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

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ClinicalTrials.gov Identifier: NCT03127267
Recruitment Status : Not yet recruiting
First Posted : April 25, 2017
Last Update Posted : December 10, 2018
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: Masitinib (6.0) Drug: Riluzole Drug: Placebo Drug: Masitinib (4.5) Phase 3

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).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 495 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Prospective, Multicenter, Randomised, Double-blind, Placebo-controlled, Parallel Groups, Phase 3 Study to Compare the Efficacy and Safety of Masitinib in Combination With Riluzole Versus Placebo in Combination With Riluzole in the Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis (ALS)
Estimated Study Start Date : May 2019
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2024


Arm Intervention/treatment
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 Name: Rilutek

Drug: Masitinib (4.5)
Masitinib (titration to 4.5 mg/kg/day)
Other Name: 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 Name: AB1010

Drug: Riluzole
Riluzole 50 mg tablet, treatment per os
Other Name: 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 Name: Rilutek

Drug: Placebo
treatment per os
Other Name: Placebo Oral Tablet




Primary Outcome Measures :
  1. ALSFRS-R [ Time Frame: 48 weeks ]
    Change in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised.


Secondary Outcome Measures :
  1. ALSAQ-40 [ Time Frame: 48 weeks ]
    Change in ALS quality of life patient questionnaire (ALSAQ-40)

  2. PFS [ Time Frame: 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

  3. FVC [ Time Frame: 48 weeks ]
    Change in Forced Vital Capacity (FVC)

  4. HHD [ Time Frame: 48 weeks ]
    Change in evaluation of upper- and lower-limb muscle strength using hand-held dynamometry (HHD)



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Ages Eligible for Study:   18 Years to 81 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03127267


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

Sponsors and Collaborators
AB Science
Investigators
Principal Investigator: Angela Genge, MD Montreal Neurological Institute and Hospital, Montreal, Canada

Responsible Party: AB Science
ClinicalTrials.gov Identifier: NCT03127267     History of Changes
Other Study ID Numbers: AB14008
First Posted: April 25, 2017    Key Record Dates
Last Update Posted: December 10, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AB Science:
Amyotrophic Lateral Sclerosis
ALS
Tyrosine kinase inhibitor
Lou Gehrig's disease
Charcot's disease
Motor Neuron disease
MND

Additional relevant MeSH terms:
Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Riluzole
Anticonvulsants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents