A randomized, double-blind, 2 parallel-group, placebo-controlled, phase 3 trial investigated oral masitinib in people having progressive multiple sclerosis who were progressing but were not clinically active.

The study assessed two dose levels of masitinib (selective tyrosine kinase inhibitor) compared to equivalent placebo. Utilizing an automated system, randomization with minimization was carried out centrally. People having primary progressive multiple sclerosis or nonactive secondary progressive multiple sclerosis without relapse for ≥two years (aged 18-75 years), with baseline Expanded Disability Status Scale (EDSS) 2.0-6.0, and irrespective of time from onset were managed for ninety-six weeks.

The major outcome was overall EDSS alteration from baseline utilizing repeated measures, with positive values signifying raised clinical deterioration. Safety and effectiveness were evaluated in all the randomly allocated and treated people.

Overall, 611 people were randomly allocated to uptitrated masitinib 6.0 mg/kg/d parallel group (n=310) and masitinib 4.5 mg/kg/d parallel group (n=301). In terms of primary outcome, masitinib (4.5 mg/kg/d) (n = 199) demonstrated a remarkable benefit over placebo (n = 101).

Safety was found to be consistent with masitinib's known profile (rash, hematologic events, diarrhea, nausea), without any increased risk of infection. The effectiveness outcomes from independent uptitrated masitinib 6.0 mg/kg/d parallel group were not conclusive. No novel safety signal was noted.

Masitinib use reduced the advancement of disability, estimated by EDSS, in people with progressive forms of multiple sclerosis (without any exacerbations in the last two years).