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

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)

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).

Study Overview

• Status: Recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Riluzole; Drug: Masitinib (4.5); Drug: Masitinib (6.0); Drug: Placebo

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
• Enrollment (Estimated): 495
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Study Coordinator; Phone Number: +33(0)147200014; Email: clinical@ab-science.com

Study Locations

• Belgium
  • Leuven, Belgium
    • Recruiting
    • University Hospital Leuven (UZ Leuven)
• Denmark
  • Copenhagen, Denmark
    • Recruiting
    • Bispebjerg Hospital
• France
  • Angers, France
    • Recruiting
    • CHU de Angers
  • Bordeaux, France
    • Recruiting
    • Groupe Hospitalier Pellegrin Tripode
  • Bron, France
    • Recruiting
    • Hôpital Neurologique Pierre Wertheimer
  • Clermont-Ferrand, France
    • Recruiting
    • CHU Gabriel MONTPIED
  • Lille, France
    • Recruiting
    • CHU de Lille - Hôpital Roger Salengro
  • Limoges, France
    • Recruiting
    • CHU de Limoges - Hopital Dupuytren
  • Marseille, France
    • Recruiting
    • CHU de Marseille - Hôpital de la Timone
  • Montpellier, France
    • Recruiting
    • CHRU de Montpellier - Gui de Chauliac
  • Nancy, France
    • Recruiting
    • CHU de Nancy - Hôpital Central
  • Nice, France
    • Recruiting
    • CHU Hôpital Pasteur Nice
  • Tours, France
    • Recruiting
    • CHRU de Tours - Hôpital Bretonneau
• Germany
  • Ulm, Germany, 89081
    • Not yet recruiting
    • Department of Neurology, University of Ulm
• Greece
  • Athens, Greece
    • Recruiting
    • Athens Naval Hospital
  • Athens, Greece
    • Recruiting
    • Eginition Hospital
  • Larissa, Greece
    • Recruiting
    • University General Hospital of Larissa
  • Rio, Greece
    • Recruiting
    • General University Hospital of Patras
• Israel
  • Jerusalem, Israel
    • Recruiting
    • Hadassah University Hospital
  • Tel Aviv, Israel
    • Recruiting
    • Tel-Aviv Medical Center Hôpital Sourasky (ICHILOV)
• Italy
  • Brescia, Italy
    • Recruiting
    • ASST degli Spedali Civili di Brescia
  • Gussago, Italy
    • Recruiting
    • Centro Clinico NeMO Fondazione Serena Onlus
  • Milan, Italy
    • Recruiting
    • IRCCS Istituto Auxologico Italiano
  • Milan, Italy
    • Recruiting
    • Clinico Nemo Center (Centro Clinico NeMO Milano)
  • Milan, Italy
    • Recruiting
    • Istituti Clinici Scientifici Maugeri IRCCS
  • Milan, Italy
    • Recruiting
    • San Raffaele Hospital (Ospedale San Raffaele)
  • Novara, Italy
    • Recruiting
    • University Hospital Maggiore della Carita
  • Padua, Italy
    • Recruiting
    • Azienda Ospedale-Universita Padova
  • Pavia, Italy
    • Recruiting
    • IRCCS Mondino Foundation
  • Torino, Italy
    • Recruiting
    • University Hospital in Turin (Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino)
  • Modena
    • Baggiovara, Modena, Italy
      • Recruiting
      • Ospedale Civile Sant'Agostino - Estense
• Norway
  • Oslo, Norway
    • Recruiting
    • Oslo University Hospital HF Ullevål
• Poland
  • Bydgoszcz, Poland
    • Recruiting
    • Centrum Medyczne Neuromed
• Portugal
  • Lisbon, Portugal
    • Recruiting
    • Hospital de Santa Maria
• Russia
  • Moscow, Russia
    • Recruiting
    • Moscow city clinical Hospital after V.M. Buyanov
  • Novosibirsk, Russia
    • Recruiting
    • Scientific Practical Medical Center "Innovation and Health"
• Serbia
  • Belgrade, Serbia
    • Recruiting
    • Clinical Centre of Serbia
• Slovenia
  • Ljubljana, Slovenia
    • Recruiting
    • Klinicni center Ljubljana
• Spain
  • Alicante, Spain
    • Recruiting
    • Hospital General Universitario de Alicante
  • Barcelona, Spain
    • Recruiting
    • Hospital Universitari de Bellvitge
  • Madrid, Spain
    • Recruiting
    • Hospital Carlos III
  • Madrid, Spain
    • Recruiting
    • Hospital San Rafael
  • Santiago de Compostela, Spain
    • Recruiting
    • Clinical Hospital Santiago de Compostela
  • Valencia, Spain
    • Recruiting
    • Hospital Universitario y Politécnico La FE
• Sweden
  • Karlstad, Sweden
    • Recruiting
    • Centralsjukhuset Karlstad (Central Hospital Karlstad)
  • Malmo, Sweden
    • Recruiting
    • Skåne University Hospital
  • Umeå, Sweden
    • Recruiting
    • Norrlands universitetssjukhus
• Ukraine
  • Kharkiv, Ukraine
    • Recruiting
    • The State Institution of Neurology, Psychiatry and Narcology of NAMS of Ukraine
  • Kyiv, Ukraine
    • Recruiting
    • Medical Center of LLC Medical Center Dopomoga Plus
  • Lviv, Ukraine
    • Recruiting
    • Communal Non-Profit Enterprise of Lviv Regional Council, Lviv Regional Clinical Hospital, Neurological Department
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90007
      • Recruiting
      • University of Southern California
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • Recruiting
      • University of Kentucky
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Recruiting
      • Johns Hopkins Medicine Brain Science Institute
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Recruiting
      • Lahey Hospital and Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / 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 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: Riluzole; Riluzole 50 mg tablet, treatment per os; Other Names: Rilutek; Drug: Masitinib (6.0); Masitinib (titration to 6.0 mg/kg/day); Other Names: AB1010
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ALSFRS-R	Change in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ALSAQ-40	Change in ALS quality of life patient questionnaire (ALSAQ-40)	48 weeks
PFS	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	From day of randomization to disease progression or death, assessed for a maximum of 36 months
FVC	Change in Forced Vital Capacity (FVC)	48 weeks
HHD	Change in evaluation of upper- and lower-limb muscle strength using hand-held dynamometry (HHD)	48 weeks
Change in the Combined Assessment of Function and Survival (CAFS) score from baseline to week 48	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.	48 weeks

Collaborators and Investigators

• Sponsor: AB Science
• Investigators: Principal Investigator: Albert Ludolph, MD, PhD, Department of Neurology, University of Ulm, Germany

Publications and helpful links

General Publications

• Latham BD, Oskin DS, Crouch RD, Vergne MJ, Jackson KD. Cytochromes P450 2C8 and 3A Catalyze the Metabolic Activation of the Tyrosine Kinase Inhibitor Masitinib. Chem Res Toxicol. 2022 Sep 19;35(9):1467-1481. doi: 10.1021/acs.chemrestox.2c00057. Epub 2022 Sep 1.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2021
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: April 13, 2017
• First Submitted That Met QC Criteria: April 20, 2017
• First Posted (Actual): April 25, 2017

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; ALS; Tyrosine kinase inhibitor; Lou Gehrig's disease; Charcot's disease; Motor Neuron disease; MND
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Nutritional and Metabolic Diseases; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Substandard Drugs; Pharmaceutical Preparations; Thiazoles; Benzothiazoles; Azoles; Riluzole; Counterfeit Drugs; masitinib
• Other Study ID Numbers: AB19001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No