Amyotrophic Lateral Sclerosis
Conditions
Keywords
Amyotrophic Lateral Sclerosis, ALS, Tyrosine kinase inhibitor, Lou Gehrig's disease, Charcot's disease, Motor Neuron disease, MND
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).
Interventions
DRUGMasitinib (6.0)
Masitinib (titration to 6.0 mg/kg/day)
DRUGRiluzole
Riluzole 50 mg tablet, treatment per os
DRUGPlacebo
treatment per os
DRUGMasitinib (4.5)
Masitinib (titration to 4.5 mg/kg/day)
Sponsors
AB Science
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 81 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ALSFRS-R | 48 weeks | Change in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Belgium, Denmark, France, Germany, Greece, Israel, Italy, Norway, Poland, Portugal, Russia, Serbia, Slovenia, Spain, Sweden, Ukraine, United States
Contacts
Primary ContactClinical Study Coordinator
Outcome results
None listed