MedDRA version: 20.0 Level: HLT Classification code 10001897 Term: Alzheimer's disease (incl subtypes) System Organ Class: 100000004852 MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852 MedDRA version: 24.1 Level: LLT Classification code 10086384 Term: Early onset Alzheimer's disease System Organ Class: 100000004852
Conditions
Sponsors
AB Science
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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; 2. Patient with ADCS-ADL score at screening visit and baseline visit 19pg/ml OR a p-tau/a-beta ratio > 0.024, as measured by a central laboratory according to the Elecsys assay for Cerebrospinal fluid (CSF) biomarkers; 5. 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; 6. 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; 7. Patients with a caregiver who, at screening visit and baseline visit: - Agrees to accompany the participant to all study visits and able to supervise the participant's compliance with the study procedures and provide detailed information about the participant. - Either lives with the participant or sees the participant on average for =1 hours/day =3 days/week, or in the Investigator's opinion, the extent of contact is sufficient to provide meaningful assessment of changes in participant behaviour and function over time and provide information on safety and tolerability. - Is able to read, understand, and speak the designated language at the study centre. - Caregiver must be cognitively able to fulfil the requirements of the study. Other inclusion criteria 8. Male or non-pregnant female adult =50 years of age at time of enrolment at screening visit; 9. Patients with bodyweight >45 kg and BMI between 18 and 35 kg/m2 at screening visit or baseline visit 10. Contraception, at screening and baseline visit: Female patients of childbearing potential (entering the study after a menstrual period and who has a negative pregnancy test), who agree to use a highly effective method of contraception and an effective method of contraception by their male partner during the study and for 3 months and a half after the last treatment intake Male patients with a female partner of childbearing potential who agree to use a highly effective method of contraception and an effective method of contraception by their female partner during the study and for 3 months and a half after the last treatment intake OR who agree to use an effective method of contraception and a highly effective method of contraception by their female partner during the study and for 3 months and a half after the last treatment intake. Highly effective and effective methods of contraception are detailed in the Appendix 1.1 of the protocol. 11. Subjects must be able and willing to comply, both at screening visit and at baseline visit, with study visits and procedures; 12. Subjects able to understand, sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures; 13. Subjects able to understand, and willing to follow the
Exclusion criteria
Exclusion criteria: 1. Patients with any other cause of dementia shown by MRI findings and neurological examination in the last 12 months prior to screening visit; 2. Systemic conditions known to cause dementia, e.g., hypothyroidism, untreated vitamin B12 or folic acid deficiency, niacin deficiency, neurosyphilis, HIV infection at screening visit; 3. Patients with substance-induced dementia at screening visit; 4. Patients with Alzheimer’s disease with delirium at screening visit; 5. Patients with severe forms of delusions (e.g, NPI-12 delusion score of 4 or more) at screening visit; 6. Patients with evidence of psychosis and/or use of antipsychotic drugs at screening, or history of significant psychiatric disorder at screening visit; 7. Patients with hypersensitivity to masitinib or its excipients at screening; 8. Patients with history (or family history) of drug-induced severe skin toxicities or reactions at screening or patients taking concomitant treatment or therapies associated with severe drug-induced skin toxicity; 9. Patients with history of severe bone marrow disorders such as agranulocytosis or aplasia, or with abnormal laboratory results from local laboratory assessments at screening and baseline defined as: - Neutropenia with ANC 2 ULN at baseline, or - Total bilirubin level >1.5 ULN at baseline, or - Both hepatic transaminase levels and total bilirubin level outside of the normal ranges at screening and baseline, or - Albuminemia 30 mg/dL (1+) on dipstick; in case of the proteinuria =1+ on the dipstick, 24 hours proteinuria must be >1.5 g/24 hours; 12. Patients with current or history of severe cardiovascular disease, assessed at screening: - Myocardial infarction - Unstable angina pectoris - Coronary revascularization procedure - Congestive heart failure of NYHA Class III or IV - Stroke, including a transient ischemic attack - Second degree or third-degree atrioventricular block not successfully treated with a pacemaker - Bi-fascicular block - QTc Fridericia interval > 450 milliseconds for males and > 470 milliseconds for females - Drug induced heart failure or ischemic heart disease - Radiotherapy induced cardiomyopathy - Family history of unexpected death of cardiovascular origin - Edema of cardiac origin and left ventricular ejaculation fraction =50%; 13. Patients, with two or more of the risk factors listed below assessed by a cardiologist at screening as Very High Risk (calculated SCORE* =10%.) according to the Systematic Coronary Risk Estimation (SCORE*): - Hypertension (uncontrolled) - Diabetes - Kidney disease - Current smoking (= 10 Pack-year: equivalent to 1 pack of 20 cigarettes for 10 years with the formula N (number of packs of 20 cigarettes smoked daily) × T (number years smoking)) Patients who stopped smoking 6 months prior to the evaluation, are not concerned. - Hyperchol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate whether masitinib treatment will show a significant improvement ADCS-ADL and ADAS-Cog versus placebo in the study patients.;Secondary Objective: The secondary objectives of the study are to evaluate the efficacy of masitinib compared with placebo on a range of clinical parameters of Alzheimer's disease. The secondary objectives also include the assessment of safety and tolerability of masitinib as compared to placebo in terms of adverse events, vital signs, physical examination, ECG, and clinical laboratory tests. ;Primary end point(s): The study has two following primary endpoints: •Absolute change from baseline in ADCS-ADL score at week 24 and •Absolute change from baseline in ADAS-Cog score at week 24;Timepoint(s) of evaluation of this end point: week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary endpoint consists of: • Time to severe dementia (MMSE<10) The secondary endpoints of the study are: • Absolute change from baseline in ADAS-Cog score at week 48 • Absolute change from baseline in ADCS-ADL score at week 48 • Clinical Responder rate at Week 24. • Clinician’s Interview Based Impression of Change-plus (CIBIC-plus) at Week 24 • Mini-Mental State Examination (MMSE) at Week 24 • Clinical Dementia Rating (CDR) at Week 24 • Neuropsychiatric Inventory (NPI) at Week 24 ;Timepoint(s) of evaluation of this end point: week 24, week 48 | — |
Countries
Argentina, Belgium, Bulgaria, Canada, Colombia, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Netherlands, Norway, Peru, Poland, Portugal, Romania, Russian Federation, Serbia, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Ukraine, United Kingdom, United States
Contacts
Public ContactAlain Moussy
AB Science
Outcome results
None listed