Date: 2016-04-04
Type of information: Interim results
phase: 3
Announcement: interim results
Company: AB Science (France)
Product: masitinib
Action
mechanism: kinase inhibitor/tyrosine kinase inhibitor. Masitinib is a tyrosine kinase inhibitor that targets mast cells, important cells for immunity, as well as a limited number of kinases that play key roles in various cancers.
Disease: amyotrophic lateral sclerosis (ALS)
Therapeutic area: Neurodegenerative diseases - Rare diseases
Country: Spain
Trial details:
Latest
news: * On April 4, 2016, AB Science announced that a predefined interim analysis for its phase 3 randomized controlled trial evaluating masitinib in the treatment of amyotrophic lateral sclerosis has met its primary objective. Study AB10015 was a double-blind, placebo-controlled phase 2/3 study to compare the efficacy and safety of masitinib in combination with riluzole versus placebo in combination with riluzole in the treatment of patients suffering from amyotrophic lateral sclerosis . In accordance with study protocol, an interim analysis was planned to be performed once 191 of patients (50% of the study population) had reached the 48-week treatment time point. The interim analysis primary endpoint was based on the change from baseline to week 48 in the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). The ALSFRS-R score is a validated rating instrument for monitoring the progression of disability in patients with ALS, which correlates significantly with quality-of-life and survival. * On November 4, 2013, AB Science announces the initiation of a clinical development program with masitinib in the treatment of Amyotrophic Lateral Sclerosis (ALS). The clinical development program of masitinib in ALS started with a phase 2 clinical study, which involved the recruitment of 45 patients. Health authorities agreed to transform the phase 2 study into phase 3, with prospective recruitment of 210 patients. The readout of this study is expected by the end of 2015.
This endpoint is recommended by EMA and FDA guidelines for registration in ALS. Secondary analyses included change from baseline to week 48 in Forced Vital Capacity (FVC), which is an indicator of the respiratory function, and Combined Assessment of Function (CAFS), which is another validated endpoint ranking patients based on survival time and change in ALSFRS-R score.
The interim analysis was designed to be a success if the pre-specified difference between treatment groups could be detected with a p-value below 0.0311. The primary analysis was a success, with p-value < 0.01 in the intention-to-treat (ITT) population. All sensitivity analyses on the primary endpoint were also positive. The study was also successful on its secondary endpoints, FVC and CAFS. The frequency of adverse events (AEs), serious AEs, and AEs leading to discontinuation were similar between the two treatment arms.
According to preclinical studies conducted by Dr Luis Barbeito's laboratory at the Montevideo Pasteur Institute, masitinib's primary mechanism of action is to regulate abnormal neuroglia activation through the inhibition of a receptor called CSF-1R. Through this target, masitinib is able to inhibit glial cell proliferation and activation, including aberrant phenotypes that induce motor neuron death. As a secondary mechanism of action, masitinib acts on mast cells through the inhibition of the c-Kit/SCF and LYN/FYN signaling pathways. Consequently, masitinib is capable of modulating blood-brain barrier permeability and modulates also mast cell activity including mast cell microglia cross-talk, leading to a reduction in release of inflammatory mediators.
