Masitinib in the Treatment of Patients With Primary Progressive or Non-active Secondary Progressive Multiple Sclerosis (MAXIMS)

A 96-Week, Prospective, Multicenter, Randomised, Double-Blind, Placebo-Controlled, Phase 3 Study to Compare Efficacy and Safety of Masitinib Dose Titration to 4.5 mg/kg/Day Versus Placebo in the Treatment of Patients With Primary Progressive or Secondary Progressive Multiple Sclerosis Without Relapse

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.

Study Overview

• Status: Recruiting
• Conditions: Progressive Multiple Sclerosis
• Intervention / Treatment: Drug: Masitinib (4.5); Drug: Placebo

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 Type: Interventional
• Enrollment (Anticipated): 800
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Créteil, France
    • Recruiting
    • Service de Neurologie Hôpital Henri-Mondor
  • Lille, France
    • Recruiting
    • Hôpital Roger Salengro
  • Nice, France
    • Recruiting
    • Hôpital Pasteur - CHU de Nice
  • Nîmes, France
    • Recruiting
    • Centre Hospitalier Universitaire Nimes - Service de Neurologie
  • Poissy, France
    • Recruiting
    • Centre hospitalier intercommunal de Poissy-Saint-Germain-en-Laye
  • Poitiers, France
    • Not yet recruiting
    • Le Centre hospitalier universitaire de Poitiers
  • Rouen, France
    • Recruiting
    • Centre Hospitalier Universitaire de Rouen
  • Strasbourg, France
    • Recruiting
    • Centre Hospitalier Universitaire de STRASBOURG
  • Toulouse, France
    • Recruiting
    • Centre Hospitalier Universitaire Toulouse
• Greece
  • Athens, Greece
    • Not yet recruiting
    • Athens Naval Hospital
  • Athens, Greece
    • Not yet recruiting
    • Eginition Hospital, Athens University Medical School
  • Larissa, Greece
    • Not yet recruiting
    • General University Hospital of Larissa
  • Thessaloníki, Greece
    • Not yet recruiting
    • AHEPA University Hospital, Aristotle University of Thessaloniki
  • Volos, Greece
    • Recruiting
    • Private Clinic ELPIS
• Italy
  • Catania, Italy
    • Not yet recruiting
    • Azienda Ospedaliero Universitaria Policlinico "G.Rodolico -San Marco"
• Poland
  • Katowice, Poland
    • Recruiting
    • Nzoz Neuro-Medic
  • Ksawerów, Poland
    • Recruiting
    • NOVI-MED
  • Lublin, Poland
    • Recruiting
    • NZOZ Neuro-Med
  • Oświęcim, Poland
    • Recruiting
    • Generała Jarosława Dąbrowskiego
  • Poznań, Poland
    • Recruiting
    • NZOZ Neuro-kard
  • Warsaw, Poland
    • Not yet recruiting
    • Clinical Best Solutions
  • Łódź, Poland
    • Recruiting
    • Centrum Neurologii Krzysztof Selmaj
• Russian Federation
  • Moscow, Russian Federation
    • Recruiting
    • State Budgetary Institution of Health of the City of Moscow City Polyclinic #2
  • Perm, Russian Federation
    • Recruiting
    • Perm Regional Clinical Hospital
  • Saint Petersburg, Russian Federation
    • Recruiting
    • City Hospital No. 40 Kurortny District
  • Saint Petersburg, Russian Federation
    • Recruiting
    • LLC "Center of socially significant diseases"
• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital del Mar
  • Bilbao, Spain
    • Recruiting
    • Hospital Universitario de Cruces
  • Madrid, Spain
    • Recruiting
    • Hospital Clinico San Carlos
  • Madrid, Spain
    • Recruiting
    • Gregorio Marañón General University Hospital
  • Valencia, Spain
    • Recruiting
    • Hospital Universitario y Politecnico La Fe
• Sweden
  • Gothenburg, Sweden
    • Recruiting
    • Sahlgrenska University Hospital
  • Stockholm, Sweden
    • Recruiting
    • Centrum för Neurologi
• Ukraine
  • Lviv, Ukraine
    • Recruiting
    • Lviv Regional Clinical Hospital
  • Rivne, Ukraine
    • Recruiting
    • Rivne Regional Specialized Dispensary for Radiation Protection of the Population Municipal Enterprise
  • Ternopil, Ukraine
    • Recruiting
    • Communal Non-Profit Enterprise "Ternopil Regional Clinical Psychoneurological Hospital" of Ternopil Regional Council, Department of Neurology #1
  • Vinnytsia, Ukraine
    • Recruiting
    • Salutem Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main inclusion criteria include:

• 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
• Patients with Expanded Disability Status Scale (EDSS) score between 3.0 to 6.0 (both inclusive) at screening and baseline
• Patients with an EDSS score progression ≥1 point with no improvement during 2 years
• Absence of T1 Gadolinium-enhancing brain lesions as measured by MRI at screening

Main exclusion criteria include:

• 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
• Inability to complete screening MRI (contraindications for MRI) and/or any known allergy or hypersensitivity or any contra-indication to gadolinium macrocyclic
• Patients treated with other disease modifying treatments in the time frames and conditions mentioned under previous treatment wash out period, assessed at baseline
• Patients with lymphocytes <1.0 × 10^9/L at screening and at baseline

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: AB1010
Placebo Comparator: Placebo; Participants receive a matched dose placebo, given orally twice daily.	Drug: Placebo; treatment per os; Other Names: Placebo Oral Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to confirmed progression	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.	96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Expanded Disability Status Scale (EDSS) score of 7.0	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.	96 weeks
Overall Change in Expanded Disability Status Scale (EDSS) Score	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.	96 weeks
Brain Magnetic Resonance Imaging Assessments	Change in baseline brain volume and lesions will be measured and assessed	96 weeks
Multiple Sclerosis Quality of Life (MSQOL)-54	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.	96 weeks

Collaborators and Investigators

• Sponsor: AB Science
• Investigators: Principal Investigator: Patrick VERMERSCH, MD, PhD, University of Lille, CHU of Lille, France

Publications and helpful links

General Publications

• 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.
• 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):e1148. doi: 10.1212/NXI.0000000000001148. Print 2022 May.
• Vermersch P, Benrabah R, Schmidt N, Zephir 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2022
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: June 28, 2022
• First Submitted That Met QC Criteria: June 28, 2022
• First Posted (Actual): July 1, 2022

Study Record Updates

• Last Update Posted (Actual): March 30, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Tyrosine kinase inhibitor; SPMS; Primary progressive MS; Non-active secondary progressive MS; PPMS
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis
• Other Study ID Numbers: AB20009; MAXIMS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No