Masitinib in Patients With Mild to Moderate Alzheimer's Disease

Phase 3

Completed

• Conditions: Alzheimer Disease
• Interventions: Drug: Placebo; Drug: Masitinib; Drug: Standard of care

• Registration Number: NCT01872598
• Lead Sponsor: AB Science

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.

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 Timeline

• Study Start: 2012-01
• Study First Submitted: 2013-06-05
• Study First Submitted QC: 2013-06-06
• Study First Posted: 2013-06-07
• Primary Completion: 2020-12
• Study Completion: 2020-12
• Disposition First Submitted: 2020-12-07
• Disposition First Submitted QC: 2020-12-07
• Disposition First Posted: 2020-12-08
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-27
• Last Update Posted: 2023-09-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 721

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Masitinib fixed dose (4.5 mg/kg/day)	Standard of care	Participants receive masitinib at 4.5 mg/kg/day, given orally twice daily.
Placebo (escalating dose)	Placebo	Participants receive placebo, given orally twice daily, with a matched dose escalation after 3 months of treatment
Masitinib fixed dose (3.0 mg/kg/day)	Standard of care	Participants receive masitinib at 3.0 mg/kg/day, given orally twice daily.
Placebo (fixed dose)	Standard of care	Participants receive fixed dose placebo, given orally twice daily
Masitinib escalating dose	Standard of care	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
Placebo (escalating dose)	Standard of care	Participants receive placebo, given orally twice daily, with a matched dose escalation after 3 months of treatment
Placebo (fixed dose)	Placebo	Participants receive fixed dose placebo, given orally twice daily
Masitinib escalating dose	Masitinib	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
Masitinib fixed dose (4.5 mg/kg/day)	Masitinib	Participants receive masitinib at 4.5 mg/kg/day, given orally twice daily.
Masitinib fixed dose (3.0 mg/kg/day)	Masitinib	Participants receive masitinib at 3.0 mg/kg/day, given orally twice daily.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
CIBIC-plus	24 weeks	Clinician's Interview Based Impression of Change-plus (CIBIC-plus)
MMSE	24 weeks	Change in Mini Mental State Examination (MMSE)

Trial Locations

Locations (6)

MHAT Sveta Marina; 🇧🇬 Varna, Bulgaria

General Hospital of Thessaloniki; 🇬🇷 Thessaloniki, Greece

Centrum Zdrowia Stołeczna 7; 🇵🇱 Białystok, Poland

Spitalul Universitar de Urgenta Elias; 🇷🇴 Bucuresti, Romania

Hospital Universitario Ramón y Cajal; 🇪🇸 Madrid, Spain

Municipal Institution Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikov; 🇺🇦 Dnipropetrovsk, Ukraine