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Masitinib in Patients With Mild to Moderate Alzheimer's Disease

Primary Purpose

Alzheimer Disease

Status
Not yet recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Placebo
Masitinib (4.5)
Standard of care
Sponsored by
AB Science
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Disease focused on measuring Alzheimer's Disease, Mast Cells, Microglia, Tyrosine kinase inhibitor

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Institut de la mémoire et Maladie d'Alzheimer, Hôpitaux Universitaires Pitié-Salpêtrière
  • Hospital Universitario Nuestra Señora del Perpetuo Socorro de Albacete (Hospital Universitario Nuestra Señora del Perpétuo Socorro)
  • Ace Alzheimer Center Barcelona (Fundació ACE)
  • Hospital Policlínico de Gipuzkoa
  • Virgen de las Nieves University Hospital (Hospital Universitario Virgen de las Nieves)
  • La Paz University Hospital (Hospital Universitario La Paz)
  • Hospital Clinico Universitario Virgen de la Arrixaca
  • Hospital Universitario de Navarra
  • Complejo Asistencial de Zamora. Hospital Provincial de Zamora

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Masitinib (4.5) & SOC

Placebo & SOC

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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)
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)

Secondary Outcome Measures

Time to severe dementia (MMSE<10)
Mini-Mental State Examination (MMSE) (scores from 0 to 30, with lower scores indicating poorer cognitive performance)
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)
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)
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]).
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.
Absolute change from baseline in CDR
Clinical Dementia Rating (CDR), scores from 0 to 18, with higher scores indicating worse dementia

Full Information

First Posted
September 29, 2022
Last Updated
October 6, 2023
Sponsor
AB Science
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1. Study Identification

Unique Protocol Identification Number
NCT05564169
Brief Title
Masitinib in Patients With Mild to Moderate Alzheimer's Disease
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 2024 (Anticipated)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AB Science

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease
Keywords
Alzheimer's Disease, Mast Cells, Microglia, Tyrosine kinase inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Randomized, Double-blind, Placebo-controlled, Parallel group (1:1), Multicenter, Comparative study over 24 weeks with a 24-week extension period (all patients can enter the extension phase until week 48).
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Computerized central randomization system using an external provider.
Allocation
Randomized
Enrollment
600 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Masitinib (4.5) & SOC
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo & SOC
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo Oral Tablet
Intervention Description
treatment per os
Intervention Type
Drug
Intervention Name(s)
Masitinib (4.5)
Other Intervention Name(s)
AB1010
Intervention Description
Masitinib (titration to 4.5 mg/kg/day)
Intervention Type
Drug
Intervention Name(s)
Standard of care
Intervention Description
Cholinesterase inhibitors (donepezil, rivastigmine or galantamine) and/or memantine
Primary Outcome Measure Information:
Title
Absolute change from baseline in ADAS-Cog-11 score
Description
Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) (scores range from 0 to 70, with higher scores indicating worse dementia)
Time Frame
24 weeks
Title
Absolute change from baseline in ADCS-ADL score
Description
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
Secondary Outcome Measure Information:
Title
Time to severe dementia (MMSE<10)
Description
Mini-Mental State Examination (MMSE) (scores from 0 to 30, with lower scores indicating poorer cognitive performance)
Time Frame
48 weeks
Title
Absolute change from baseline in ADAS-Cog-11 score
Description
Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) (scores range from 0 to 70, with higher scores indicating worse dementia)
Time Frame
48 weeks
Title
Absolute change from baseline in ADCS-ADL score
Description
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
Title
Clinical Responder rate
Description
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
Title
CIBIC-plus
Description
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.
Time Frame
24 weeks
Title
Absolute change from baseline in CDR
Description
Clinical Dementia Rating (CDR), scores from 0 to 18, with higher scores indicating worse dementia
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Study Coordinator
Phone
+33(0)147200014
Email
clinical@ab-science.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruno Dubois, MD, PhD
Organizational Affiliation
Hôpital Universitaire Pitié-Salpêtrière, Paris, France
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut de la mémoire et Maladie d'Alzheimer, Hôpitaux Universitaires Pitié-Salpêtrière
City
Paris
Country
France
Facility Name
Hospital Universitario Nuestra Señora del Perpetuo Socorro de Albacete (Hospital Universitario Nuestra Señora del Perpétuo Socorro)
City
Albacete
Country
Spain
Facility Name
Ace Alzheimer Center Barcelona (Fundació ACE)
City
Barcelona
Country
Spain
Facility Name
Hospital Policlínico de Gipuzkoa
City
Donostia-San Sebastian
Country
Spain
Facility Name
Virgen de las Nieves University Hospital (Hospital Universitario Virgen de las Nieves)
City
Granada
Country
Spain
Facility Name
La Paz University Hospital (Hospital Universitario La Paz)
City
Madrid
Country
Spain
Facility Name
Hospital Clinico Universitario Virgen de la Arrixaca
City
Murcia
Country
Spain
Facility Name
Hospital Universitario de Navarra
City
Pamplona
Country
Spain
Facility Name
Complejo Asistencial de Zamora. Hospital Provincial de Zamora
City
Zamora
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
21504563
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.
Results Reference
background
PubMed Identifier
36849969
Citation
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.
Results Reference
background
PubMed Identifier
32623401
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.
Results Reference
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Masitinib in Patients With Mild to Moderate Alzheimer's Disease

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