Masitinib in Patients With Mild to Moderate Alzheimer's Disease
- Conditions
- Alzheimer Disease
- Interventions
- Registration Number
- NCT05564169
- Lead Sponsor
- AB Science
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 600
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo & SOC Placebo 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). Masitinib (4.5) & SOC Masitinib (4.5) 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). Masitinib (4.5) & SOC Standard of care 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). Placebo & SOC Standard of care 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).
- Primary Outcome Measures
Name Time Method Absolute change from baseline in ADCS-ADL score 24 weeks Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL) (scores from 0 to 78, with lower scores indicating worse function)
Absolute change from baseline in ADAS-Cog-11 score 24 weeks Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) (scores range from 0 to 70, with higher scores indicating worse dementia)
- Secondary Outcome Measures
Name Time Method Time to severe dementia (MMSE<10) 48 weeks Mini-Mental State Examination (MMSE) (scores from 0 to 30, with lower scores indicating poorer cognitive performance)
Absolute change from baseline in CDR 24 weeks Clinical Dementia Rating (CDR), scores from 0 to 18, with higher scores indicating worse dementia
Absolute change from baseline in ADAS-Cog-11 score 48 weeks Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) (scores range from 0 to 70, with higher scores indicating worse dementia)
Absolute change from baseline in ADCS-ADL score 48 weeks Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL) (scores from 0 to 78, with lower scores indicating worse function)
Clinical Responder rate 24 weeks 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 \[CIBIC in 4\]).
CIBIC-plus 24 weeks 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.
Trial Locations
- Locations (9)
Virgen de las Nieves University Hospital (Hospital Universitario Virgen de las Nieves)
🇪🇸Granada, Spain
Hospital Universitario de Navarra
🇪🇸Pamplona, Spain
Ace Alzheimer Center Barcelona (Fundació ACE)
🇪🇸Barcelona, Spain
Hospital Universitario Nuestra Señora del Perpetuo Socorro de Albacete (Hospital Universitario Nuestra Señora del Perpétuo Socorro)
🇪🇸Albacete, Spain
Institut de la mémoire et Maladie d'Alzheimer, Hôpitaux Universitaires Pitié-Salpêtrière
🇫🇷Paris, France
Hospital Policlínico de Gipuzkoa
🇪🇸Donostia-San Sebastian, Spain
La Paz University Hospital (Hospital Universitario La Paz)
🇪🇸Madrid, Spain
Complejo Asistencial de Zamora. Hospital Provincial de Zamora
🇪🇸Zamora, Spain
Hospital Clinico Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain