piperidines and Multiple-Sclerosis--Chronic-Progressive

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). Study AB07002 assessed oral masitinib in patients with progressive MS who were progressing but not clinically active.. This randomized, double-blind, 2 parallel-group, placebo-controlled trial assessing 2 dose levels of masitinib vs equivalent placebo was conducted at 116 hospital clinics and specialized MS centers in 20 countries. Randomization (2:1) with minimization was performed centrally using an automated system. Patients, physicians, and outcome assessors remained masked to treatment group allocation. Patients with primary progressive MS (PPMS) or nonactive secondary progressive MS (nSPMS) without relapse for ≥2 years, aged 18-75 years, with baseline Expanded Disability Status Scale (EDSS) 2.0-6.0, and regardless of time from onset were treated for 96 weeks. The primary end point was overall EDSS change from baseline using repeated measures (generalized estimating equation, timeframe W12-W96, measured every 12 weeks), with positive values indicating increased clinical deterioration. Efficacy and safety were assessed in all randomly assigned and treated patients.. Masitinib (4.5 mg/kg/d) can benefit people with PPMS and nSPMS. A confirmatory phase 3 study will be initiated to substantiate these data.. The first participant was randomized to study AB07002 on August 25, 2011. The trial was registered with the European Clinical Trials Database (#EudraCT 2010-021219-17) on July 1, 2011 (clinicaltrialsregister.eu/ctr-search/trial/2010-021219-17/ES) and with ClinicalTrials.gov (#NCT01433497) on September 14, 2011 (clinicaltrials.gov/ct2/show/NCT01433497).. This study provides Class II evidence that masitinib 4.5 mg/kg/d decreased progression of disability, measured by the EDSS, in adults with PPMS or patients with nSPMS (with no exacerbations in the last 2 years).

Topics: Adolescent; Adult; Benzamides; Disease Progression; Double-Blind Method; Female; Humans; Male; Middle Aged; Multiple Sclerosis, Chronic Progressive; Outcome Assessment, Health Care; Piperidines; Protein Kinase Inhibitors; Pyridines; Thiazoles; Young Adult

Topics: Animals; Antibodies, Monoclonal, Humanized; Antigens, CD20; Azetidines; B-Lymphocytes; Benzamides; Benzyl Compounds; Blood-Brain Barrier; Clinical Trials as Topic; Disease Progression; Dogs; Drug Approval; Fingolimod Hydrochloride; Hope; Humans; Male; Mice; Multiple Sclerosis, Chronic Progressive; Neuroprotective Agents; Piperidines; Precision Medicine; Pyridines; Rituximab; Thiazoles; Ubiquinone; United States; United States Food and Drug Administration