- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03127267
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
Status
Recruiting
Conditions
Intervention / Treatment
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
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Leuven, Belgium
- Recruiting
- University Hospital Leuven (UZ Leuven)
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Copenhagen, Denmark
- Recruiting
- Bispebjerg Hospital
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Angers, France
- Recruiting
- CHU de Angers
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Bordeaux, France
- Recruiting
- Groupe Hospitalier Pellegrin Tripode
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Bron, France
- Recruiting
- Hôpital Neurologique Pierre Wertheimer
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Clermont Ferrand, France
- Recruiting
- CHU Gabriel Montpied
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Lille, France
- Recruiting
- CHU de Lille - Hôpital Roger Salengro
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Limoges, France
- Recruiting
- CHU de Limoges - Hôpital Dupuytren
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Marseille, France
- Recruiting
- CHU de Marseille - Hôpital de la Timone
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Montpellier, France
- Recruiting
- CHRU de Montpellier - Gui de Chauliac
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Nancy, France
- Recruiting
- CHU de Nancy - Hôpital Central
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Nice, France
- Recruiting
- CHU Hôpital Pasteur Nice
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Tours, France
- Recruiting
- CHRU de Tours - Hôpital Bretonneau
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Ulm, Germany, 89081
- Not yet recruiting
- Department of Neurology, University of Ulm
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Athens, Greece
- Recruiting
- Athens Naval Hospital
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Athens, Greece
- Recruiting
- Eginition Hospital
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Larissa, Greece
- Recruiting
- University General Hospital of Larissa
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Río, Greece
- Recruiting
- General University Hospital of Patras
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Jerusalem, Israel
- Recruiting
- Hadassah University Hospital
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Tel Aviv, Israel
- Recruiting
- Tel-Aviv Medical Center Hôpital Sourasky (ICHILOV)
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Brescia, Italy
- Recruiting
- ASST degli Spedali Civili di Brescia
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Gussago, Italy
- Recruiting
- Centro Clinico NeMO Fondazione Serena Onlus
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Milano, Italy
- Recruiting
- Istituti Clinici Scientifici Maugeri IRCCS
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Milano, Italy
- Recruiting
- IRCCS Istituto Auxologico Italiano
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Milano, Italy
- Recruiting
- Clinico Nemo Center (Centro Clinico NeMO Milano)
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Milano, Italy
- Recruiting
- San Raffaele Hospital (Ospedale San Raffaele)
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Novara, Italy
- Recruiting
- University Hospital Maggiore della Carita
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Padova, Italy
- Recruiting
- Azienda Ospedale-Università Padova
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Pavia, Italy
- Recruiting
- IRCCS Mondino Foundation
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Torino, Italy
- Recruiting
- University Hospital in Turin (Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino)
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Modena
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Baggiovara, Modena, Italy
- Recruiting
- Ospedale Civile Sant'Agostino - Estense
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Oslo, Norway
- Recruiting
- Oslo University Hospital HF Ullevål
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Bydgoszcz, Poland
- Recruiting
- Centrum Medyczne Neuromed
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Lisboa, Portugal
- Recruiting
- Hospital de Santa Maria
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Moscow, Russian Federation
- Recruiting
- Moscow city clinical Hospital after V.M. Buyanov
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Novosibirsk, Russian Federation
- Recruiting
- Scientific Practical Medical Center "Innovation and Health"
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Belgrad, Serbia
- Recruiting
- Clinical Centre of Serbia
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Ljubljana, Slovenia
- Recruiting
- Klinicni center Ljubljana
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Alicante, Spain
- Recruiting
- Hospital General Universitario de Alicante
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Barcelona, Spain
- Recruiting
- Hospital Universitari de Bellvitge
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Madrid, Spain
- Recruiting
- Hospital Carlos III
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Madrid, Spain
- Recruiting
- Hospital San Rafael
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Santiago De Compostela, Spain
- Recruiting
- Clinical Hospital Santiago de Compostela
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Valencia, Spain
- Recruiting
- Hospital Universitario y Politecnico La Fe
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Karlstad, Sweden
- Recruiting
- Centralsjukhuset Karlstad (Central Hospital Karlstad)
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Malmö, Sweden
- Recruiting
- Skåne University Hospital
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Umeå, Sweden
- Recruiting
- Norrlands Universitetssjukhus
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Kharkiv, Ukraine
- Recruiting
- The State Institution of Neurology, Psychiatry and Narcology of NAMS of Ukraine
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Kyiv, Ukraine
- Recruiting
- Medical Center of LLC Medical Center Dopomoga Plus
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Lviv, Ukraine
- Recruiting
- Communal Non-Profit Enterprise of Lviv Regional Council, Lviv Regional Clinical Hospital, Neurological Department
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Alabama
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Birmingham, Alabama, United States, 35294
- Recruiting
- University of Alabama at Birmingham
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California
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Los Angeles, California, United States, 90007
- Recruiting
- University of Southern California
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Kentucky
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Lexington, Kentucky, United States, 40506
- Recruiting
- University of Kentucky
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Maryland
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Baltimore, Maryland, United States, 21205
- Recruiting
- Johns Hopkins Medicine Brain Science Institute
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Massachusetts
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Burlington, Massachusetts, United States, 01805
- Recruiting
- Lahey Hospital and Medical Center
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Virginia
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Charlottesville, Virginia, United States, 22903
- Recruiting
- University Of Virginia Health System
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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 |
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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
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Riluzole 50 mg tablet, treatment per os
Other Names:
Masitinib (titration to 4.5 mg/kg/day)
Other Names:
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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.
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Riluzole 50 mg tablet, treatment per os
Other Names:
Masitinib (titration to 6.0 mg/kg/day)
Other Names:
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Placebo Comparator: Placebo & Riluzole
Participants receive a matched dose placebo, given orally twice daily, in combination with riluzole at 50 mg b.i.d.
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Riluzole 50 mg tablet, treatment per os
Other Names:
treatment per os
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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ALSFRS-R
Time Frame: 48 weeks
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Change in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised.
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48 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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ALSAQ-40
Time Frame: 48 weeks
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Change in ALS quality of life patient questionnaire (ALSAQ-40)
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48 weeks
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PFS
Time Frame: From day of randomization to disease progression or death, assessed for a maximum of 36 months
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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
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From day of randomization to disease progression or death, assessed for a maximum of 36 months
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FVC
Time Frame: 48 weeks
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Change in Forced Vital Capacity (FVC)
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48 weeks
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HHD
Time Frame: 48 weeks
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Change in evaluation of upper- and lower-limb muscle strength using hand-held dynamometry (HHD)
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48 weeks
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Change in the Combined Assessment of Function and Survival (CAFS) score from baseline to week 48
Time Frame: 48 weeks
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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.
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48 weeks
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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
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Metabolic Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neuromuscular Diseases
- Neurodegenerative Diseases
- Spinal Cord Diseases
- TDP-43 Proteinopathies
- Proteostasis Deficiencies
- Sclerosis
- Motor Neuron Disease
- Amyotrophic Lateral Sclerosis
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Neuroprotective Agents
- Protective Agents
- Anticonvulsants
- Riluzole
Other Study ID Numbers
- AB19001
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
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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