Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
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| ClinicalTrials.gov Identifier: NCT03127267 |
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Recruitment Status :
Recruiting
First Posted : April 25, 2017
Last Update Posted : April 18, 2023
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Sponsor:
AB Science
Information provided by (Responsible Party):
AB Science
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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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Amyotrophic Lateral Sclerosis | Drug: Masitinib (6.0) Drug: Riluzole Drug: Placebo Drug: Masitinib (4.5) | Phase 3 |
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 (Clinical Trial) |
| Estimated Enrollment : | 495 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | 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) |
| Actual Study Start Date : | February 2, 2021 |
| Estimated Primary Completion Date : | December 2023 |
| Estimated Study Completion Date : | December 2023 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Amyotrophic lateral sclerosis
Juvenile primary lateral sclerosis
MedlinePlus related topics:
Amyotrophic Lateral Sclerosis
Drug Information available for:
Riluzole
| 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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Drug: Riluzole
Riluzole 50 mg tablet, treatment per os
Other Name: Rilutek Drug: Masitinib (4.5) Masitinib (titration to 4.5 mg/kg/day)
Other Name: AB1010 |
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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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Drug: Masitinib (6.0)
Masitinib (titration to 6.0 mg/kg/day)
Other Name: AB1010 Drug: Riluzole Riluzole 50 mg tablet, treatment per os
Other Name: Rilutek |
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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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Drug: Riluzole
Riluzole 50 mg tablet, treatment per os
Other Name: Rilutek Drug: Placebo treatment per os
Other Name: Placebo Oral Tablet |
Primary Outcome Measures :
- ALSFRS-R [ Time Frame: 48 weeks ]Change in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised.
Secondary Outcome Measures :
- ALSAQ-40 [ Time Frame: 48 weeks ]Change in ALS quality of life patient questionnaire (ALSAQ-40)
- 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
- FVC [ Time Frame: 48 weeks ]Change in Forced Vital Capacity (FVC)
- HHD [ Time Frame: 48 weeks ]Change in evaluation of upper- and lower-limb muscle strength using hand-held dynamometry (HHD)
- 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.
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| Ages Eligible for Study: | 18 Years to 81 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03127267
Contacts
| Contact: Clinical Study Coordinator | +33(0)147200014 | clinical@ab-science.com |
Locations
Show 56 study locations
Sponsors and Collaborators
AB Science
Investigators
| Principal Investigator: | Albert Ludolph, MD, PhD | Department of Neurology, University of Ulm, Germany |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | AB Science |
| ClinicalTrials.gov Identifier: | NCT03127267 |
| Other Study ID Numbers: |
AB19001 |
| First Posted: | April 25, 2017 Key Record Dates |
| Last Update Posted: | April 18, 2023 |
| Last Verified: | April 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AB Science:
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Amyotrophic Lateral Sclerosis ALS Tyrosine kinase inhibitor Lou Gehrig's disease |
Charcot's disease Motor Neuron disease MND |
Additional relevant MeSH terms:
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Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis Pathologic Processes Neurodegenerative Diseases Nervous System Diseases Neuromuscular Diseases Spinal Cord Diseases Central Nervous System Diseases TDP-43 Proteinopathies Proteostasis Deficiencies |
Metabolic Diseases Riluzole Anticonvulsants Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Neuroprotective Agents Protective Agents |