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

April 14, 2023 updated by: AB Science

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

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 (Anticipated)

495

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Leuven, Belgium
        • Recruiting
        • University Hospital Leuven (UZ Leuven)
      • Copenhagen, Denmark
        • Recruiting
        • Bispebjerg Hospital
      • 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 - Hôpital 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
      • Ulm, Germany, 89081
        • Not yet recruiting
        • Department of Neurology, University of Ulm
      • Athens, Greece
        • Recruiting
        • Athens Naval Hospital
      • Athens, Greece
        • Recruiting
        • Eginition Hospital
      • Larissa, Greece
        • Recruiting
        • University General Hospital of Larissa
      • Río, Greece
        • Recruiting
        • General University Hospital of Patras
      • Jerusalem, Israel
        • Recruiting
        • Hadassah University Hospital
      • Tel Aviv, Israel
        • Recruiting
        • Tel-Aviv Medical Center Hôpital Sourasky (ICHILOV)
      • Brescia, Italy
        • Recruiting
        • ASST degli Spedali Civili di Brescia
      • Gussago, Italy
        • Recruiting
        • Centro Clinico NeMO Fondazione Serena Onlus
      • Milano, Italy
        • Recruiting
        • Istituti Clinici Scientifici Maugeri IRCCS
      • Milano, Italy
        • Recruiting
        • IRCCS Istituto Auxologico Italiano
      • Milano, Italy
        • Recruiting
        • Clinico Nemo Center (Centro Clinico NeMO Milano)
      • Milano, Italy
        • Recruiting
        • San Raffaele Hospital (Ospedale San Raffaele)
      • Novara, Italy
        • Recruiting
        • University Hospital Maggiore della Carita
      • Padova, Italy
        • Recruiting
        • Azienda Ospedale-Università 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
      • Oslo, Norway
        • Recruiting
        • Oslo University Hospital HF Ullevål
      • Bydgoszcz, Poland
        • Recruiting
        • Centrum Medyczne Neuromed
      • Lisboa, Portugal
        • Recruiting
        • Hospital de Santa Maria
      • Moscow, Russian Federation
        • Recruiting
        • Moscow city clinical Hospital after V.M. Buyanov
      • Novosibirsk, Russian Federation
        • Recruiting
        • Scientific Practical Medical Center "Innovation and Health"
      • Belgrad, Serbia
        • Recruiting
        • Clinical Centre of Serbia
      • Ljubljana, Slovenia
        • Recruiting
        • Klinicni center Ljubljana
      • 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 Politecnico La Fe
      • Karlstad, Sweden
        • Recruiting
        • Centralsjukhuset Karlstad (Central Hospital Karlstad)
      • Malmö, Sweden
        • Recruiting
        • Skåne University Hospital
      • Umeå, Sweden
        • Recruiting
        • Norrlands Universitetssjukhus
      • 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
    • 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
Riluzole 50 mg tablet, treatment per os
Other Names:
  • Rilutek
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.
Riluzole 50 mg tablet, treatment per os
Other Names:
  • Rilutek
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.
Riluzole 50 mg tablet, treatment per os
Other Names:
  • Rilutek
treatment per os
Other Names:
  • Placebo Oral Tablet

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ALSAQ-40
Time Frame: 48 weeks
Change in ALS quality of life patient questionnaire (ALSAQ-40)
48 weeks
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
From day of randomization to disease progression or death, assessed for a maximum of 36 months
FVC
Time Frame: 48 weeks
Change in Forced Vital Capacity (FVC)
48 weeks
HHD
Time Frame: 48 weeks
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
Time Frame: 48 weeks
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

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Albert Ludolph, MD, PhD, Department of Neurology, University of Ulm, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 2, 2021

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

December 1, 2023

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 (Actual)

April 18, 2023

Last Update Submitted That Met QC Criteria

April 14, 2023

Last Verified

April 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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