Activity of Masitinib (AB1010) in Mild to Moderate Alzheimer's Disease

• change from baseline in ADAS-Cog [ Time Frame: week 4 and 12 ] [ Designated as safety issue: No ]
• change from baseline in CIBIC-plus [ Time Frame: week 4, 8, 12 and 24 ] [ Designated as safety issue: No ]
• change from baseline in CDR [ Time Frame: week 12, 24 ] [ Designated as safety issue: No ]
• change from baseline in MMSE [ Time Frame: week 4, 12 and 24 ] [ Designated as safety issue: No ]
• change from baseline in NPI [ Time Frame: week 12 and 24 ] [ Designated as safety issue: No ]

This phase 2 study was designed to evaluate the activity of oral masitinib (AB1010) administered at 2 dose levels during 24 weeks to patients with mild to moderate confirmed Alzheimer's type disease.

• Drug: masitinib (AB1010)
  oral masitinib 3 or 6 mg/kg/day
  Other Name: AB1010
• Drug: placebo
  matching placebo to masitinib

• Placebo Comparator: placebo
  Intervention: Drug: placebo
• Experimental: oral masitinib (AB1010)
  masitinib (AB1010) 3 or 6 mg/kg/day
  Intervention: Drug: masitinib (AB1010)

Inclusion Criteria:

1. Outpatients from both sex
2. Age ≥ 50 years at screening
3. Menopause ≥ 2 years for women
4. Dementia of Alzheimer's type, according to DSM IV criteria
5. Probable Alzheimer' disease according to NINCDS-ADRDA criteria
6. MMSE ≥ 12 and ≤ 26 at baseline
7. CDR of 1 or 2 at baseline
8. Treated for a minimum of 6 months with a stable dose of cholinesterase inhibitors (donepezil, rivastigmine or galantamine) at baseline, and/or a stable dose of memantine for a minimum of 3 months at baseline, with no changes foreseen in therapy throughout the study
9. Presence of a reliable caregiver
10. Patient, identified caregiver and, if applicable, patient surrogate are able and willing to comply with study visits and procedures per protocol, understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed
11. Affiliated to the French Social Security regimen

Exclusion Criteria:

1. Any cause of dementia not due to Alzheimer's disease :

   • other central nervous conditions causing progressive deficits in memory and cognition, e.g. cerebrovascular disease, Parkinson's disease, Huntington's disease, brain tumor…
   • systemic conditions known to cause dementia, e.g., hypothyroidism, untreated vitamin B12 or folic acid deficiency, niacin deficiency, neurosyphilis, HIV infection…
   • substance-induced conditions
2. Alzheimer disease with delusions or delirium
3. Treatment with any registered or putative cognitive enhancer or disease modifier other than donepezil, galantamine, rivastigmine or memantine
4. Uncontrolled depression at screening
5. Evidence of psychosis and/or use of antipsychotic drugs at screening, or history of significant psychotic disorder or hospitalization for psychiatric disorders
6. Active current bacterial, viral (including hepatitis B and C, HIV, EBV, CMV, herpes zoster, herpes simplex), fungal, mycobacterium, protozoan, or other infection.
7. History of infection requiring hospitalization or treatment with antibiotics within 2 weeks of screening
8. Inadequate organ function, defined as follows : total bilirubin ≥ 1.5 x ULN, SGOT and SGPT ≥ 2.5 x UNL, creatinine clearance calculated by Crocroft method < 35 ml/mn, ANC ≤ 2500, platelets ≤ 100 000 at baseline
9. Treatment with any investigational agent within 4 weeks of screening,
10. Men and their partner refusing to use 2 methods of medically acceptable forms of contraception during the study.
11. History of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent
12. Any condition that, in the investigator's opinion, could be detrimental to subjects participating in this study as life expectancy < 1 year, or any clinically important deviations from normal clinical laboratory values or concurrent medical events.