Masitinib in Patients With Mild to Moderate Alzheimer's Disease

• ClinicalTrials.gov Identifier: NCT01872598
• Recruitment Status: Completed
• First Posted: June 7, 2013
• Last Update Posted: February 13, 2023
• Sponsor: AB Science
• Information provided by (Responsible Party): AB Science

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer Disease	Drug: Masitinib; Drug: Placebo; Drug: Standard of care	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 721 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 2012
• Actual Primary Completion Date: December 2020
• Actual Study Completion Date: December 2020

Arms and Interventions

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 Name: AB1010; Drug: Standard of care; Masitinib and placebo will be administered as add-on therapy in patients who are receiving a 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 Name: AB1010; Drug: Standard of care; Masitinib and placebo will be administered as add-on therapy in patients who are receiving a 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 Name: AB1010; Drug: Standard of care; Masitinib and placebo will be administered as add-on therapy in patients who are receiving a 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 Name: Placebo Oral Tablet; Drug: Standard of care; Masitinib and placebo will be administered as add-on therapy in patients who are receiving a 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 Name: Placebo Oral Tablet; Drug: Standard of care; Masitinib and placebo will be administered as add-on therapy in patients who are receiving a stable dose of cholinesterase inhibitor (donepezil, rivastigmine or galantamine) and/or memantine, as per standard practice.

Outcome Measures

Primary Outcome Measures :

1. ADCS-ADL [ Time Frame: 24 weeks ]
   Change in the Alzheimer's Disease Cooperative Study Activities of Daily Living score (ADCS-ADL).
2. ADAS-Cog [ Time Frame: 24 weeks ]
   Change in the Alzheimer's Disease Assessment Scale-Cognitive Subscale score (ADAS-Cog).

Secondary Outcome Measures :

1. MMSE [ Time Frame: 24 weeks ]
   Change in Mini Mental State Examination (MMSE)
2. CIBIC-plus [ Time Frame: 24 weeks ]
   Clinician's Interview Based Impression of Change-plus (CIBIC-plus)

Eligibility Criteria

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

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).

Contacts and Locations

Locations

Bulgaria

MHAT Sveta Marina

Varna, Bulgaria, 9010

Greece

General Hospital of Thessaloniki

Thessaloniki, Greece, 570 10

Poland

Centrum Zdrowia Stołeczna 7

Białystok, Poland, 15-879

Romania

Spitalul Universitar de Urgenta Elias

Bucuresti, Romania, 013686

Spain

Hospital Universitario Ramón y Cajal

Madrid, Spain, 28034

Ukraine

Municipal Institution Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikov

Dnipropetrovsk, Ukraine, 49005

Sponsors and Collaborators

AB Science

Investigators

• Principal Investigator: Bruno DUBOIS, M.D., Ph.D.; Pitié-Salpétrière

More Information

• Responsible Party: AB Science
• ClinicalTrials.gov Identifier: NCT01872598
• Other Study ID Numbers: AB09004
• First Posted: June 7, 2013
• Last Update Posted: February 13, 2023
• Last Verified: February 2023

Keywords provided by AB Science:

Alzheimer; dementia; cognitive disease; memory loss; cerebrovascular disease; tyrosine kinase inhibitor

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders