Masitinib in Patients With Mild Alzheimer's Disease

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.

Interventions

• Placebo · DRUG

  treatment per os

• Masitinib (4.5) · DRUG

  Masitinib (titration to 4.5 mg/kg/day)

• Standard of care · DRUG

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

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

Main inclusion criteria include:

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.

Main exclusion criteria include:

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.

Sites (9)

• 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