Masitinib in Patients With Mild to Moderate Alzheimer's Disease

Alzheimer Disease Clinical Trial

Official title:

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Phase 3 Study of Masitinib as add-on Therapy in Patients With Mild to Moderate Alzheimer's Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05564169
• Other study ID #: AB21004
• Secondary ID: 2021-002179-21
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: January 2024
• Est. completion date: December 2026

Study information

• Verified date: October 2023
• Source: AB Science
• Contact: Clinical Study Coordinator
• Phone: +33(0)147200014
• Email: clinical[@]ab-science.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 600
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Main inclusion criteria include:

• Patient with clinical diagnosis of Alzheimer's disease based on the International Working Group criteria according to the European Guideline on the clinical investigation of medicines for the treatment of Alzheimer's disease (CPMP/EWP/553/95 Rev.2 - 2018) at screening visit
• Patient with MMSE = 14 and = 25 at screening visit and baseline visit
• Patient with Alzheimer's disease biomarker profile at screening visit
• Patients treated for a minimum of 6 months with a stable dose of cholinesterase inhibitors (donepezil, rivastigmine or galantamine) at baseline visit, and/or a stable dose of memantine for a minimum of 6 months at baseline visit, with no changes foreseen in therapy throughout the study
• If receiving a supplement for cognition (eg, gingko biloba, omega-3 polyunsaturated fatty acid, vitamin E, curcumin, souvenaid) must be taking a stable dose for at least 4 months prior to screening visit

Main exclusion criteria include:

• Patients with any other cause of dementia shown by MRI findings and neurological examination in the last 12 months prior to screening visit
• 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 at screening visit
• Patients with Alzheimer's disease with delirium at screening visit
• Patients with severe forms of delusions (e.g, NPI-12 delusion score of 4 or more) at screening visit
• Patients with evidence of psychosis and/or use of antipsychotic drugs at screening, or history of significant psychiatric disorder at screening visit

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• Placebo
treatment per os
• Masitinib (4.5)
Masitinib (titration to 4.5 mg/kg/day)
• Standard of care
Cholinesterase inhibitors (donepezil, rivastigmine or galantamine) and/or memantine

Locations

Country	Name	City	State
France	Institut de la mémoire et Maladie d'Alzheimer, Hôpitaux Universitaires Pitié-Salpêtrière	Paris
Spain	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

Sponsors (1)

Lead Sponsor	Collaborator
AB Science

Countries where clinical trial is conducted

France,  Spain, 

References & Publications (3)

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. Erratum In: Alzheimers Res Ther. 2023 Apr 22;15(1):85. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute change from baseline in ADAS-Cog-11 score	Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) (scores range from 0 to 70, with higher scores indicating worse dementia)	24 weeks
Primary	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)	24 weeks
Secondary	Time to severe dementia (MMSE<10)	Mini-Mental State Examination (MMSE) (scores from 0 to 30, with lower scores indicating poorer cognitive performance)	48 weeks
Secondary	Absolute change from baseline in ADAS-Cog-11 score	Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) (scores range from 0 to 70, with higher scores indicating worse dementia)	48 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	Absolute change from baseline in CDR	Clinical Dementia Rating (CDR), scores from 0 to 18, with higher scores indicating worse dementia	24 weeks