Masitinib in Patients With Mild Alzheimer's Disease

NCT ID: NCT05564169

Last Updated: 2025-10-03

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 600 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-06-30
• Study Completion Date: 2029-12-31

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.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: EXPERIMENTAL

Masitinib (4.5)

Intervention Type: DRUG

Masitinib (titration to 4.5 mg/kg/day)

Standard of care

Intervention Type: DRUG

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

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

treatment per os

Standard of care

Intervention Type: DRUG

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

Interventions

Placebo

treatment per os

Intervention Type: DRUG

Masitinib (4.5)

Masitinib (titration to 4.5 mg/kg/day)

Intervention Type: DRUG

Standard of care

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

Intervention Type: DRUG

Other Intervention Names

Placebo Oral Tablet; AB1010

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

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.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AB Science

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bruno Dubois, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Universitaire Pitié-Salpêtrière, Paris, France

Locations

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

Countries

France; Spain

Central Contacts

Clinical Study Coordinator

Role: CONTACT

clinical@ab-science.com

+33(0)147200014

References

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.

Reference Type: BACKGROUND

PMID: 21504563 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 36849969 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32623401 (View on PubMed)

Other Identifiers

AB21004

Identifier Type: -

Identifier Source: org_study_id