Masitinib in Patients With Mild to Moderate Alzheimer's Disease

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Placebo; Drug: Masitinib; Drug: Standard of care

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 721
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Varna, Bulgaria, 9010
    • MHAT Sveta Marina
• Greece
  • Thessaloniki, Greece, 570 10
    • General Hospital of Thessaloniki
• Poland
  • Białystok, Poland, 15-879
    • Centrum Zdrowia Stołeczna 7
• Romania
  • Bucuresti, Romania, 013686
    • Spitalul Universitar de Urgenta Elias
• Spain
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
• Ukraine
  • Dnipropetrovsk, Ukraine, 49005
    • Municipal Institution Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AB Science
• Investigators: Principal Investigator: Bruno DUBOIS, M.D., Ph.D., Pitié-Salpetrière

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2012
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: June 5, 2013
• First Submitted That Met QC Criteria: June 6, 2013
• First Posted (Estimated): June 7, 2013

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: dementia; tyrosine kinase inhibitor; Alzheimer; memory loss; cerebrovascular disease; cognitive disease
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: AB09004