Masitinib in Patients With Mild Alzheimer's Disease

NCT05564169 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: AB21004
• Study Type: interventional
• Target: 600
• Locations: 2 countries
• Sites: 9

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.

Conditions

Alzheimer Disease

Keywords

Alzheimer's Disease; Mast Cells; Microglia; Tyrosine kinase inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Absolute change from baseline in Mini-Mental State Examination (MMSE) at week 24

  24 weeks

• Absolute change from baseline in ADAS-Cog11 score at week 24

  24 weeks

• Absolute change from baseline in ADCS-ADL score

  48 weeks

• Clinical Responder rate

  24 weeks

• CIBIC-plus

  24 weeks

Study Arms (2)

Masitinib (4.5) & SOC

EXPERIMENTAL

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); Drug: Standard of care

Placebo & SOC

PLACEBO COMPARATOR

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; Drug: Standard of care

Interventions

Placebo DRUG

treatment per os

Also known as: Placebo Oral Tablet

Placebo & SOC

Masitinib (4.5) DRUG

Masitinib (titration to 4.5 mg/kg/day)

Also known as: AB1010

Masitinib (4.5) & SOC

Standard of care DRUG

Cholinesterase inhibitors (donepezil, rivastigmine or galantamine) and/or memantine

Masitinib (4.5) & SOC; Placebo & SOC

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Related to disease
• Patients with any other cause of dementia shown by MRI findings and neurological examination
• Systemic conditions known to cause dementia, e.g., hypothyroidism, untreated vitamin B12 or folic acid deficiency, niacin deficiency, neurosyphilis, HIV infection at screening visit.
• 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.
• 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.

Sponsors & Collaborators

• AB Science: lead

Study Sites (9)

Institut de la mémoire et Maladie d'Alzheimer, Hôpitaux Universitaires Pitié-Salpêtrière

Paris, France

Location

Hospital Universitario Nuestra Señora del Perpetuo Socorro de Albacete (Hospital Universitario Nuestra Señora del Perpétuo Socorro)

Albacete, Spain

Location

Ace Alzheimer Center Barcelona (Fundació ACE)

Barcelona, Spain

Location

Hospital Policlínico de Gipuzkoa

Donostia / San Sebastian, Spain

Location

Virgen de las Nieves University Hospital (Hospital Universitario Virgen de las Nieves)

Granada, Spain

Location

La Paz University Hospital (Hospital Universitario La Paz)

Madrid, Spain

Location

Hospital Clinico Universitario Virgen de la Arrixaca

Murcia, Spain

Location

Hospital Universitario de Navarra

Pamplona, Spain

Location

Complejo Asistencial de Zamora. Hospital Provincial de Zamora

Zamora, Spain

Location

Related Publications (3)

• 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.

  PMID: 21504563 BACKGROUND

• 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.

  PMID: 36849969 BACKGROUND

• 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.

  PMID: 32623401 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Interventions

masitinib; Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Bruno Dubois, MD, PhD

  Hôpital Universitaire Pitié-Salpêtrière, Paris, France

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Study Coordinator

CONTACT

+33(0)147200014; clinical@ab-science.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Computerized central randomization system using an external provider.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Double-blind, Placebo-controlled, Parallel group (1:1), Multicenter, Comparative study over 24 weeks with a 24-week extension period (all patients can enter the extension phase until week 48).

Study Record Dates

• First Submitted: September 29, 2022
• First Posted: October 3, 2022
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: October 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); ES (8)