Masitinib in Combination With Riluzole for the Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis (ALS)

Study Overview
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Brief Summary
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The objective is to compare the efficacy and safety of masitinib in combination with riluzole in the treatment of patients suffering from Amyotrophic Lateral Sclerosis (ALS).

Detailed Description
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Masitinib is novel tyrosine kinase inhibitor that targets microglia and mast cells through inhibiting a limited number of kinases. Masitinib blocks microglia proliferation and activation, and mast cell-mediated degranulation, the release of cytotoxic substances that might further damage the motor nerves. There are two distinct populations of ALS patients: population of Normal progressors and population of Faster progressors. Targeted population for primary analysis is population of Normal progressors. Normal progressors are ALS patients whose progression of ALSFRS-R score before randomization is less than 1.1 point per month.

Official Title
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Multicenter, Randomised, Double-blind, Placebo-controlled, Parallel Group, Phase 2/3 Study to Compare the Efficacy and Safety of Masitinib

Conditions
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Amyotrophic Lateral Sclerosis (ALS)

Intervention / Treatment
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* Drug: Masitinib (4.5)
* Drug: Riluzole
* Drug: Placebo
* Drug: Masitinib (3.0)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Main inclusion criteria: Familial or sporadic ALS Patient diagnosed with probable of definite ALS Patient treated with a stable dose of riluzole (100 mg/day) for at least 30 days prior to screening Exclusion Criteria: 1. Patient who underwent tracheostomy and/or gastrostomy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Masitinib (3.0) & Riluzole<br>masitinib 3 mg/kg/day + riluzole | Drug: Riluzole<br> <br> * Other names: Rilutek;Drug: Masitinib (3.0)<br>* 3 mg/kg/day<br>* Other names: AB1010;|
| Experimental: Masitinib (4.5) & Riluzole<br>masitinib 4.5 mg/kg/day (2) + riluzole | Drug: Masitinib (4.5)<br>* 4.5 mg/kg/day<br>* Other names: AB1010;Drug: Riluzole<br> <br> * Other names: Rilutek;|
| Placebo Comparator: Placebo & Riluzole<br>Matched placebo | Drug: Riluzole<br> <br> * Other names: Rilutek;Drug: Placebo<br> <br> * Other names: Placebo Oral Tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised | The amyotrophic lateral sclerosis functional rating scale (ALSFRS), which is a Validated instrument that assesses the functional status and the disease progression in patients with amyotrophic lateral sclerosis (ALS) | From baseline to week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Forced Vital Capacity (FVC) | Forced vital capacity (FVC) measures the volume of air expelled from the lungs during a quick, forceful breath. | From baseline to week 48 | 
| Progression Free Survival | Progression Free Survival is defined as the time from the randomization date until the earliest date for a decline of more than 9-points in ALSFRS-R score | Time from the randomization date until the earliest date for a decline of more than 9-points in ALSFRS-R score, asssesd over a maximum of 60 months | 
| Overall Survival | Overall survival is defined as time in months from the randomization date to the date of death due to any cause. | Time from the randomization date until death, asssesd over a maximum of 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amyotrophic Lateral Sclerosis (ALS) - masitinib