Clinical trial NCT05441488: Masitinib in the Treatment of Patients With Primary Progressive or Non-active Secondary Progressive Multiple Sclerosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Progressive Multiple Sclerosis
Keywords: Primary progressive MS
Non-active secondary progressive MS
Tyrosine kinase inhibitor
PPMS
SPMS
Lead sponsor: AB Science
Sponsor class: INDUSTRY
First posted: 2022-07-01
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to confirmed progression
timeFrame: 96 weeks
Secondary outcomes:
measure: Time to Expanded Disability Status Scale (EDSS) score of 7.0
timeFrame: 96 weeks
measure: Overall Change in Expanded Disability Status Scale (EDSS) Score
timeFrame: 96 weeks
measure: Brain Magnetic Resonance Imaging Assessments
timeFrame: 96 weeks
measure: Multiple Sclerosis Quality of Life (MSQOL)-54
timeFrame: 96 weeks
Other outcomes:
Locations:
city: Créteil
country: France
facility: Service de Neurologie Hôpital Henri-Mondor
city: Lille
country: France
facility: Hôpital Roger Salengro
city: Nice
country: France
facility: Hôpital Pasteur - CHU de Nice
city: Nîmes
country: France
facility: Centre Hospitalier Universitaire Nimes - Service de Neurologie
city: Poissy
country: France
facility: Centre hospitalier intercommunal de Poissy-Saint-Germain-en-Laye
city: Poitiers
country: France
facility: Le Centre hospitalier universitaire de Poitiers
city: Rouen
country: France
facility: Centre Hospitalier Universitaire de Rouen
city: Strasbourg
country: France
facility: Centre Hospitalier Universitaire de Strasbourg
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire Toulouse
city: Athens
country: Greece
facility: Athens Naval Hospital
city: Athens
country: Greece
facility: Eginition Hospital, Athens University Medical School
city: Larissa
country: Greece
facility: General University Hospital of Larissa
city: Thessaloníki
country: Greece
facility: AHEPA University Hospital, Aristotle University of Thessaloniki
city: Volos
country: Greece
facility: Private Clinic ELPIS
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico "G.Rodolico -San Marco"
city: Katowice
country: Poland
facility: Nzoz Neuro-Medic
city: Ksawerów
country: Poland
facility: NOVI-MED
city: Lublin
country: Poland
facility: NZOZ Neuro-Med
city: Oświęcim
country: Poland
facility: Generała Jarosława Dąbrowskiego
city: Poznań
country: Poland
facility: NZOZ Neuro-Kard
city: Warsaw
country: Poland
facility: Clinical Best Solutions
city: Łódź
country: Poland
facility: Centrum Neurologii Krzysztof Selmaj
city: Moscow
country: Russian Federation
facility: State Budgetary Institution of Health of the City of Moscow City Polyclinic #2
city: Perm
country: Russian Federation
facility: Perm Regional Clinical Hospital
city: Saint Petersburg
country: Russian Federation
facility: City Hospital No. 40 Kurortny District
city: Saint Petersburg
country: Russian Federation
facility: LLC "Center of socially significant diseases"
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Bilbao
country: Spain
facility: Hospital Universitario de Cruces
city: Madrid
country: Spain
facility: Gregorio Marañón General University Hospital
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
city: Stockholm
country: Sweden
facility: Centrum för neurologi
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Hospital
city: Rivne
country: Ukraine
facility: Rivne Regional Specialized Dispensary for Radiation Protection of the Population Municipal Enterprise
city: Ternopil
country: Ukraine
facility: Communal Non-Profit Enterprise "Ternopil Regional Clinical Psychoneurological Hospital" of Ternopil Regional Council, Department of Neurology #1
city: Vinnytsia
country: Ukraine
facility: Salutem Medical Center
Study officials:
affiliation: University of Lille, CHU of Lille, France
name: Patrick VERMERSCH, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.