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

Purpose

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).

Condition

  • Amyotrophic Lateral Sclerosis

Eligibility

Eligible Ages
Between 18 Years and 81 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Masitinib (4.5) & Riluzole 		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
  • Drug: Riluzole
    Riluzole 50 mg tablet, treatment per os
    Other names:
    • Rilutek
  • Drug: Masitinib (4.5)
    Masitinib (titration to 4.5 mg/kg/day)
    Other names:
    • AB1010
Experimental
Masitinib (6.0) & Riluzole 		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.
  • Drug: Masitinib (6.0)
    Masitinib (titration to 6.0 mg/kg/day)
    Other names:
    • AB1010
  • Drug: Riluzole
    Riluzole 50 mg tablet, treatment per os
    Other names:
    • Rilutek
Placebo Comparator
Placebo & Riluzole 		Participants receive a matched dose placebo, given orally twice daily, in combination with riluzole at 50 mg b.i.d.
  • Drug: Riluzole
    Riluzole 50 mg tablet, treatment per os
    Other names:
    • Rilutek
  • Drug: Placebo
    treatment per os
    Other names:
    • Placebo Oral Tablet

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35294

More Details

Status
Recruiting
Sponsor
AB Science

Study Contact

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

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).