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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
600
treatment per os
Masitinib (titration to 4.5 mg/kg/day)
Cholinesterase inhibitors (donepezil, rivastigmine or galantamine) and/or memantine
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
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.
Time frame: 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)
Time frame: 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.
Time frame: 24 weeks
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)
Time frame: 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 \[CIBIC in 4\]).
Time frame: 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.
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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
Time frame: 24 weeks
Absolute change from baseline in CDR
Clinical Dementia Rating (CDR), scores from 0 to 18, with higher scores indicating worse dementia
Time frame: 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)
Time frame: 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.
Time frame: 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)
Time frame: 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)
Time frame: 24 weeks