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

Phase 3
Recruiting
Conditions
Amyotrophic Lateral Sclerosis
Interventions
Registration Number
NCT03127267
Lead Sponsor
AB Science
Brief Summary

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).

Detailed Description

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).

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
495
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Masitinib (4.5) & RiluzoleMasitinib (4.5)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. Each ascending dose titration is subjected to a safety control. Masitinib will be administered as an add-on to riluzole at 50 mg b.i.d
Placebo & RiluzolePlaceboParticipants receive a matched dose placebo, given orally twice daily, in combination with riluzole at 50 mg b.i.d.
Masitinib (6.0) & RiluzoleMasitinib (6.0)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, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control. Masitinib will be administered as an add-on to riluzole at 50 mg b.i.d.
Masitinib (4.5) & RiluzoleRiluzoleParticipants 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. Each ascending dose titration is subjected to a safety control. Masitinib will be administered as an add-on to riluzole at 50 mg b.i.d
Masitinib (6.0) & RiluzoleRiluzoleParticipants 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, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control. Masitinib will be administered as an add-on to riluzole at 50 mg b.i.d.
Placebo & RiluzoleRiluzoleParticipants receive a matched dose placebo, given orally twice daily, in combination with riluzole at 50 mg b.i.d.
Primary Outcome Measures
NameTimeMethod
ALSFRS-R48 weeks

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

Secondary Outcome Measures
NameTimeMethod
ALSAQ-4048 weeks

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

PFSFrom day of randomization to disease progression or death, assessed for a maximum of 36 months

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

FVC48 weeks

Change in Forced Vital Capacity (FVC)

HHD48 weeks

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

Change in the Combined Assessment of Function and Survival (CAFS) score from baseline to week 4848 weeks

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.

Trial Locations

Locations (56)

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

University of Southern California

🇺🇸

Los Angeles, California, United States

University of Kentucky

🇺🇸

Lexington, Kentucky, United States

Johns Hopkins Medicine Brain Science Institute

🇺🇸

Baltimore, Maryland, United States

Lahey Hospital and Medical Center

🇺🇸

Burlington, Massachusetts, United States

University of Virginia Health System

🇺🇸

Charlottesville, Virginia, United States

University Hospital Leuven (UZ Leuven)

🇧🇪

Leuven, Belgium

Bispebjerg Hospital

🇩🇰

Copenhagen, Denmark

CHU de Angers

🇫🇷

Angers, France

Groupe Hospitalier Pellegrin Tripode

🇫🇷

Bordeaux, France

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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States

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