Masitinib in Patients With Mild Alzheimer's Disease

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Phase 3 Clinical Trial to Evaluate the Safety and Efficacy of Masitinib as add-on Therapy in Patients With Mild Alzheimer's Disease, Treated With Standard of Care

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Masitinib (4.5); Drug: Placebo; Drug: Standard of care

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 Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Study Coordinator; Phone Number: +33(0)147200014; Email: clinical@ab-science.com

Study Locations

• France
  • Paris, France
    • Institut de la mémoire et Maladie d'Alzheimer, Hôpitaux Universitaires Pitié-Salpêtrière
• Spain
  • Albacete, Spain
    • Hospital Universitario Nuestra Señora del Perpetuo Socorro de Albacete (Hospital Universitario Nuestra Señora del Perpétuo Socorro)
  • Barcelona, Spain
    • Ace Alzheimer Center Barcelona (Fundació ACE)
  • Donostia / San Sebastian, Spain
    • Hospital Policlínico de Gipuzkoa
  • Granada, Spain
    • Virgen de las Nieves University Hospital (Hospital Universitario Virgen de las Nieves)
  • Madrid, Spain
    • La Paz University Hospital (Hospital Universitario La Paz)
  • Murcia, Spain
    • Hospital Clinico Universitario Virgen de la Arrixaca
  • Pamplona, Spain
    • Hospital Universitario de Navarra
  • Zamora, Spain
    • Complejo Asistencial de Zamora. Hospital Provincial de Zamora

Participation Criteria

Eligibility Criteria

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

Description

Main inclusion criteria include:

1. Patient with clinical diagnosis of Alzheimer's disease based on criteria defined by IWG (International Working Group on Alzheimer's disease) at screening visit.
2. Patients with ADCS-ADL score at screening visit and baseline visit < 73
3. Patient with MMSE ≥ 21 and ≤ 25 at screening visit and baseline visit.

4. Patient with Alzheimer's Disease biomarker profile at screening visit:

   • A positive amyloid PET scan
   • Alternatively, positive a-beta AND p-tau results OR an abnormal p-tau/a-beta ratio in CSF analysis. Before randomization, the results will be verified centrally.
5. If patients are treated with cholinesterase inhibitors (donepezil, rivastigmine or galantamine), and/or memantine. They should have been at stable dose for a minimum of 6 months at baseline visit, with no changes foreseen in therapy throughout the trial.
6. If receiving a supplement for cognition (eg, gingko biloba, omega-3 polyunsaturated fatty acid, vitamin E, curcumin, souvenaid) patients must have been taking it at stable dose for at least 4 months prior to screening visit.
7. Patients with a caregiver who, at screening and baseline visits, agrees to accompany the participant to all trial visits, supervise compliance with procedures, provide detailed information, has sufficient contact (≥1 hour/day for ≥3 days/week or as deemed sufficient by the Investigator), can read, understand, and speak the designated language, and is cognitively capable of fulfilling trial requirements.

Main exclusion criteria include:

Related to disease

1. Patients with any other cause of dementia shown by MRI findings and neurological examination
2. Systemic conditions known to cause dementia, e.g., hypothyroidism, untreated vitamin B12 or folic acid deficiency, niacin deficiency, neurosyphilis, HIV infection at screening visit.
3. Patients with substance-induced dementia, Alzheimer's disease with delirium, severe delusions (e.g., NPI delusion score ≥ 4), psychosis or antipsychotic use, or a history of significant psychiatric disorders at the screening visit.
4. Patients with a significant unexplained improvement or decline in overall status on ADAS-Cog and ADCS-ADL at screening and baseline compared to previous assessments, and those whose scores are not in line with their medical history.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Masitinib (4.5) & SOC; 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).	Drug: Masitinib (4.5); Masitinib (titration to 4.5 mg/kg/day); Other Names: AB1010; Drug: Standard of care; Cholinesterase inhibitors (donepezil, rivastigmine or galantamine) and/or memantine
Placebo Comparator: Placebo & SOC; 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).	Drug: Placebo; treatment per os; Other Names: Placebo Oral Tablet; Drug: Standard of care; Cholinesterase inhibitors (donepezil, rivastigmine or galantamine) and/or memantine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change from baseline in iADRS score at week 24	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.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change from baseline in ADCS-ADL score	Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL) (scores from 0 to 78, with lower scores indicating worse function)	48 weeks
Clinical Responder rate	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]).	24 weeks
CIBIC-plus	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.	24 weeks
Absolute change from baseline in CDR	Clinical Dementia Rating (CDR), scores from 0 to 18, with higher scores indicating worse dementia	24 weeks
Absolute change from baseline in Mini-Mental State Examination (MMSE) at week 24	Mini-Mental State Examination (MMSE) (scores from 0 to 30, with lower scores indicating poorer cognitive performance)	24 weeks
Absolute change from baseline in ADAS-Cog11 score at week 24	The global score, which is the sum of the 11 items, ranges from 0 to 70, with higher scores indicating greater cognitive impairment.	24 weeks
Time to severe dementia (MMSE<10)	Mini-Mental State Examination (MMSE) (scores from 0 to 30, with lower scores indicating poorer cognitive performance)	24 weeks
Absolute change from baseline in ADAS-Cog11 score at week 48	The global score, which is the sum of the 11 items, ranges from 0 to 70, with higher scores indicating greater cognitive impairment.	48 weeks
Absolute change from baseline in ADCS-ADL score at week 24	Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL) (scores from 0 to 78, with lower scores indicating worse function)	24 weeks
Absolute change from baseline in Neuropsychiatric Inventory (NPI) at week 24	Total NPI-12 score ranges from 0 to 144 (higher = more severe symptoms)	24 weeks

Collaborators and Investigators

• Sponsor: AB Science
• Investigators: Principal Investigator: Bruno Dubois, MD, PhD, Hôpital Universitaire Pitié-Salpêtrière, Paris, France

Publications and helpful links

General Publications

• Piette F, Belmin J, Vincent H, Schmidt N, Pariel S, Verny M, Marquis C, Mely J, Hugonot-Diener L, Kinet JP, Dubreuil P, Moussy A, Hermine O. Masitinib as an adjunct therapy for mild-to-moderate Alzheimer's disease: a randomised, placebo-controlled phase 2 trial. Alzheimers Res Ther. 2011 Apr 19;3(2):16. doi: 10.1186/alzrt75.
• Li T, Martin E, Abada YS, Boucher C, Ces A, Youssef I, Fenaux G, Forand Y, Legrand A, Nachiket N, Dhenain M, Hermine O, Dubreuil P, Delarasse C, Delatour B. Effects of Chronic Masitinib Treatment in APPswe/PSEN1dE9 Transgenic Mice Modeling Alzheimer's Disease. J Alzheimers Dis. 2020;76(4):1339-1345. doi: 10.3233/JAD-200466.
• Dubois B, Lopez-Arrieta J, Lipschitz S, Doskas T, Spiru L, Moroz S, Venger O, Vermersch P, Moussy A, Mansfield CD, Hermine O, Tsolaki M; AB09004 Study Group Investigators. Masitinib for mild-to-moderate Alzheimer's disease: results from a randomized, placebo-controlled, phase 3, clinical trial. Alzheimers Res Ther. 2023 Feb 28;15(1):39. doi: 10.1186/s13195-023-01169-x.

Helpful Links

• Li T, Martin E, Abada YS, et al. Effects of Chronic Masitinib Treatment in APPswe/PSEN1dE9 Transgenic Mice Modeling Alzheimer's Disease. J Alzheimers Dis. 2020;76(4):1339-1345. doi:10.3233/JAD-200466

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: September 29, 2022
• First Submitted That Met QC Criteria: September 29, 2022
• First Posted (Actual): October 3, 2022

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: September 30, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Tyrosine kinase inhibitor; Microglia; Mast Cells
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care; masitinib
• Other Study ID Numbers: AB21004; 2021-002179-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No