Masitinib in Patients With Mild Alzheimer's Disease

Phase 3

Not yet recruiting

• Conditions: Alzheimer Disease
• Interventions: Drug: Placebo; Drug: Masitinib (4.5); Drug: Standard of care

• Registration Number: NCT05564169
• Lead Sponsor: AB Science

Brief Summary

Masitinib is an orally administered tyrosine kinase inhibitor that targets activated cells of the neuroimmune system (mast cells and microglia). Study AB21004 will evaluate masitinib as an adjunct to cholinesterase inhibitor and/or memantine in patients with mild-to-moderate Alzheimer's disease.

Detailed Description

Masitinib is an oral tyrosine kinase inhibitor that has demonstrated neuroprotective action in neurodegenerative diseases via inhibition of mast cell and microglia/macrophage activity, and which is capable of accumulating within the central nervous system (CNS) at a therapeutically relevant concentration. There is a growing body of evidence implicating mast cells and microglia (types of innate immune cells that are present in the CNS), with the pathophysiology of Alzheimer's disease.

Masitinib has been shown to restore normal spatial learning performance and promote recovery of synaptic markers in a mouse model of Alzheimer's disease, with its synapto-protective action being directly linked to mast cell inhibition. The potential benefit of masitinib in the treatment of patients with mild to moderate Alzheimer's disease has been previously demonstrated in a phase 2 study (AB04024; NCT00976118) and a positive phase 2B/3 study (AB09004; NCT01872598) that showed masitinib (4.5 mg/kg/day) was associated with a statistically significant slowing of cognitive deterioration.

The objective of study AB21004 is to confirm treatment effect with masitinib as an adjunct to cholinesterase inhibitor and/or memantine in patients with mild-to-moderate Alzheimer's disease.

Study Timeline

• Study First Submitted: 2022-09-29
• Study First Submitted QC: 2022-09-29
• Study First Posted: 2022-10-03
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-30
• Last Update Posted: 2025-10-03
• Study Start: 2026-06-01
• Primary Completion: 2028-12
• Study Completion: 2029-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo & SOC	Placebo	Participants receive a matched dose placebo, given orally twice daily. Placebo will be administered as an add-on to cholinesterase inhibitor and/or memantine standard of care (SOC).
Masitinib (4.5) & SOC	Masitinib (4.5)	Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment. Dose up-titration is subjected to a safety control. Masitinib will be administered as an add-on to cholinesterase inhibitor and/or memantine standard of care (SOC).
Masitinib (4.5) & SOC	Standard of care	Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment. Dose up-titration is subjected to a safety control. Masitinib will be administered as an add-on to cholinesterase inhibitor and/or memantine standard of care (SOC).
Placebo & SOC	Standard of care	Participants receive a matched dose placebo, given orally twice daily. Placebo will be administered as an add-on to cholinesterase inhibitor and/or memantine standard of care (SOC).

Primary Outcome Measures

Name	Time	Method
Absolute change from baseline in iADRS score at week 24	24 weeks	The iADRS is a linear combination of its two components: the ADAS-Cog11 and the ADCS-iADL. The iADRS is calculated as follows: iADRS = ADCS-iADL + (70 - ADAS-Cog11).; Lower scores on the iADRS indicate greater impairment; iADRS scores range from 0 to 129.

Secondary Outcome Measures

Name	Time	Method
Absolute change from baseline in Mini-Mental State Examination (MMSE) at week 24	24 weeks	Mini-Mental State Examination (MMSE) (scores from 0 to 30, with lower scores indicating poorer cognitive performance)
Absolute change from baseline in ADAS-Cog11 score at week 24	24 weeks	The global score, which is the sum of the 11 items, ranges from 0 to 70, with higher scores indicating greater cognitive impairment.
Absolute change from baseline in ADCS-ADL score	48 weeks	Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL) (scores from 0 to 78, with lower scores indicating worse function)
Clinical Responder rate	24 weeks	Clinical response defined as decrease from baseline at week 24 in ADAS-cog of ≥4, without deterioration in ADCS-ADL (ADCS-ADL change ≥ 0 between baseline and timepoint) or worsening in the CIBIC-plus scale (response CIBIC in 1-3\] or no change \[CIBIC in 4\]).
CIBIC-plus	24 weeks	Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), a seven-point categorical rating scale ranging from 1 (marked improved) to 7 (markedly worse) compared with baseline.
Absolute change from baseline in CDR	24 weeks	Clinical Dementia Rating (CDR), scores from 0 to 18, with higher scores indicating worse dementia
Time to severe dementia (MMSE<10)	24 weeks	Mini-Mental State Examination (MMSE) (scores from 0 to 30, with lower scores indicating poorer cognitive performance)
Absolute change from baseline in ADAS-Cog11 score at week 48	48 weeks	The global score, which is the sum of the 11 items, ranges from 0 to 70, with higher scores indicating greater cognitive impairment.
Absolute change from baseline in ADCS-ADL score at week 24	24 weeks	Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL) (scores from 0 to 78, with lower scores indicating worse function)
Absolute change from baseline in Neuropsychiatric Inventory (NPI) at week 24	24 weeks	Total NPI-12 score ranges from 0 to 144 (higher = more severe symptoms)

Trial Locations

Locations (9)

Institut de la mémoire et Maladie d'Alzheimer, Hôpitaux Universitaires Pitié-Salpêtrière; 🇫🇷 Paris, France

Hospital Universitario Nuestra Señora del Perpetuo Socorro de Albacete (Hospital Universitario Nuestra Señora del Perpétuo Socorro); 🇪🇸 Albacete, Spain

Ace Alzheimer Center Barcelona (Fundació ACE); 🇪🇸 Barcelona, Spain

Hospital Policlínico de Gipuzkoa; 🇪🇸 Donostia / San Sebastian, Spain

Virgen de las Nieves University Hospital (Hospital Universitario Virgen de las Nieves); 🇪🇸 Granada, Spain

La Paz University Hospital (Hospital Universitario La Paz); 🇪🇸 Madrid, Spain

Hospital Clinico Universitario Virgen de la Arrixaca; 🇪🇸 Murcia, Spain

Hospital Universitario de Navarra; 🇪🇸 Pamplona, Spain

Complejo Asistencial de Zamora. Hospital Provincial de Zamora; 🇪🇸 Zamora, Spain