Masitinib in the Treatment of Patients With Primary Progressive or Non-active Secondary Progressive Multiple Sclerosis
Study Details
Study Description
Brief Summary
To evaluate the efficacy and safety of oral masitinib versus placebo in the treatment of patients with primary progressive or secondary progressive multiple sclerosis without relapse.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
Detailed Description
Masitinib is a selective tyrosine kinase inhibitor, targeting innate immune cells (mast cells and microglia) that are involved in the pathophysiology of progressive multiple sclerosis (MS). This is a multicenter, double-blind, randomized, placebo-controlled, comparative study of oral masitinib in the treatment of patients with progressive MS who were progressing but not clinically active.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Masitinib (4.5) 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. |
Drug: Masitinib (4.5)
Masitinib (titration to 4.5 mg/kg/day)
Other Names:
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Placebo Comparator: Placebo Participants receive a matched dose placebo, given orally twice daily. |
Drug: Placebo
treatment per os
Other Names:
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Outcome Measures
Primary Outcome Measures
- Time to confirmed progression [96 weeks]
Time to disability progression, confirmed by two consecutive visits, wherein progression of disability is measured by the Expanded Disability Status Scale (EDSS) with progression defined as a 1-point worsening for baseline EDSS score ≤5.5, or 0.5-point worsening for baseline EDSS score >5.5. The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. The EDSS provides a total score on a scale that ranges from 0 to 10, in 0.5-point increments, with higher scores indicating greater disability. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability.
Secondary Outcome Measures
- Time to Expanded Disability Status Scale (EDSS) score of 7.0 [96 weeks]
Time to reach EDSS score of 7 from baseline up to week 96, wherein EDSS score of ≥7.0 represents wheelchair dependency. The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. The EDSS provides a total score on a scale that ranges from 0 to 10, in 0.5-point increments, with higher scores indicating greater disability. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability.
- Overall Change in Expanded Disability Status Scale (EDSS) Score [96 weeks]
Change from baseline on the EDSS, calculated using repeated measures methodology on all time points measured over 96 weeks (i.e., a population-averaged score comprising consecutive data points from each patient). The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. The EDSS provides a total score on a scale that ranges from 0 to 10, in 0.5-point increments, with higher scores indicating greater disability. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability.
- Brain Magnetic Resonance Imaging Assessments [96 weeks]
Change in baseline brain volume and lesions will be measured and assessed
- Multiple Sclerosis Quality of Life (MSQOL)-54 [96 weeks]
Change in quality of life assessment instrument MSQOL-54 The MS Quality of Life Instrument (MSQoL-54) is a structured self-report questionnaire that is used to assess the impact of MS on the individual's well-being. It consists of 52 items combined in 12 subscales, and two single items. Higher scores indicate a better quality of life.
Eligibility Criteria
Criteria
Main inclusion criteria include:
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Patients with either primary progressive or secondary progressive multiple sclerosis with onset of symptoms at least five years before baseline and with no relapse diagnosed according to the 2017 revised McDonald's criteria at least two years before screening
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Patients with Expanded Disability Status Scale (EDSS) score between 3.0 to 6.0 (both inclusive) at screening and baseline
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Patients with an EDSS score progression ≥1 point with no improvement during 2 years
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Absence of T1 Gadolinium-enhancing brain lesions as measured by MRI at screening
Main exclusion criteria include:
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Patients suffering from a disease other than MS that would better explain the patient's neurological clinical signs and symptoms and/or MRI lesions observed at screening
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Inability to complete screening MRI (contraindications for MRI) and/or any known allergy or hypersensitivity or any contra-indication to gadolinium macrocyclic
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Patients treated with other disease modifying treatments in the time frames and conditions mentioned under previous treatment wash out period, assessed at baseline
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Patients with lymphocytes <1.0 × 10^9/L at screening and at baseline
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Hôpital Roger Salengro | Lille | France | ||
2 | Centre Hospitalier Universitaire de Strasbourg | Strasbourg | France |
Sponsors and Collaborators
- AB Science
Investigators
- Principal Investigator: Patrick VERMERSCH, MD, PhD, University of Lille, CHU of Lille, France
Study Documents (Full-Text)
None provided.More Information
Publications
- Vermersch P, Benrabah R, Schmidt N, Zéphir H, Clavelou P, Vongsouthi C, Dubreuil P, Moussy A, Hermine O. Masitinib treatment in patients with progressive multiple sclerosis: a randomized pilot study. BMC Neurol. 2012 Jun 12;12:36. doi: 10.1186/1471-2377-12-36.
- Vermersch P, Brieva-Ruiz L, Fox RJ, Paul F, Ramio-Torrenta L, Schwab M, Moussy A, Mansfield C, Hermine O, Maciejowski M; AB07002 Study Group. Efficacy and Safety of Masitinib in Progressive Forms of Multiple Sclerosis: A Randomized, Phase 3, Clinical Trial. Neurol Neuroimmunol Neuroinflamm. 2022 Feb 21;9(3). pii: e1148. doi: 10.1212/NXI.0000000000001148. Print 2022 May.
- AB20009