The study is supported by the EU FP7 MitoTarget project (see below). The trial protocol has benefited from EMEA Scientific Advice procedure. Efficacy results are expected in the 4th quarter of 2011.
"The completion of recruitment of patients in this key clinical study is a great achievement and a major step in the development of olesoxime," said Jean-Louis Abitbol, Chief Medical Officer at Trophos. "Over 500 patients have been included in the study in only 9 months, which reflects the motivation and hard work of all involved and the commitment of the teams at the clinical sites."
"ALS urgently requires new therapies that can prolong survival and improve the patient's respiratory and muscular functions," said Damian Marron, CEO, Trophos. "We believe olesoxime could be a valuable new medicine for the ALS community and we look forward with great anticipation to the results of the trial in the fourth quarter of 2011."
Trial design and end-points
This phase 3 study is an 18-month randomized, parallel group, double-blind, placebo controlled trial evaluating the efficacy and safety of olesoxime against placebo in patients diagnosed with ALS between 6 and 36 months before enrolment who are already treated with riluzole. Olesoxime is dosed at 330 mg once a day, oral capsules and riluzole is dosed in both arms at 50 mg twice a day. The study is being undertaken in 15 centers in France, Germany, UK, Belgium and Spain.
The primary end-point of the study is the overall 18 month survival rate. Secondary end-points include the ALS Functional Rating Scale, time to assisted ventilation, vital capacity (a measure of respiratory function), Manual Muscular Testing and quality of life. Safety and tolerability is closely monitored and an independent Data Safety Monitoring Board is overseeing the trial.
The study is sponsored by Trophos and is being performed by a consortium of prominent European clinical investigators, all of whom have extensive prior experience conducting and collaborating in large multi-center clinical trials in ALS.
This clinical study of olesoxime is part of a three year collaborative project named MitoTarget (Grant Agreement No: HEALTH-F2-2008-223388). The European Commission has awarded a grant of nearly EUR 6 million for MitoTarget which is being carried out by a consortium led by Trophos. MitoTarget forms part of the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities. As well as the clinical trial, MitoTarget aims to enlarge the understanding of mitochondrial dysfunction in neurodegenerative diseases and assess the therapeutic potential of Trophos' novel proprietary class of mitochondrial pore modulator molecules in neurological diseases (see press release of 18 December, 2008).
Orphan drug designations
Trophos has been granted orphan drug designation for olesoxime for the treatment of ALS and SMA (spinal muscular atrophy) by the U.S. Food and Drug Administration and 'Orphan Medicinal Product' designation for both ALS and SMA by the European Commission in the EU.
Olesoxime (TRO19622) is the lead compound of Trophos' proprietary cholesterol-oxime compound family of mitochondrial pore modulators. Preclinical studies have demonstrated that the compounds promote the function and survival of neurons and other cell types under disease-relevant stress conditions through interactions with the mitochondrial permeability transition pore (mPTP); olesoxime has been shown to be active in the SOD1G93A mouse model of ALS (Bordet et al., JPET 322:709-720, 2007).
Olesoxime has successfully completed phase I studies in healthy volunteers and phase Ib studies in ALS patients. These clinical trials demonstrated that the product is well-tolerated and has an excellent safety profile. They also showed that once-a-day oral dosing achieves the predicted exposure level required for efficacy, based on preclinical models. Drug interaction studies with riluzole, the only registered treatment for ALS, showed no interaction of TRO19622 on riluzole pharmacokinetics.