visit
* Patients with severe forms of delusions (e.g, NPI-12 delusion score of 4 or more) at screening visit
* Patients with evidence of psychosis and/or use of antipsychotic drugs at screening, or history of significant psychiatric disorder at screening visit