Clinical Trials List
Protocol NumberAB09004
2013-05-20 - 2018-12-31
Phase III
Terminated6
ICD-10G30.0
Alzheimer's disease with early onset
ICD-10G30.1
Alzheimer's disease with late onset
ICD-10G30.8
Other Alzheimer's disease
ICD-10G30.9
Alzheimer's disease, unspecified
ICD-9331.0
Alzheimer's disease
A multicenter, double-blind, placebo-controlled, randomised, parallel-group phase 3 study to evaluate the safety and efficacy of masitinib in patients with mild to moderate Alzheimer’s disease.
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Trial Applicant
ClinActis Pte Ltd
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Sponsor
AB Science
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- KuoLun Huang Division of Neurology
- Chi-Hung Liu Division of Neurology
- Hong-Chou Kuo Division of Neurology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 洪偉斌 Division of Neurology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Wei-Shih Huang Division of Neurology
- Yuh-Cherng Guo Division of Neurology
- Ming-Kuei Lu Division of Neurology
- Kang-Hsu Lin Division of Neurology
- Chung-Hsiang Liu Division of Neurology
- Hui-Chun Huang Division of Neurology
- Chon-Haw Tsai Division of Neurology
- Yi-Ting Hsu Division of Neurology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chia-Fen Tsai Division of Neurology
- Shuu-Jiun Wang Division of Neurology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- MEI-CHUAN CHOU Division of Neurology
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
mild to moderate Alzheimer’s disease
Objectives
The objective is to compare the efficacy and safety of oral masitinib 3 or 4.5 mg/kg/day in combination with cholinesterase inhibitors and/or memantine to placebo in combination with cholinesterase inhibitors and/or memantine in patients with mild-to-moderate Alzheimer’s disease.
During this clinical trial, ancillary studies will be performed:
- a pharmacogenomic study in order to define efficacy or safety genomic predictive criteria.
- a MRI study to define a new precoce marker of Alzheimer‘s disease
Test Drug
masitinib
Active Ingredient
masitinib
Dosage Form
tablet
Dosage
100 and 200 mg matching Placebo
Endpoints
Assessment criteria
1. Efficacy:
- Effect on cognition and memory assessed by Alzheimer’s disease Assessment Scale (ADAS-Cog) at Week 24.
- Effect on self-care and activities of daily living assessed by Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL) at Week 24.
2. Safety:
Occurrence of Adverse Events (AE), changes on clinical examination including vital signs (blood pressure, pulse rate) and weight, ECG and laboratory exams (biochemistry, hematology and urinalysis)
3. Pharmacokinetics: Not Applicable.
4. Quality of life:
- ADAS-Cog at Week 8 and Week 12
- ADAS-Cog response and worsening rates at Week 8, Week 12 and Week 24
- ADCS-ADL at Week 8 and Week 12
- ADCS-ADL response and worsening rate at Week 8, Week 12 and Week 24
- Clinician’s Interview Based Impression of Change-plus (CIBIC-plus) at Week 8, Week 12 and Week 24
- Mini-Mental State Examination (MMSE) at Week 8, Week 12 and Week 24
- Neuropsychiatric Inventory (NPI) at Week 12 and Week 24
- Clinical Dementia Rating (CDR) at Week 12 and Week 24
- Clinical responder rate at Week 8, Week 12 and Week 24
5. Others:
- Pharmacogenomic assessment: relationship between genomic data, efficacy variables (ADAS-Cog and ADCS-ADL) and safety
- MRI assessment at Week 24
1. Efficacy:
- Effect on cognition and memory assessed by Alzheimer’s disease Assessment Scale (ADAS-Cog) at Week 24.
- Effect on self-care and activities of daily living assessed by Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL) at Week 24.
2. Safety:
Occurrence of Adverse Events (AE), changes on clinical examination including vital signs (blood pressure, pulse rate) and weight, ECG and laboratory exams (biochemistry, hematology and urinalysis)
3. Pharmacokinetics: Not Applicable.
4. Quality of life:
- ADAS-Cog at Week 8 and Week 12
- ADAS-Cog response and worsening rates at Week 8, Week 12 and Week 24
- ADCS-ADL at Week 8 and Week 12
- ADCS-ADL response and worsening rate at Week 8, Week 12 and Week 24
- Clinician’s Interview Based Impression of Change-plus (CIBIC-plus) at Week 8, Week 12 and Week 24
- Mini-Mental State Examination (MMSE) at Week 8, Week 12 and Week 24
- Neuropsychiatric Inventory (NPI) at Week 12 and Week 24
- Clinical Dementia Rating (CDR) at Week 12 and Week 24
- Clinical responder rate at Week 8, Week 12 and Week 24
5. Others:
- Pharmacogenomic assessment: relationship between genomic data, efficacy variables (ADAS-Cog and ADCS-ADL) and safety
- MRI assessment at Week 24
Inclution Criteria
1. Main inclusion criteria:
1) Male or female patient
2) Age ≥ 50 years, weighing more than ≥ 49,9 kg and with a Body Mass Index (BMI) >18 at screening
3) Patient and/ or caregiver able to understand the patient card and to follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity, during the first 2 months of treatment
4) Menopause ≥ 2 years for female patient
5) Patient with dementia of Alzheimer's type, according to DSM-IV criteria
6) Patient with probable Alzheimer' disease according to NINCDS-ADRDA criteria
7) Patient with MMSE ≥ 12 and ≤ 25 at baseline
8) Patient treated for a minimum of 6 months with a stable dose of cholinesterase inhibitors (donepezil, rivastigmine or galantamine) at baseline, and/or a stable dose of memantine for a minimum of 6 months at baseline, with no changes foreseen in therapy throughout the study
9) Patient with adequate organ function at screening and baseline:
• Absolute Neutrophils Count (ANC) ≥ 2 x 109/L
• Hemoglobin ≥ 10 g/dL
• Platelets (PTL) ≥ 100 x 109/L
• AST/ALT ≤ 2.5 ULN
• Bilirubin ≤ 1.5 ULN
• Albuminemia > 1 x LLN
• Urea ≤ 1.5 x ULN
• Creatinine clearance > 60 mL/min (Cockcroft and Gault formula)
• Proteinuria < 30 mg/dL on dipstick; in case of the proteinuria ≥ 30 mg/dL, 24 hours proteinuria < 1.5g/24 hours
10) Patient with a regular and reliable caregiver. The designated caregiver must be sufficiently familiar with the patient (as determined by the investigator) to provide accurate data. The caregiver must have regular contact with the patient (i.e., an average of 10 or more hours per week), must be able to observe for possible adverse events, must be able to oversee patient’s compliance with the study treatment and to report on the patient’s status and must be able to accompany the patient to all visits
11) Patient, identified caregiver and, if applicable, patient surrogate able and willing to comply with study visits and procedures per protocol, understand, sign, and date the informed consent form at screening visit prior to any protocol-specific procedures performed
12) Male patient must agree to use one method of medically acceptable forms of contraception (his partner must also use one if she is of child-bearing potential) during the study and for 3 months after the last treatment intake.
1) Male or female patient
2) Age ≥ 50 years, weighing more than ≥ 49,9 kg and with a Body Mass Index (BMI) >18 at screening
3) Patient and/ or caregiver able to understand the patient card and to follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity, during the first 2 months of treatment
4) Menopause ≥ 2 years for female patient
5) Patient with dementia of Alzheimer's type, according to DSM-IV criteria
6) Patient with probable Alzheimer' disease according to NINCDS-ADRDA criteria
7) Patient with MMSE ≥ 12 and ≤ 25 at baseline
8) Patient treated for a minimum of 6 months with a stable dose of cholinesterase inhibitors (donepezil, rivastigmine or galantamine) at baseline, and/or a stable dose of memantine for a minimum of 6 months at baseline, with no changes foreseen in therapy throughout the study
9) Patient with adequate organ function at screening and baseline:
• Absolute Neutrophils Count (ANC) ≥ 2 x 109/L
• Hemoglobin ≥ 10 g/dL
• Platelets (PTL) ≥ 100 x 109/L
• AST/ALT ≤ 2.5 ULN
• Bilirubin ≤ 1.5 ULN
• Albuminemia > 1 x LLN
• Urea ≤ 1.5 x ULN
• Creatinine clearance > 60 mL/min (Cockcroft and Gault formula)
• Proteinuria < 30 mg/dL on dipstick; in case of the proteinuria ≥ 30 mg/dL, 24 hours proteinuria < 1.5g/24 hours
10) Patient with a regular and reliable caregiver. The designated caregiver must be sufficiently familiar with the patient (as determined by the investigator) to provide accurate data. The caregiver must have regular contact with the patient (i.e., an average of 10 or more hours per week), must be able to observe for possible adverse events, must be able to oversee patient’s compliance with the study treatment and to report on the patient’s status and must be able to accompany the patient to all visits
11) Patient, identified caregiver and, if applicable, patient surrogate able and willing to comply with study visits and procedures per protocol, understand, sign, and date the informed consent form at screening visit prior to any protocol-specific procedures performed
12) Male patient must agree to use one method of medically acceptable forms of contraception (his partner must also use one if she is of child-bearing potential) during the study and for 3 months after the last treatment intake.
Exclusion Criteria
Selection criteria
1. Main inclusion criteria:
1) Male or female patient
2) Age ≥ 50 years, weighing more than ≥ 49,9 kg and with a Body Mass Index (BMI) >18 at screening
3) Patient and/ or caregiver able to understand the patient card and to follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity, during the first 2 months of treatment
4) Menopause ≥ 2 years for female patient
5) Patient with dementia of Alzheimer's type, according to DSM-IV criteria
6) Patient with probable Alzheimer' disease according to NINCDS-ADRDA criteria
7) Patient with MMSE ≥ 12 and ≤ 25 at baseline
8) Patient treated for a minimum of 6 months with a stable dose of cholinesterase inhibitors (donepezil, rivastigmine or galantamine) at baseline, and/or a stable dose of memantine for a minimum of 6 months at baseline, with no changes foreseen in therapy throughout the study
9) Patient with adequate organ function at screening and baseline:
• Absolute Neutrophils Count (ANC) ≥ 2 x 109/L
• Hemoglobin ≥ 10 g/dL
• Platelets (PTL) ≥ 100 x 109/L
• AST/ALT ≤ 2.5 ULN
• Bilirubin ≤ 1.5 ULN
• Albuminemia > 1 x LLN
• Urea ≤ 1.5 x ULN
• Creatinine clearance > 60 mL/min (Cockcroft and Gault formula)
• Proteinuria < 30 mg/dL on dipstick; in case of the proteinuria ≥ 30 mg/dL, 24 hours proteinuria < 1.5g/24 hours
10) Patient with a regular and reliable caregiver. The designated caregiver must be sufficiently familiar with the patient (as determined by the investigator) to provide accurate data. The caregiver must have regular contact with the patient (i.e., an average of 10 or more hours per week), must be able to observe for possible adverse events, must be able to oversee patient’s compliance with the study treatment and to report on the patient’s status and must be able to accompany the patient to all visits
11) Patient, identified caregiver and, if applicable, patient surrogate able and willing to comply with study visits and procedures per protocol, understand, sign, and date the informed consent form at screening visit prior to any protocol-specific procedures performed
12) Male patient must agree to use one method of medically acceptable forms of contraception (his partner must also use one if she is of child-bearing potential) during the study and for 3 months after the last treatment intake.
2. Main exclusion criteria:
1) Patient with any other cause of dementia not due to Alzheimer's disease, based on specific examination including a brain neuro-imagery exam within the last 6 months:
• Other central nervous condition causing progressive deficits in memory and cognition, e.g. cerebrovascular disease (patient with not more than 4 microbleeds and not more than 2 lacunes at the MRI could be enrolled in the study), Parkinson's disease, Huntington's disease, brain tumor…
• Systemic conditions known to cause dementia, e.g., hypothyroidism, untreated vitamin B12 or folic acid deficiency, niacin deficiency, neurosyphilis, HIV infection…
• Substance-induced dementia
2) Patient with Alzheimer disease with severe forms of delusions or delirium (patients with light and mild forms of delusions and delirium will be allowed in the study)
3) Patient treated with any registered or putative cognitive/memory enhancer or disease modifier other than donepezil, galantamine, rivastigmine or memantine. (Patient taking Ginkgo Biloba can be enrolled providing it has been taken at a stable dose for at least 6 months).
4) Patient with evidence of psychosis and/or use of antipsychotic drugs at screening, or history of significant psychiatric disorder
5) Patient with active current bacterial, viral (including hepatitis B and C, HIV, EBV, CMV, herpes zoster), fungal, mycobacterium, protozoan, or other infection
6) Patient with history of infection requiring hospitalization within 2 weeks of screening
7) Patient presenting with cardiac disorders defined by at least one of the following conditions:
• Patient with recent cardiac history (within 6 months) of:
- Acute coronary syndrome
- Acute heart failure (class III or IV of the NYHA classification)
- Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
• Patient with cardiac failure class III or IV of the NYHA classification
• Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
• Syncope without known aetiology within 3 months
• Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension
8) Patient with chronic diarrhea
9) Patient presenting with oedemas
10) Patient with co existing dermatological disease (e.g. eczema, psoriasis) or history of skin allergy
11) Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent
12) Patient with life expectancy < 1 year
Previous medications:
13) Patient treated with any investigational agent within 4 weeks of screening
1. Main inclusion criteria:
1) Male or female patient
2) Age ≥ 50 years, weighing more than ≥ 49,9 kg and with a Body Mass Index (BMI) >18 at screening
3) Patient and/ or caregiver able to understand the patient card and to follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity, during the first 2 months of treatment
4) Menopause ≥ 2 years for female patient
5) Patient with dementia of Alzheimer's type, according to DSM-IV criteria
6) Patient with probable Alzheimer' disease according to NINCDS-ADRDA criteria
7) Patient with MMSE ≥ 12 and ≤ 25 at baseline
8) Patient treated for a minimum of 6 months with a stable dose of cholinesterase inhibitors (donepezil, rivastigmine or galantamine) at baseline, and/or a stable dose of memantine for a minimum of 6 months at baseline, with no changes foreseen in therapy throughout the study
9) Patient with adequate organ function at screening and baseline:
• Absolute Neutrophils Count (ANC) ≥ 2 x 109/L
• Hemoglobin ≥ 10 g/dL
• Platelets (PTL) ≥ 100 x 109/L
• AST/ALT ≤ 2.5 ULN
• Bilirubin ≤ 1.5 ULN
• Albuminemia > 1 x LLN
• Urea ≤ 1.5 x ULN
• Creatinine clearance > 60 mL/min (Cockcroft and Gault formula)
• Proteinuria < 30 mg/dL on dipstick; in case of the proteinuria ≥ 30 mg/dL, 24 hours proteinuria < 1.5g/24 hours
10) Patient with a regular and reliable caregiver. The designated caregiver must be sufficiently familiar with the patient (as determined by the investigator) to provide accurate data. The caregiver must have regular contact with the patient (i.e., an average of 10 or more hours per week), must be able to observe for possible adverse events, must be able to oversee patient’s compliance with the study treatment and to report on the patient’s status and must be able to accompany the patient to all visits
11) Patient, identified caregiver and, if applicable, patient surrogate able and willing to comply with study visits and procedures per protocol, understand, sign, and date the informed consent form at screening visit prior to any protocol-specific procedures performed
12) Male patient must agree to use one method of medically acceptable forms of contraception (his partner must also use one if she is of child-bearing potential) during the study and for 3 months after the last treatment intake.
2. Main exclusion criteria:
1) Patient with any other cause of dementia not due to Alzheimer's disease, based on specific examination including a brain neuro-imagery exam within the last 6 months:
• Other central nervous condition causing progressive deficits in memory and cognition, e.g. cerebrovascular disease (patient with not more than 4 microbleeds and not more than 2 lacunes at the MRI could be enrolled in the study), Parkinson's disease, Huntington's disease, brain tumor…
• Systemic conditions known to cause dementia, e.g., hypothyroidism, untreated vitamin B12 or folic acid deficiency, niacin deficiency, neurosyphilis, HIV infection…
• Substance-induced dementia
2) Patient with Alzheimer disease with severe forms of delusions or delirium (patients with light and mild forms of delusions and delirium will be allowed in the study)
3) Patient treated with any registered or putative cognitive/memory enhancer or disease modifier other than donepezil, galantamine, rivastigmine or memantine. (Patient taking Ginkgo Biloba can be enrolled providing it has been taken at a stable dose for at least 6 months).
4) Patient with evidence of psychosis and/or use of antipsychotic drugs at screening, or history of significant psychiatric disorder
5) Patient with active current bacterial, viral (including hepatitis B and C, HIV, EBV, CMV, herpes zoster), fungal, mycobacterium, protozoan, or other infection
6) Patient with history of infection requiring hospitalization within 2 weeks of screening
7) Patient presenting with cardiac disorders defined by at least one of the following conditions:
• Patient with recent cardiac history (within 6 months) of:
- Acute coronary syndrome
- Acute heart failure (class III or IV of the NYHA classification)
- Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
• Patient with cardiac failure class III or IV of the NYHA classification
• Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
• Syncope without known aetiology within 3 months
• Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension
8) Patient with chronic diarrhea
9) Patient presenting with oedemas
10) Patient with co existing dermatological disease (e.g. eczema, psoriasis) or history of skin allergy
11) Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent
12) Patient with life expectancy < 1 year
Previous medications:
13) Patient treated with any investigational agent within 4 weeks of screening
The Estimated Number of Participants
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Taiwan
40 participants
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Global
396 participants
