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

NCT ID: NCT03127267

Last Updated: 2025-09-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

495 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-02-02

Study Completion Date

2027-12-31

Brief Summary

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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

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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).

Conditions

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Amyotrophic Lateral Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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

Group Type EXPERIMENTAL

Riluzole

Intervention Type DRUG

Riluzole 50 mg tablet, treatment per os

Masitinib (4.5)

Intervention Type DRUG

Masitinib (titration to 4.5 mg/kg/day)

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.

Group Type EXPERIMENTAL

Masitinib (6.0)

Intervention Type DRUG

Masitinib (titration to 6.0 mg/kg/day)

Riluzole

Intervention Type DRUG

Riluzole 50 mg tablet, treatment per os

Placebo & Riluzole

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

Group Type PLACEBO_COMPARATOR

Riluzole

Intervention Type DRUG

Riluzole 50 mg tablet, treatment per os

Placebo

Intervention Type DRUG

treatment per os

Interventions

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Masitinib (6.0)

Masitinib (titration to 6.0 mg/kg/day)

Intervention Type DRUG

Riluzole

Riluzole 50 mg tablet, treatment per os

Intervention Type DRUG

Placebo

treatment per os

Intervention Type DRUG

Masitinib (4.5)

Masitinib (titration to 4.5 mg/kg/day)

Intervention Type DRUG

Other Intervention Names

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AB1010 Rilutek Placebo Oral Tablet AB1010

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

81 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AB Science

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Albert Ludolph, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, University of Ulm, Germany

Locations

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Clinico Nemo Center (Centro Clinico NeMO Milano)

Milan, , Italy

Site Status RECRUITING

IRCCS Istituto Auxologico Italiano

Milan, , Italy

Site Status RECRUITING

Istituti Clinici Scientifici Maugeri IRCCS

Milan, , Italy

Site Status RECRUITING

San Raffaele Hospital (Ospedale San Raffaele)

Milan, , Italy

Site Status RECRUITING

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status RECRUITING

University of Southern California

Los Angeles, California, United States

Site Status RECRUITING

University of Kentucky

Lexington, Kentucky, United States

Site Status RECRUITING

Johns Hopkins Medicine Brain Science Institute

Baltimore, Maryland, United States

Site Status RECRUITING

Lahey Hospital and Medical Center

Burlington, Massachusetts, United States

Site Status RECRUITING

University of Virginia Health System

Charlottesville, Virginia, United States

Site Status RECRUITING

University Hospital Leuven (UZ Leuven)

Leuven, , Belgium

Site Status RECRUITING

Bispebjerg Hospital

Copenhagen, , Denmark

Site Status RECRUITING

CHU de Angers

Angers, , France

Site Status RECRUITING

Groupe Hospitalier Pellegrin Tripode

Bordeaux, , France

Site Status RECRUITING

Hôpital neurologique Pierre Wertheimer

Bron, , France

Site Status RECRUITING

CHU Gabriel Montpied

Clermont-Ferrand, , France

Site Status RECRUITING

CHU de Lille - Hopital Roger Salengro

Lille, , France

Site Status RECRUITING

CHU de Limoges - Hôpital Dupuytren

Limoges, , France

Site Status RECRUITING

CHU de Marseille - Hôpital de la Timone

Marseille, , France

Site Status RECRUITING

CHRU de Montpellier - Gui de Chauliac

Montpellier, , France

Site Status RECRUITING

CHU de Nancy - Hopital Central

Nancy, , France

Site Status RECRUITING

CHU Hôpital Pasteur Nice

Nice, , France

Site Status RECRUITING

CHRU de Tours - Hopital Bretonneau

Tours, , France

Site Status RECRUITING

Department of Neurology, University of Ulm

Ulm, , Germany

Site Status NOT_YET_RECRUITING

Athens Naval Hospital

Athens, , Greece

Site Status RECRUITING

Eginition Hospital

Athens, , Greece

Site Status RECRUITING

University General Hospital of Larissa

Larissa, , Greece

Site Status RECRUITING

General University Hospital of Patras

Rio, , Greece

Site Status RECRUITING

Hadassah University Hospital

Jerusalem, , Israel

Site Status RECRUITING

Tel-Aviv Medical Center Hôpital Sourasky (ICHILOV)

Tel Aviv, , Israel

Site Status RECRUITING

Ospedale Civile Sant'Agostino - Estense

Baggiovara, Modena, Italy

Site Status RECRUITING

ASST degli Spedali Civili di Brescia

Brescia, , Italy

Site Status RECRUITING

Centro Clinico NeMO Fondazione Serena Onlus

Gussago, , Italy

Site Status RECRUITING

University Hospital Maggiore della Carita

Novara, , Italy

Site Status RECRUITING

Azienda Ospedale-Università Padova

Padua, , Italy

Site Status RECRUITING

IRCCS Mondino Foundation

Pavia, , Italy

Site Status RECRUITING

University Hospital in Turin (Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino)

Torino, , Italy

Site Status RECRUITING

Oslo University Hospital HF Ullevål

Oslo, , Norway

Site Status RECRUITING

Centrum Medyczne Neuromed

Bydgoszcz, , Poland

Site Status RECRUITING

Hospital de Santa Maria

Lisbon, , Portugal

Site Status RECRUITING

Moscow city clinical Hospital after V.M. Buyanov

Moscow, , Russia

Site Status RECRUITING

Scientific Practical Medical Center "Innovation and Health"

Novosibirsk, , Russia

Site Status RECRUITING

Clinical Centre of Serbia

Belgrade, , Serbia

Site Status RECRUITING

Klinicni center Ljubljana

Ljubljana, , Slovenia

Site Status RECRUITING

Hospital General Universitario de Alicante

Alicante, , Spain

Site Status RECRUITING

Hospital Universitari de Bellvitge

Barcelona, , Spain

Site Status RECRUITING

Hospital Carlos III

Madrid, , Spain

Site Status RECRUITING

Hospital San Rafael

Madrid, , Spain

Site Status RECRUITING

Clinical Hospital Santiago de Compostela

Santiago de Compostela, , Spain

Site Status RECRUITING

Hospital Universitario y Politecnico La Fe

Valencia, , Spain

Site Status RECRUITING

Centralsjukhuset Karlstad (Central Hospital Karlstad)

Karlstad, , Sweden

Site Status RECRUITING

Skåne University Hospital

Malmo, , Sweden

Site Status RECRUITING

Norrlands universitetssjukhus

Umeå, , Sweden

Site Status RECRUITING

The State Institution of Neurology, Psychiatry and Narcology of NAMS of Ukraine

Kharkiv, , Ukraine

Site Status RECRUITING

Medical Center of LLC Medical Center Dopomoga Plus

Kyiv, , Ukraine

Site Status RECRUITING

Communal Non-Profit Enterprise of Lviv Regional Council, Lviv Regional Clinical Hospital, Neurological Department

Lviv, , Ukraine

Site Status RECRUITING

Countries

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United States Belgium Denmark France Germany Greece Israel Italy Norway Poland Portugal Russia Serbia Slovenia Spain Sweden Ukraine

Central Contacts

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Clinical Study Coordinator

Role: CONTACT

+33(0)147200014

References

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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.

Reference Type DERIVED
PMID: 36048877 (View on PubMed)

Other Identifiers

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AB19001

Identifier Type: -

Identifier Source: org_study_id

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