A multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 3 study to evaluate the safety and efficacy of masitinib as add-on therapy in patients with mild to moderate Alzheimer's disease, treated with standard of care
- Conditions
- MedDRA version: 20.0Level: HLTClassification code 10001897Term: Alzheimer's disease (incl subtypes)System Organ Class: 100000004852MedDRA version: 20.0Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 100000004852MedDRA version: 24.1Level: LLTClassification code 10086384Term: Early onset Alzheimer's diseaseSystem Organ Class: 100000004852Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2021-002179-21-PL
- Lead Sponsor
- AB Science
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 600
1.Patient with clinical diagnosis of Alzheimer's disease based on criteria defined by IWG (International Working Group) on Alzheimer’s disease at screening visit
2.Patients with ADCS-ADL score at screening visit and baseline visit < 73
3.Patient with MMSE = 14 and = 25 at screening visit and baseline visit
4.Patient with Alzheimer’s Disease biomarker profile at screening visit:
- A positive amyloid PET scan
- Alternatively, positive a-beta AND p-tau OR an abnormal p-tau/a-beta ratio in CSF analyses.
Before randomization, the results will be verified centrally.
5.If patients are treated with :
• cholinesterase inhibitors (donepezil, rivastigmine or galantamine)
•And/or memantine.
They should have been at stable dose 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) patients must have been taking it at stable dose for at least 4 months prior to screening visit
7.Patients with a caregiver who, at screening visit and baseline visit:
o 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.
o 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.
o Is able to read, understand, and speak the designated language at the study centre.
o 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 8 months 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 5 months after the last treatment intake.
Highly effective and effective methods of contraception are detailed in the Appendix 14.1 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 safety procedures mentioned on the patient card in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity, at screening and baseline visit. Patient card will be provi
1.Patients with any other cause of dementia shown by MRI findings and neurological examination.
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 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.ADAS-Cog and ADCS-ADL scores at screening and baseline not in line with medical history and/or unexplained significant improvement or decline in overall status on ADAS-Cog and ADCS-ADL at screening and baseline compared with previous status
8.Patients with hypersensitivity to masitinib or its excipients at screening
9.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
10.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:
oNeutropenia with ANC <1.5 × 109/L
oAnemia with Hgb <10 g/dl
oThrombocytopenia with platelet counts <75 × 109/L
11.Patients with history of severe hepatic disorders, such as viral hepatitis or steatohepatitis, and alcoholic steatosis, or with abnormal laboratory results defined as:
oHepatic transaminase levels >2 ULN at baseline, or
oTotal bilirubin level >1.5 ULN at baseline, or
oBoth hepatic transaminase levels and total bilirubin level outside of the normal ranges at screening and baseline, or
oAlbuminemia <1 × LLN at screening and baseline, or
oPatients with concomitant medication known to be associated with severe hepatotoxicity
12.Patients with pre-existing severe renal impairment, or with abnormal laboratory results at screening:
oCreatinine clearance <60 mL/min (Cockcroft and Gault formula) or
oProteinuria >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
13.Patients with current or history of severe cardiovascular disease, assessed at screening:
oMyocardial infarction
oUnstable angina pectoris
oCoronary revascularization procedure
oCongestive heart failure of NYHA Class III or IV
oStroke, including a transient ischemic attack
oSecond degree or third-degree atrioventricular block not successfully treated with a pacemaker
oBi-fascicular block
oQTc Fridericia interval > 450 milliseconds for males and > 470 milliseconds for females
oDrug induced heart failure or ischemic heart disease
oRadiotherapy induced cardiomyopathy
oFamily history of unexpected death of cardiovascular origin
oEdema of cardiac origin and left ventricular ejaculation fraction =50%
14.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*):
oHypertension (uncontrolled)
oDiabetes
oKidney disease
oCurrent smoking (= 10 Pack-year: equivalent to 1 pack of 20 cigarettes for 10 years with the formula N (number of packs of 20 c
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method