Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
- 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
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Masitinib (4.5) & Riluzole Masitinib (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 & Riluzole Placebo Participants receive a matched dose placebo, given orally twice daily, in combination with riluzole at 50 mg b.i.d. Masitinib (6.0) & Riluzole Masitinib (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) & Riluzole 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 Masitinib (6.0) & Riluzole 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. Placebo & Riluzole Riluzole Participants receive a matched dose placebo, given orally twice daily, in combination with riluzole at 50 mg b.i.d.
- Primary Outcome Measures
Name Time Method ALSFRS-R 48 weeks Change in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised.
- Secondary Outcome Measures
Name Time Method ALSAQ-40 48 weeks Change in ALS quality of life patient questionnaire (ALSAQ-40)
PFS From 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
FVC 48 weeks Change in Forced Vital Capacity (FVC)
HHD 48 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 48 48 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
Scroll for more (46 remaining)University of Alabama at Birmingham🇺🇸Birmingham, Alabama, United States