Masitinib in Patients With Mild to Moderate Alzheimer's Disease

AB Science

Status and phase: Completed; Phase 3

Conditions: Alzheimer Disease

Treatments: Drug: Masitinib; Drug: Placebo; Drug: Standard of care

Study type: Interventional

Funder types: Industry

Identifiers

NCT01872598

AB09004

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 721 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria include:

1. Patient with dementia of Alzheimer's type, according to the Diagnostic and Statistical Manual of Mental Disorders criteria (DSM-IV)
2. 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)
3. Patient with MMSE ≥ 12 and ≤ 25 at baseline
4. 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:

1. Patient with any other cause of dementia not due to Alzheimer's disease.
2. 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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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721 participants in 5 patient groups, including a placebo group

Masitinib escalating dose

Experimental group

Description:

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

Treatment:

Drug: Standard of care

Drug: Masitinib

Masitinib fixed dose (4.5 mg/kg/day)

Experimental group

Description:

Participants receive masitinib at 4.5 mg/kg/day, given orally twice daily.

Treatment:

Drug: Standard of care

Drug: Masitinib

Masitinib fixed dose (3.0 mg/kg/day)

Experimental group

Description:

Participants receive masitinib at 3.0 mg/kg/day, given orally twice daily.

Treatment:

Drug: Standard of care

Drug: Masitinib

Placebo (escalating dose)

Placebo Comparator group

Description:

Participants receive placebo, given orally twice daily, with a matched dose escalation after 3 months of treatment

Treatment:

Drug: Standard of care

Drug: Placebo

Placebo (fixed dose)

Placebo Comparator group

Description:

Participants receive fixed dose placebo, given orally twice daily

Treatment:

Drug: Standard of care

Drug: Placebo