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

NCT03127267 | Recruiting Phase 3 FDA Drug

• 1 other identifier: AB19001
• Study Type: interventional
• Target: 495
• Locations: 16 countries
• Sites: 55

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).

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic Lateral Sclerosis; ALS; Tyrosine kinase inhibitor; Lou Gehrig's disease; Charcot's disease; Motor Neuron disease; MND

Outcome Measures

Primary Outcomes (1)

• ALSFRS-R

  Change in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised.

  48 weeks

Secondary Outcomes (5)

• ALSAQ-40

  48 weeks

• PFS

  From day of randomization to disease progression or death, assessed for a maximum of 36 months

• FVC

  48 weeks

• HHD

  48 weeks

• Change in the Combined Assessment of Function and Survival (CAFS) score from baseline to week 48

  48 weeks

Study Arms (3)

Masitinib (4.5) & Riluzole

EXPERIMENTAL

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; Drug: Masitinib (4.5)

Masitinib (6.0) & Riluzole

EXPERIMENTAL

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); Drug: Riluzole

Placebo & Riluzole

PLACEBO COMPARATOR

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

Drug: Riluzole; Drug: Placebo

Interventions

Masitinib (6.0) DRUG

Masitinib (titration to 6.0 mg/kg/day)

Also known as: AB1010

Masitinib (6.0) & Riluzole

Riluzole DRUG

Riluzole 50 mg tablet, treatment per os

Also known as: Rilutek

Masitinib (4.5) & Riluzole; Masitinib (6.0) & Riluzole; Placebo & Riluzole

Placebo DRUG

treatment per os

Also known as: Placebo Oral Tablet

Placebo & Riluzole

Masitinib (4.5) DRUG

Masitinib (titration to 4.5 mg/kg/day)

Also known as: AB1010

Masitinib (4.5) & Riluzole

Eligibility Criteria

• Age: 18 Years - 81 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AB Science: lead

Study Sites (56)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

University of Southern California

Los Angeles, California, 90007, United States

RECRUITING

University of Kentucky

Lexington, Kentucky, 40506, United States

RECRUITING

Johns Hopkins Medicine Brain Science Institute

Baltimore, Maryland, 21205, United States

RECRUITING

Lahey Hospital and Medical Center

Burlington, Massachusetts, 01805, United States

RECRUITING

University of Virginia Health System

Charlottesville, Virginia, 22903, United States

RECRUITING

University Hospital Leuven (UZ Leuven)

Leuven, Belgium

RECRUITING

Bispebjerg Hospital

Copenhagen, Denmark

RECRUITING

CHU de Angers

Angers, France

RECRUITING

Groupe Hospitalier Pellegrin Tripode

Bordeaux, France

RECRUITING

Hôpital neurologique Pierre Wertheimer

Bron, France

RECRUITING

CHU Gabriel Montpied

Clermont-Ferrand, France

RECRUITING

CHU de Lille - Hopital Roger Salengro

Lille, France

RECRUITING

CHU de Limoges - Hôpital Dupuytren

Limoges, France

RECRUITING

CHU de Marseille - Hôpital de la Timone

Marseille, France

RECRUITING

CHRU de Montpellier - Gui de Chauliac

Montpellier, France

RECRUITING

CHU de Nancy - Hopital Central

Nancy, France

RECRUITING

CHU Hôpital Pasteur Nice

Nice, France

RECRUITING

CHRU de Tours - Hopital Bretonneau

Tours, France

RECRUITING

Department of Neurology, University of Ulm

Ulm, 89081, Germany

NOT YET RECRUITING

Athens Naval Hospital

Athens, Greece

RECRUITING

Eginition Hospital

Athens, Greece

RECRUITING

University General Hospital of Larissa

Larissa, Greece

RECRUITING

General University Hospital of Patras

Rio, Greece

RECRUITING

Hadassah University Hospital

Jerusalem, Israel

RECRUITING

Tel-Aviv Medical Center Hôpital Sourasky (ICHILOV)

Tel Aviv, Israel

RECRUITING

Ospedale Civile Sant'Agostino - Estense

Baggiovara, Modena, Italy

RECRUITING

ASST degli Spedali Civili di Brescia

Brescia, Italy

RECRUITING

Centro Clinico NeMO Fondazione Serena Onlus

Gussago, Italy

RECRUITING

Clinico Nemo Center (Centro Clinico NeMO Milano)

Milan, Italy

RECRUITING

IRCCS Istituto Auxologico Italiano

Milan, Italy

RECRUITING

Istituti Clinici Scientifici Maugeri IRCCS

Milan, Italy

RECRUITING

San Raffaele Hospital (Ospedale San Raffaele)

Milan, Italy

RECRUITING

University Hospital Maggiore della Carita

Novara, Italy

RECRUITING

Azienda Ospedale-Università Padova

Padua, Italy

RECRUITING

IRCCS Mondino Foundation

Pavia, Italy

RECRUITING

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

Torino, Italy

RECRUITING

Oslo University Hospital HF Ullevål

Oslo, Norway

RECRUITING

Centrum Medyczne Neuromed

Bydgoszcz, Poland

RECRUITING

Hospital de Santa Maria

Lisbon, Portugal

RECRUITING

Moscow city clinical Hospital after V.M. Buyanov

Moscow, Russia

RECRUITING

Scientific Practical Medical Center "Innovation and Health"

Novosibirsk, Russia

RECRUITING

Clinical Centre of Serbia

Belgrade, Serbia

RECRUITING

Klinicni center Ljubljana

Ljubljana, Slovenia

RECRUITING

Hospital General Universitario de Alicante

Alicante, Spain

RECRUITING

Hospital Universitari de Bellvitge

Barcelona, Spain

RECRUITING

Hospital Carlos III

Madrid, Spain

RECRUITING

Hospital San Rafael

Madrid, Spain

RECRUITING

Clinical Hospital Santiago de Compostela

Santiago de Compostela, Spain

RECRUITING

Hospital Universitario y Politecnico La Fe

Valencia, Spain

RECRUITING

Centralsjukhuset Karlstad (Central Hospital Karlstad)

Karlstad, Sweden

RECRUITING

Skåne University Hospital

Malmo, Sweden

RECRUITING

Norrlands universitetssjukhus

Umeå, Sweden

RECRUITING

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

Kharkiv, Ukraine

RECRUITING

Medical Center of LLC Medical Center Dopomoga Plus

Kyiv, Ukraine

RECRUITING

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

Lviv, Ukraine

RECRUITING

Related Publications (1)

• 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.

  PMID: 36048877 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Interventions

masitinib; Riluzole

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Albert Ludolph, MD, PhD

  Department of Neurology, University of Ulm, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Study Coordinator

CONTACT

+33(0)147200014; clinical@ab-science.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2017
• First Posted: April 25, 2017
• Study Start: February 2, 2021
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11); BE (1); ES (6); GR (4); IL (2); DE (1); PT (1); NO (1); SE (3); SL (1); RU (2); IT (11); DK (1); PL (1); US (6); UA (3)