Activity of Masitinib (AB1010) in Mild to Moderate Alzheimer's Disease

A Multicenter, Double-blind, Placebo-controlled, Randomized, Parallel-group Study to Evaluate the Efficacy of Oral AB1010 in Adults Patients With Mild to Moderate Alzheimer-type Disease.

This phase 2 study was designed to evaluate the activity of oral masitinib (AB1010) administered at 2 dose levels during 24 weeks to patients with mild to moderate confirmed Alzheimer's type disease.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: placebo; Drug: masitinib (AB1010)

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Outpatients from both sex
2. Age ≥ 50 years at screening
3. Menopause ≥ 2 years for women
4. Dementia of Alzheimer's type, according to DSM IV criteria
5. Probable Alzheimer' disease according to NINCDS-ADRDA criteria
6. MMSE ≥ 12 and ≤ 26 at baseline
7. CDR of 1 or 2 at baseline
8. 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 3 months at baseline, with no changes foreseen in therapy throughout the study
9. Presence of a reliable caregiver
10. Patient, identified caregiver and, if applicable, patient surrogate are able and willing to comply with study visits and procedures per protocol, understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed
11. Affiliated to the French Social Security regimen

Exclusion Criteria:

1. Any cause of dementia not due to Alzheimer's disease :

   • other central nervous conditions causing progressive deficits in memory and cognition, e.g. cerebrovascular disease, 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 conditions
2. Alzheimer disease with delusions or delirium
3. Treatment with any registered or putative cognitive enhancer or disease modifier other than donepezil, galantamine, rivastigmine or memantine
4. Uncontrolled depression at screening
5. Evidence of psychosis and/or use of antipsychotic drugs at screening, or history of significant psychotic disorder or hospitalization for psychiatric disorders
6. Active current bacterial, viral (including hepatitis B and C, HIV, EBV, CMV, herpes zoster, herpes simplex), fungal, mycobacterium, protozoan, or other infection.
7. History of infection requiring hospitalization or treatment with antibiotics within 2 weeks of screening
8. Inadequate organ function, defined as follows : total bilirubin ≥ 1.5 x ULN, SGOT and SGPT ≥ 2.5 x UNL, creatinine clearance calculated by Crocroft method < 35 ml/mn, ANC ≤ 2500, platelets ≤ 100 000 at baseline
9. Treatment with any investigational agent within 4 weeks of screening,
10. Men and their partner refusing to use 2 methods of medically acceptable forms of contraception during the study.
11. 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. Any condition that, in the investigator's opinion, could be detrimental to subjects participating in this study as life expectancy < 1 year, or any clinically important deviations from normal clinical laboratory values or concurrent medical events.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: placebo; matching placebo to masitinib
Experimental: oral masitinib (AB1010); masitinib (AB1010) 3 or 6 mg/kg/day	Drug: masitinib (AB1010); oral masitinib 3 or 6 mg/kg/day; Other Names: AB1010

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
change from baseline in ADAS-Cog	week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
change from baseline in CIBIC-plus	week 24
change from baseline in CDR	week 24
change from baseline in MMSE	week 24

Collaborators and Investigators

• Sponsor: AB Science

Publications and helpful links

General 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.

Helpful Links

• Publication of results

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: September 11, 2009
• First Submitted That Met QC Criteria: September 11, 2009
• First Posted (Estimate): September 14, 2009

Study Record Updates

• Last Update Posted (Actual): December 13, 2018
• Last Update Submitted That Met QC Criteria: December 12, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: mild to moderate Alzheimer's Disease; Dementia of Alzheimer's type
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: AB04024

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No