Alzheimer DiseasePhase 3NCT05564169
Masitinib in Patients With Mild Alzheimer's Disease
A Phase 3 study testing Masitinib (4.5) in people with Alzheimer Disease, run by AB Science at 9 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Masitinib (4.5)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 600 participants
- Where
- 9 sitesin 2 countries
- Study dates
- Jun 2026to Dec 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Main inclusion criteria include:
- Patient with clinical diagnosis of Alzheimer's disease based on criteria defined by IWG (International Working Group on Alzheimer's disease) at screening visit.
- Patients with ADCS-ADL score at screening visit and baseline visit < 73
- Patient with MMSE ≥ 21 and ≤ 25 at screening visit and baseline visit.
- 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.
- 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.
- 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.
- 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
- Patients with any other cause of dementia shown by MRI findings and neurological examination
- 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, 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.
- 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.
Trial locations and contacts
9 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
9 sites in 2 countries
Spain8 sites
Hospital Universitario Nuestra Señora del Perpetuo Socorro de Albacete (Hospital Universitario Nuestra Señora del Perpétuo Socorro)
Albacete
Ace Alzheimer Center Barcelona (Fundació ACE)
Barcelona
Hospital Policlínico de Gipuzkoa
Donostia / San Sebastian
Virgen de las Nieves University Hospital (Hospital Universitario Virgen de las Nieves)
Granada
La Paz University Hospital (Hospital Universitario La Paz)
Madrid
Hospital Clinico Universitario Virgen de la Arrixaca
Murcia
Hospital Universitario de Navarra
Pamplona
Complejo Asistencial de Zamora. Hospital Provincial de Zamora
Zamora
France1 site
Institut de la mémoire et Maladie d'Alzheimer, Hôpitaux Universitaires Pitié-Salpêtrière
Paris
About this study
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Phase 3 Clinical Trial to Evaluate the Safety and Efficacy of Masitinib as add-on Therapy in Patients With Mild Alzheimer's Disease, Treated With Standard of Care
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.
Read the 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.
- Conditions
- Alzheimer Disease
- Being tested
- Placebo, Masitinib (4.5), Standard of care
- Keywords
- Alzheimer's Disease, Mast Cells, Microglia, Tyrosine kinase inhibitor
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Also called Placebo Oral Tablet
treatment per os
Masitinib (4.5)Drug
Also called AB1010
Masitinib (titration to 4.5 mg/kg/day)
Standard of careDrug
Cholinesterase inhibitors (donepezil, rivastigmine or galantamine) and/or memantine
| Study group | Role | What they receive |
|---|---|---|
| Masitinib (4.5) & SOC | Experimental | 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). Receives: Drug: Masitinib (4.5); Drug: Standard of care |
| Placebo & SOC | Placebo comparator | 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). Receives: Drug: Placebo; Drug: Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 weeks
Secondary outcomes (10)
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)
Measured: 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.
Measured: 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)
Measured: 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]).
Measured: 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.
Measured: 24 weeks
Absolute change from baseline in CDR
Clinical Dementia Rating (CDR), scores from 0 to 18, with higher scores indicating worse dementia
Measured: 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)
Measured: 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.
Measured: 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)
Measured: 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)
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2022
- Study startJun 2026 (estimated)
- Primary completionDec 2028 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AB Science
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bruno Dubois, MD, PhD, Principal investigator, Hôpital Universitaire Pitié-Salpêtrière, Paris, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05564169
- Sponsor's protocol ID
- AB21004
- Status last verified
- Sep 2025
- First submitted
- 29 Sep 2022
- Last updated
- 3 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 21504563Dubois 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.
PubMed 36849969Li 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.
PubMed 32623401
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Phase 3 Clinical Trial to Evaluate the Safety and Efficacy of Masitinib as add-on Therapy in Patients With Mild Alzheimer's Disease, Treated With Standard of Care
- ClinicalTrials.gov ID
- NCT05564169
- Acronym / sponsor ID
- AB21004
- Conditions
- Alzheimer Disease
- Keywords
- Alzheimer's Disease, Mast Cells, Microglia, Tyrosine kinase inhibitor
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- AB ScienceIndustry (pharma, biotech, devices)
- Study start
- Jun 2026 (estimated)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 3 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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).
| Arm | Type | Receives |
|---|---|---|
| Masitinib (4.5) & SOC | Experimental | Drug: Masitinib (4.5), Drug: Standard of careParticipants 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 | Placebo comparator | Drug: Placebo, Drug: Standard of careParticipants 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). |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboAlso: Placebo Oral Tablettreatment per os | Drug | Placebo & SOC |
| Masitinib (4.5)Also: AB1010Masitinib (titration to 4.5 mg/kg/day) | Drug | Masitinib (4.5) & SOC |
| Standard of careCholinesterase inhibitors (donepezil, rivastigmine or galantamine) and/or memantine | Drug | Masitinib (4.5) & SOC, Placebo & SOC |
Primary outcome
Absolute change from baseline in iADRS score at week 24
Time frame: 24 weeks
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.
10 secondary outcomes
Absolute change from baseline in Mini-Mental State Examination (MMSE) at week 24
Time frame: 24 weeks
Absolute change from baseline in ADAS-Cog11 score at week 24
Time frame: 24 weeks
Absolute change from baseline in ADCS-ADL score
Time frame: 48 weeks
Clinical Responder rate
Time frame: 24 weeks
CIBIC-plus
Time frame: 24 weeks
Absolute change from baseline in CDR
Time frame: 24 weeks
Time to severe dementia (MMSE<10)
Time frame: 24 weeks
Absolute change from baseline in ADAS-Cog11 score at week 48
Time frame: 48 weeks
Absolute change from baseline in ADCS-ADL score at week 24
Time frame: 24 weeks
Absolute change from baseline in Neuropsychiatric Inventory (NPI) at week 24
Time frame: 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2025.
- Background: PubMed 21504563Piette 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.
- Background: PubMed 36849969Dubois 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.
- Background: PubMed 32623401Li 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Bruno Dubois, MD, PhD principal investigator
Hôpital Universitaire Pitié-Salpêtrière, Paris, France
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Masitinib (4.5) in people with Alzheimer Disease, run by AB Science at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 3 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Spain, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Study Coordinator (+33(0)147200014, clinical@ab-science.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absolute change from baseline in iADRS score at week 24 (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05564169, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2025.