mild to moderate Alzheimer’s disease MedDRA version: 12.1 Level: LLT Classification code 10012271 Term: Dementia Alzheimer's type
Conditions
Interventions
Product Name: mastinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Concentration unit: mg
Sponsors
AB Science
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patient 2. Age = 50 years, weight = 45 kg and Body Mass Index (BMI) > 18 at screening 3. Menopause = 2 years for female patient 4. Patient with dementia of Alzheimer's type, according to DSM-IV criteria 5. Patient with probable Alzheimer' disease according to NINCDS-ADRDA criteria 6. Patient with MMSE = 12 and = 25 at baseline 7. Patient 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 6 months at baseline, with no changes foreseen in therapy throughout the study 8. Patient with adequate organ function at screening and baseline: • Absolute Neutrophils Count (ANC) = 2 x 109/L • Hemoglobin = 10 g/dL • Platelets (PTL) = 100 x 109/L • AST/ALT = 2.5 ULN • Bilirubin = 1.5 ULN • Albuminemia = 1 x LLN • Urea = 1.5 x ULN • Creatinine clearance > 60 mL/min (Cockcroft and Gault formula) • Proteinuria =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patient with any other cause of dementia not due to Alzheimer's disease, based on specific examination including a brain neuro-imagery exam within the last 6 months : • Other central nervous condition 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 dementia 2. Patient with Alzheimer disease with delusions or delirium 3. Patient treated with any registered or putative cognitive/memory enhancer or disease modifier other than donepezil, galantamine, rivastigmine or memantine. (Patient taking Ginkgo Biloba can be enrolled providing it has been taken at a stable dose for at least 6 months). 4. Patient with evidence of psychosis and/or use of antipsychotic drugs at screening, or history of significant psychiatric disorder 5. Patient with active current bacterial, viral (including hepatitis B and C, HIV, EBV, CMV, herpes zoster), fungal, mycobacterium, protozoan, or other infection 6. Patient with history of infection requiring hospitalization within 2 weeks of screening 7. Patient presenting with cardiac disorders defined by at least one of the following conditions: • Patient with recent cardiac history (within 6 months) of: - Acute coronary syndrome - Acute heart failure (class III or IV of the NYHA classification) - Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death) • Patient with cardiac failure class III or IV of the NYHA classification • Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block) • Syncope without known aetiology within 3 months • Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension The absence of the described cardiac disorders should be documented. Otherwise, and in the absence of a visit to a cardiologist within 3 months prior to screening visit, the patient should visit a cardiologist between screening and baseline visits in order to evaluate these specific criteria. 8. Patient with chronic diarrhea 9. Patient presenting with oedemas 10. Patient with co existing dermatological disease (e.g. eczema, psoriasis) or history of skin allergy 11. Patient with 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. Patient with life expectancy < 1 year Previous medications: 13. Patient treated with any investigational agent within 4 weeks of screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective is to compare the efficacy and safety of oral masitinib 6 mg/kg/day in combination with cholinesterase inhibitors and/or memantine to placebo in combination with cholinesterase inhibitors and/or memantine in patients with mild-to-moderate Alzheimer’s disease. • Co-primary endpoints: - Effect on cognition and memory assessed by Alzheimer’s disease Assessment Scale (ADAS-Cog) at Week 24. - Effect on self-care and activities of daily living assessed by Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL) at Week 24. ;Secondary Objective: • Secondary endpoints: - ADAS-Cog at Week 8 and Week 12 - ADAS-Cog response and worsening rates at Week 8, Week 12 and Week 24 - ADCS-ADL at Week 8 and Week 12 - ADCS-ADL response and worsening rate at Week 8, Week 12 and Week 24 - Clinician’s Interview Based Impression of Change-plus (CIBIC-plus) at Week 8, Week 12 and Week 24 - Mini-Mental State Examination (MMSE) at Week 8, Week 12 and Week 24 - Neuropsychiatric Inventory (NPI) at Week 12 and Week 24 - Clinical Dementia Rating (CDR) at Week 12 and Week 24 - Clinical responder rate at Week 8, Week 12 and Week 24 - Resource Utilization in Dementia – Lite Questionnaire (RUD-Lite) at Week 12 and W week 24 - Safety: occurrence of Adverse Events (AE), changes on clinical examination including vital signs (blood pressure, pulse rate) and weight, ECG and laboratory exams (biochemistry, hematology and urinalysis) ;Primary end point(s): • Co-primary endpoints: - Effect on cognition and memory assessed by Alzheimer’s disease Assessment Scale (ADAS-Cog) at Week 24. - Effect on self-care and activities of daily living assessed by Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL) at Week 24. | — |
Countries
France, Spain
Outcome results
None listed