Ignite Creation Date:
2025-12-24 @ 10:52 PM
Ignite Modification Date:
2025-12-25 @ 8:21 PM
Study NCT ID:
NCT05564169
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-10-03
First Post:
2022-09-29
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Masitinib in Patients With Mild Alzheimer's Disease
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000544', 'term': 'Alzheimer Disease'}], 'ancestors': [{'id': 'D003704', 'term': 'Dementia'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D024801', 'term': 'Tauopathies'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'D019965', 'term': 'Neurocognitive Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C526575', 'term': 'masitinib'}, {'id': 'D059039', 'term': 'Standard of Care'}], 'ancestors': [{'id': 'D019984', 'term': 'Quality Indicators, Health Care'}, {'id': 'D011787', 'term': 'Quality of Health Care'}, {'id': 'D006298', 'term': 'Health Services Administration'}, {'id': 'D017530', 'term': 'Health Care Quality, Access, and Evaluation'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Computerized central randomization system using an external provider.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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).'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 600}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-06', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-09', 'completionDateStruct': {'date': '2029-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-09-30', 'studyFirstSubmitDate': '2022-09-29', 'studyFirstSubmitQcDate': '2022-09-29', 'lastUpdatePostDateStruct': {'date': '2025-10-03', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2022-10-03', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Absolute change from baseline in iADRS score at week 24', 'timeFrame': '24 weeks', 'description': '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).\n\nLower scores on the iADRS indicate greater impairment; iADRS scores range from 0 to 129.'}], 'secondaryOutcomes': [{'measure': 'Absolute change from baseline in Mini-Mental State Examination (MMSE) at week 24', 'timeFrame': '24 weeks', 'description': 'Mini-Mental State Examination (MMSE) (scores from 0 to 30, with lower scores indicating poorer cognitive performance)'}, {'measure': 'Absolute change from baseline in ADAS-Cog11 score at week 24', 'timeFrame': '24 weeks', 'description': 'The global score, which is the sum of the 11 items, ranges from 0 to 70, with higher scores indicating greater cognitive impairment.'}, {'measure': 'Absolute change from baseline in ADCS-ADL score', 'timeFrame': '48 weeks', '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)"}, {'measure': 'Clinical Responder rate', 'timeFrame': '24 weeks', '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\\]).'}, {'measure': 'CIBIC-plus', 'timeFrame': '24 weeks', '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."}, {'measure': 'Absolute change from baseline in CDR', 'timeFrame': '24 weeks', 'description': 'Clinical Dementia Rating (CDR), scores from 0 to 18, with higher scores indicating worse dementia'}, {'measure': 'Time to severe dementia (MMSE<10)', 'timeFrame': '24 weeks', 'description': 'Mini-Mental State Examination (MMSE) (scores from 0 to 30, with lower scores indicating poorer cognitive performance)'}, {'measure': 'Absolute change from baseline in ADAS-Cog11 score at week 48', 'timeFrame': '48 weeks', 'description': 'The global score, which is the sum of the 11 items, ranges from 0 to 70, with higher scores indicating greater cognitive impairment.'}, {'measure': 'Absolute change from baseline in ADCS-ADL score at week 24', 'timeFrame': '24 weeks', '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)"}, {'measure': 'Absolute change from baseline in Neuropsychiatric Inventory (NPI) at week 24', 'timeFrame': '24 weeks', 'description': 'Total NPI-12 score ranges from 0 to 144 (higher = more severe symptoms)'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ["Alzheimer's Disease", 'Mast Cells', 'Microglia', 'Tyrosine kinase inhibitor'], 'conditions': ['Alzheimer Disease']}, 'referencesModule': {'references': [{'pmid': '21504563', 'type': 'BACKGROUND', '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."}, {'pmid': '36849969', 'type': 'BACKGROUND', '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."}, {'pmid': '32623401', 'type': 'BACKGROUND', '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."}]}, 'descriptionModule': {'briefSummary': "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.", 'detailedDescription': "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.\n\nMasitinib 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.\n\nThe 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."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '50 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Main inclusion criteria include:\n\n1. Patient with clinical diagnosis of Alzheimer's disease based on criteria defined by IWG (International Working Group on Alzheimer's disease) at screening visit.\n2. Patients with ADCS-ADL score at screening visit and baseline visit \\< 73\n3. Patient with MMSE ≥ 21 and ≤ 25 at screening visit and baseline visit.\n4. Patient with Alzheimer's Disease biomarker profile at screening visit:\n\n * A positive amyloid PET scan\n * 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.\n5. 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.\n6. 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.\n7. 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.\n\nMain exclusion criteria include:\n\nRelated to disease\n\n1. Patients with any other cause of dementia shown by MRI findings and neurological examination\n2. Systemic conditions known to cause dementia, e.g., hypothyroidism, untreated vitamin B12 or folic acid deficiency, niacin deficiency, neurosyphilis, HIV infection at screening visit.\n3. 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.\n4. 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."}, 'identificationModule': {'nctId': 'NCT05564169', 'briefTitle': "Masitinib in Patients With Mild Alzheimer's Disease", 'organization': {'class': 'INDUSTRY', 'fullName': 'AB Science'}, 'officialTitle': "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", 'orgStudyIdInfo': {'id': 'AB21004'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Masitinib (4.5) & SOC', '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).', 'interventionNames': ['Drug: Masitinib (4.5)', 'Drug: Standard of care']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo & SOC', '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).', 'interventionNames': ['Drug: Placebo', 'Drug: Standard of care']}], 'interventions': [{'name': 'Placebo', 'type': 'DRUG', 'otherNames': ['Placebo Oral Tablet'], 'description': 'treatment per os', 'armGroupLabels': ['Placebo & SOC']}, {'name': 'Masitinib (4.5)', 'type': 'DRUG', 'otherNames': ['AB1010'], 'description': 'Masitinib (titration to 4.5 mg/kg/day)', 'armGroupLabels': ['Masitinib (4.5) & SOC']}, {'name': 'Standard of care', 'type': 'DRUG', 'description': 'Cholinesterase inhibitors (donepezil, rivastigmine or galantamine) and/or memantine', 'armGroupLabels': ['Masitinib (4.5) & SOC', 'Placebo & SOC']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Paris', 'country': 'France', 'facility': "Institut de la mémoire et Maladie d'Alzheimer, Hôpitaux Universitaires Pitié-Salpêtrière", 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}, {'city': 'Albacete', 'country': 'Spain', 'facility': 'Hospital Universitario Nuestra Señora del Perpetuo Socorro de Albacete (Hospital Universitario Nuestra Señora del Perpétuo Socorro)', 'geoPoint': {'lat': 38.99424, 'lon': -1.85643}}, {'city': 'Barcelona', 'country': 'Spain', 'facility': 'Ace Alzheimer Center Barcelona (Fundació ACE)', 'geoPoint': {'lat': 41.38879, 'lon': 2.15899}}, {'city': 'Donostia / San Sebastian', 'country': 'Spain', 'facility': 'Hospital Policlínico de Gipuzkoa', 'geoPoint': {'lat': 43.31283, 'lon': -1.97499}}, {'city': 'Granada', 'country': 'Spain', 'facility': 'Virgen de las Nieves University Hospital (Hospital Universitario Virgen de las Nieves)', 'geoPoint': {'lat': 37.18817, 'lon': -3.60667}}, {'city': 'Madrid', 'country': 'Spain', 'facility': 'La Paz University Hospital (Hospital Universitario La Paz)', 'geoPoint': {'lat': 40.4165, 'lon': -3.70256}}, {'city': 'Murcia', 'country': 'Spain', 'facility': 'Hospital Clinico Universitario Virgen de la Arrixaca', 'geoPoint': {'lat': 37.98704, 'lon': -1.13004}}, {'city': 'Pamplona', 'country': 'Spain', 'facility': 'Hospital Universitario de Navarra', 'geoPoint': {'lat': 42.81687, 'lon': -1.64323}}, {'city': 'Zamora', 'country': 'Spain', 'facility': 'Complejo Asistencial de Zamora. Hospital Provincial de Zamora', 'geoPoint': {'lat': 41.50633, 'lon': -5.74456}}], 'centralContacts': [{'name': 'Clinical Study Coordinator', 'role': 'CONTACT', 'email': 'clinical@ab-science.com', 'phone': '+33(0)147200014'}], 'overallOfficials': [{'name': 'Bruno Dubois, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Hôpital Universitaire Pitié-Salpêtrière, Paris, France'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'AB Science', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}