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

AB Science

Status and phase: Enrolling; Phase 3

Conditions: Amyotrophic Lateral Sclerosis

Treatments: Drug: Placebo; Drug: Masitinib (4.5); Drug: Riluzole; Drug: Masitinib (6.0)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03127267

AB19001

Details and patient eligibility

About

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).

Full 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).

Enrollment: 495 estimated patients

Sex: All

Ages: 18 to 81 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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495 participants in 3 patient groups, including a placebo group

Masitinib (4.5) & Riluzole

Experimental group

Description:

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

Treatment:

Drug: Riluzole

Drug: Masitinib (4.5)

Masitinib (6.0) & Riluzole

Experimental group

Description:

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.

Treatment:

Drug: Riluzole

Drug: Masitinib (6.0)

Placebo & Riluzole

Placebo Comparator group

Description:

Participants receive a matched dose placebo, given orally twice daily, in combination with riluzole at 50 mg b.i.d.

Treatment:

Drug: Riluzole

Drug: Placebo