Masitinib in Patients With Mild to Moderate Alzheimer's Disease

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy of masitinib for the treatment of mild to moderate Alzheimer's Disease. Masitinib will be administered as add-on therapy in patients who have been treated for a minimum of 6 months with a stable dose of cholinesterase inhibitor (donepezil, rivastigmine or galantamine) and/or memantine.

Detailed Description
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Actual standard treatment for mild to moderately severe Alzheimer's dementia includes acetylcholinesterase inhibitors (donepezil, rivastigmine and galantamine) and a NMDA receptor antagonist (memantine for moderate to severe Alzheimer's disease). These medications have shown to have an effect on some cognitive and non cognitive symptoms of the pathology. However, their efficacy remains limited and may decrease with time. There is an unmet medical need in this pathology. Masitinib is a selective tyrosine kinase inhibitor that is thought to exert a neuroprotective effect through its activity on mast cells and other non-neuronal cells of the central nervous system, with subsequent modulation of inflammatory and neurodegenerative processes, as well as possibly disruption of the Aβ signaling cascade via inhibition of the Fyn signaling pathway. This is a multicenter, double-blind, randomized, placebo-controlled, parallel-group study of oral masitinib. The objective of this study is to compare the efficacy and safety of masitinib at various doses versus matched placebo in the treatment of patients with mild to moderate Alzheimer's Disease. Masitinib will be administered as add-on therapy in patients who have been treated for a minimum of 6 months with a stable dose of cholinesterase inhibitor (donepezil, rivastigmine or galantamine) and/or memantine. Approximately 675 patients will be randomized into 5 treatment groups. The co-primary outcome measures are the Alzheimer's Disease Cooperative Study Activities of Daily Living score (ADCS-ADL), and Alzheimer's Disease Assessment Scale-Cognitive Subscale score (ADAS-Cog) after 24 weeks of treatment.

Official Title
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A Multicenter, Double-blind, Placebo-controlled, Randomized, Parallel-group Phase 3 Study to Evaluate the Safety and Efficacy of Masitinib in Patients With Mild to Moderate Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: Masitinib
* Drug: Placebo
* Drug: Standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion criteria include: Patient with dementia of Alzheimer's type, according to the Diagnostic and Statistical Manual of Mental Disorders criteria (DSM-IV) Patient with probable Alzheimer' disease according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria (NINCDS-ADRDA) Patient with MMSE ≥ 12 and ≤ 25 at baseline 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. Exclusion criteria include: Patient with any other cause of dementia not due to Alzheimer's disease. Patient with Alzheimer disease with severe forms of delusions or delirium (patients with light and mild forms of delusions and delirium will be allowed in the study).

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Masitinib escalating dose<br>Participants receive masitinib at 4.5 mg/kg/day, given orally twice daily, with a dose escalation to 6 mg/kg/day after 3 months of treatment | Drug: Masitinib<br> <br> * Other names: AB1010;Drug: Standard of care<br>* stable dose of cholinesterase inhibitor (donepezil, rivastigmine or galantamine) and/or memantine, as per standard practice.<br>|
| Experimental: Masitinib fixed dose (4.5 mg/kg/day)<br>Participants receive masitinib at 4.5 mg/kg/day, given orally twice daily. | Drug: Masitinib<br> <br> * Other names: AB1010;Drug: Standard of care<br>* stable dose of cholinesterase inhibitor (donepezil, rivastigmine or galantamine) and/or memantine, as per standard practice.<br>|
| Experimental: Masitinib fixed dose (3.0 mg/kg/day)<br>Participants receive masitinib at 3.0 mg/kg/day, given orally twice daily. | Drug: Masitinib<br> <br> * Other names: AB1010;Drug: Standard of care<br>* stable dose of cholinesterase inhibitor (donepezil, rivastigmine or galantamine) and/or memantine, as per standard practice.<br>|
| Placebo Comparator: Placebo (escalating dose)<br>Participants receive placebo, given orally twice daily, with a matched dose escalation after 3 months of treatment | Drug: Placebo<br> <br> * Other names: Placebo Oral Tablet;Drug: Standard of care<br>* stable dose of cholinesterase inhibitor (donepezil, rivastigmine or galantamine) and/or memantine, as per standard practice.<br>|
| Placebo Comparator: Placebo (fixed dose)<br>Participants receive fixed dose placebo, given orally twice daily | Drug: Placebo<br> <br> * Other names: Placebo Oral Tablet;Drug: Standard of care<br>* stable dose of cholinesterase inhibitor (donepezil, rivastigmine or galantamine) and/or memantine, as per standard practice.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ADCS-ADL | Change in the Alzheimer's Disease Cooperative Study Activities of Daily Living score (ADCS-ADL). | 24 weeks | 
| ADAS-Cog | Change in the Alzheimer's Disease Assessment Scale-Cognitive Subscale score (ADAS-Cog). | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MMSE | Change in Mini Mental State Examination (MMSE) | 24 weeks | 
| CIBIC-plus | Clinician's Interview Based Impression of Change-plus (CIBIC-plus) | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer, dementia, cognitive disease, memory loss, cerebrovascular disease, tyrosine kinase inhibitor