Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients

Phase 3RecruitingNCT03127267

AB Science495 enrolled

Overview

The objective is to compare the efficacy and safety of masitinib in combination with riluzole versus matched placebo in combination with riluzole for the treatment of Amyotrophic Lateral Sclerosis (ALS).

Masitinib is a selective, oral tyrosine kinase inhibitor with neuroprotective capability demonstrated via numerous preclinical studies. Two of masitinib's main cellular targets are the mast cell and microglia cell. It is well-established that mast cells play a prominent role in neuroinflammatory processes. Microglia, resident immune cells of the central nervous system (CNS), also constitute an important source of neuroinflammatory mediators and may have fundamental roles in numerous neurodegenerative disorders. The development of masitinib in ALS is therefore based on the pharmacological action of masitinib in microglia cells and mast cells, thereby slowing microglial-related disease progression, reducing neuro-inflammation, and modulating the neuronal microenvironment in both central and peripheral nervous systems. This is a multicenter, double-blind, randomized, placebo-controlled, parallel-group (two ascending dose titrations of masitinib and matching placebo), comparative study of oral masitinib in the treatment of patients with amyotrophic lateral sclerosis (ALS).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

495

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Masitinib (6.0)DRUG

Masitinib (titration to 6.0 mg/kg/day)

RiluzoleDRUG

Riluzole 50 mg tablet, treatment per os

PlaceboDRUG

treatment per os

Masitinib (4.5)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 81 Years

Medical Language ↔ Plain English

Main inclusion criteria include: * Patients diagnosed with laboratory supported probable, clinically probable or definite ALS according to the World Federation of Neurology Revised El Escorial criteria * Patient with a familial or sporadic ALS * ALS disease duration from diagnosis no longer than 24 months at the screening visit * Patient treated with a stable dose of riluzole (100 mg/day) for at least 12 weeks days prior to the baseline visit * Patient with an ALSFRS-R score progression between onset of the disease and screening of \> 0.3 per month, confirmed with an ALSFRS-R score progression of ≥ 1 point during a 12-week run-in period between screening and randomization. * Patient with a score, at screening, of at least 26 overall, including a score of at least 3 on item #3 and at least 2 on each of the 12 ALSFRS-R individual component items and with a score, at randomization, of at least 2 on each of the 12 ALSFRS-R individual component items Main exclusion criteria include: * Patient with dementia or significant neurological, psychiatric, systemic or organic disease, uncontrolled or that may interfere with the conduct of the trial or its results * Patient with a FVC \< 60% predicted normal value for gender, height, and age at screening and baseline * Pregnant, or nursing female patient

Locations (56)

Outcomes

Primary Outcomes

ALSFRS-R

Change in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised.

Time frame: 48 weeks

Secondary Outcomes

ALSAQ-40

Change in ALS quality of life patient questionnaire (ALSAQ-40)

Time frame: 48 weeks

PFS

Progression free survival (PFS) is defined as the time from randomization to progression (decline of more than 9 points in ALSFRS-R score from baseline) or death

Time frame: From day of randomization to disease progression or death, assessed for a maximum of 36 months

FVC

Change in Forced Vital Capacity (FVC)

Time frame: 48 weeks

HHD

Change in evaluation of upper- and lower-limb muscle strength using hand-held dynamometry (HHD)

Time frame: 48 weeks

Change in the Combined Assessment of Function and Survival (CAFS) score from baseline to week 48

CAFS ranks patients' clinical outcomes based on survival time and change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score. Each patient's outcome is compared to every other patient's outcome, assigned a score, and the summed scores are ranked. The mean rank score for each treatment group can then be calculated. A higher mean CAFS score indicates a better group outcome.

Time frame: 48 weeks

Central Contacts

Clinical Study Coordinator

CONTACT

+33(0)147200014 clinical@ab-science.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

University of Alabama at Birmingham

Birmingham, Alabama, United States

RECRUITING

University of Southern California

Los Angeles, California, United States

RECRUITING

University of Kentucky

Lexington, Kentucky, United States

RECRUITING

Johns Hopkins Medicine Brain Science Institute

Baltimore, Maryland, United States

RECRUITING

Lahey Hospital and Medical Center

Burlington, Massachusetts, United States

RECRUITING

University of Virginia Health System

Charlottesville, Virginia, United States

RECRUITING

University Hospital Leuven (UZ Leuven)

Leuven, Belgium

RECRUITING

Bispebjerg Hospital

Copenhagen, Denmark

RECRUITING

CHU de Angers

Angers, France

RECRUITING

Groupe Hospitalier Pellegrin Tripode

Bordeaux, France

RECRUITING

...and 46 more locations