Date: 2013-10-02
Type of information:
phase: 2
Announcement: completion of patient recruitment
Company: Trophos (France)
Product: TRO40303
Action mechanism: mitochondria pore modulator The mechanism of action of TRO40303 involves prevention of stress-induced mitochondrial permeability transition, a target implicated in cardiac reperfusion injury. Studies reported by Trophos and colleagues recently in JPET (Schaller et al, http://www.ncbi.nlm.nih.gov/pubmed/20215409) show that TRO40303 binds directly to the cholesterol site of the mitochondrial outer membrane protein, TSPO, which is highly expressed in heart and is associated to the mitochondrial permeability transition pore, allowing rapid uptake of TRO40303 into cardiac tissue.
Disease: acute myocardial infarction
Therapeutic area: Cardiovascular diseases
Country:
Trial
details: The phase 2 proof of concept of TRO40303 is driven by Trophos and performed as part of the project MitoCare, funded by the European Union. MitoCare is led by a consortium of leading European investigators all having extensive experience in large-scale multicenter clinical trials in ischemia-reperfusion heart. The principal investigator is Professor Dan Atar, University Hospital of Oslo, Norway. This Phase 2 proof of concept is achieved versus placebo in patients undergoing coronary angioplasty (or balloon angioplasty) following an acute myocardial infarction. The TRO40303 is administered once intravenously just before reperfusion during angioplasty.
The primary endpoint of the study is the reduction of myocardial tissue damage. The level of damage is assessed by measuring cardiac proteins, Troponin I and CK that are released into the circulation. An additional major endpoint is the measurement of infarct size as a percentage of the at-risk myocardium, expressed by myocardial salvage index. This is assessed by cardiac magnetic resonance imaging (CMR) performed between three and five days after intervention.
Latest
news: * On October 2, 2013, Trophos has announced the final patient completion of a phase II study of TR040303 in patients treated for acute myocardial infarction (MI). Outcome data of this study is expected to be available towards the end of 2013. The Phase II proof-of-concept study has been designed to evaluate the efficacy and safety of Trophos TRO40303, a novel mitochondria pore modulator with broad cytoprotective properties, to treat cardiac ischemia-reperfusion injury (IRI) in acute myocardial infarction (MI) patients.The clinical study is part of the FP7 collaborative MitoCare project, granted EUR 6 million by the European Commission. The project is led by Trophos and operated by a consortium of 16 European institutions specializing in clinical and basic research, biomarkers, imaging and informatics.165 patients were enrolled in ten centers in four European countries, (France, Norway, Denmark and Sweden) in a double-blind, randomized, placebo-controlled study. Patients received an intravenous bolus of TRO40303 or matching placebo immediately preceding percutaneous coronary intervention (primary PCI) to treat a first acute STEMI.* On October 31, 2011, Trophos has started the Phase 2 proof of concept of its cardioprotective molecule TRO40303 in acute myocardial infarction. The first patient was treated in this study designed to evaluate the efficacy and safety of the molecule in the treatment of ischemia-reperfusion cardiac patients with acute myocardial infarction. This study is supported by the European project FP7, MitoCare. Results are expected by the end of 2012.
