A Phase 3 Study to Evaluate the Safety and Efficacy of Masitinib in Patients With Mild to Moderate Alzheimer's Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by AB Science
Sponsor:
Information provided by (Responsible Party):
AB Science
ClinicalTrials.gov Identifier:
NCT01872598
First received: June 5, 2013
Last updated: June 6, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Alzheimer Disease
Drug: Group 1
Drug: Group 2
Drug: Group 3
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AB Science:

Primary Outcome Measures:
  • Cognition and Memory assessment [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Effect on cognition and memory assessed by Alzheimer's disease Assessment Scale (ADAS-Cog)

  • Self-care and daily activities assesment [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Effect on self-care and activities of daily living assessed by Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL)


Estimated Enrollment: 396
Study Start Date: January 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Masitinib 3mg/kg/day
Drug: Group 1
Other Name: Masitinib 3 mg/kg/day
Experimental: Group 2
Masitinib 4.5mg/kg/day
Drug: Group 2
Other Name: Masitinib 4.5 mg/kg/day
Placebo Comparator: Group 3
Placebo 3 mg or 4.5mg/kg/day
Drug: Group 3
Other Name: Placebo 3 or 4.5 mg/kg/day

Detailed Description:

Actual standard treatment for mild to moderately severe Alzheimer's dementia includes acetylcholinesterase inhibitors (donepezil, rivastigmine and galantamine) and a NMDA receptor antagonist (memantine for moderate to severe Alzheimer's disease). These medications have shown to have an effect on some cognitive and non cognitive symptoms of the pathology. However, their efficacy remains limited and may decrease with time. There is an unmet medical need in this pathology. Based on pre-clinical and clinical studies, masitinib (AB1010) can be considered as a good candidate at the dose of 3 and 4.5 mg/kg/day.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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
  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. MMSE ≥ 12 and ≤ 25 at baseline
  8. Patient treated for a minimum of 6 months with a stable dose of cholinesterase inhibitors (rivastigmine) 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
    • Creatinin clearance > 60 mL/min (Cockcroft and Gault formula)
    • Proteinuria < 30 mg/dL on dipstick; in case of the proteinuria ≥ 30mg/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 the 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:

  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 rivastigmine or memantine. (Patients 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01872598

Contacts
Contact: Bruno DUBOIS, M.D., Ph.D. bruno.dubois@psl.aphp.fr

Locations
Spain
Hospital Universitario Ramón y Cajal Recruiting
Madrid, Spain, 28034
Principal Investigator: Alfonso CRUZ, MD         
Sponsors and Collaborators
AB Science
Investigators
Principal Investigator: Bruno DUBOIS, M.D., Ph.D. Pitié-Salpétrière
  More Information

No publications provided

Responsible Party: AB Science
ClinicalTrials.gov Identifier: NCT01872598     History of Changes
Other Study ID Numbers: AB09004
Study First Received: June 5, 2013
Last Updated: June 6, 2013
Health Authority: Spain: Spanish Agency of Medicines
Greece: National Organization of Medicines
Poland: Ministry of Health
Romania: National Authority for Scientific Research
Singapore: Ministry of Health
Slovakia: State Institute for Drug Control
United States: Food and Drug Administration

Keywords provided by AB Science:
Alzheimer
dementia
cognitive disease
memory loss
cerebrovascular disease

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on September 18, 2014