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Project Portfolio Azoles E1224 & Biomarker (Chagas)
Project Portfolio Azoles E1224 & Biomarker (Chagas)
Azoles E1224 & Biomarker (Chagas)
| • Target disease: Chagas • Clinical development: Phase II • Major Partners: Eisai Pharmaceuticals, Japan; Platform of Integral Care for Patients with Chagas Disease, Spain/Bolivia; Universidad Mayor de San Simon, Bolivia; Federal University of Ouro Preto, Brazil; INGEBI-CONICET, Argentina; MSF-Spain; Centre de Recerca en Salut Internacional de Barcelona (CRESIB), Spain; Universidad Autónoma Juan Misael Saracho, Bolivia; CEADES, Bolivia; NUDFAC, Brazil • Management: Head of Chagas Clinical Programme, Isabela Ribeiro; Clinical Manager, Fabiana Piovesan Alves; Project Coordinator, Bethania Blum • Project start: June 2008 • Funding: Médecins Sans Frontières/Doctors without Borders, International; Spanish Agency for International Development Cooperation (AECID), Spain; Department for International Development (DFID), UK; individual donors. |  Click for more | |
| DNDi received a EUR 2 Million Strategic Translation Award from the Wellcome Trust to develop E1224! Read Press Release |
Status: New antifungal azole derivatives offer a promising alternative treatment for Chagas disease. They potently inhibit T. cruzi ergosterol biosynthesis and possess desired pharmacokinetic properties (long terminal elimination half-life and large volume of distribution) suitable for the treatment of this disseminated intracellular infection. The current project evaluates E-1224, a new generation azole compound, as a new tool for the treatment of Chagas disease. E-1224 is a water-soluble monolysine salt form of a pro-drug of ravuconazole, which is rapidly converted to ravuconazole in vivo. Ravuconazole has been evaluated extensively in animal models and in human trials, including Phase II safety and efficacy studies for fungal infections. E-1224, discovered and developed by Eisai Pharmaceuticals, has completed pre-clinical evaluation and five Phase I clinical studies. DNDi and Eisai Pharmaceuticals (Japan) signed a collaboration and licensing agreement in September 2009. They will jointly conduct the safety and efficacy assessment of the compound in Chagas disease. DNDi is responsible for the clinical development to assess the safety and efficacy in patients with Chagas disease in endemic countries. In partnership with Eisai Pharmaceuticals and the Platform of Integral Care for Patients with Chagas Disease - that brings together scientists from CRESIB, Spain and universities in Bolivia - DNDi will start a Phase II study to evaluate safety and efficacy of E-1224 in (adult) patients with chronic indeterminate Chagas infection. Sites will be located in Bolivia, where Chagas is highly endemic. They have been properly equipped and staff received appropriated training during 2010. The protocol has been approved by three different ethical committees and sites will be ready to start recruitment by second quarter of 2011. Also in the scope of azoles compounds, DNDi will carry out, in partnership with the Federal University of Ouro Preto, Brazil, evaluations of the activity of ravuconazole in different strains of T. cruzi, in vivo and in vitro and in combination with benznidazole. A study is ongoing to optimize procedures for the use of the polymerase chain reaction (PCR) blood test as a measure of treatment response in Chagas disease. This study is being conducted in collaboration with MSF Spain, with PCR assay support provided by the Universidad Mayor de San Simon (UMSS) in Bolivia and quality assurance from INGEBI-CONICET in Buenos Aires, Argentina. In parallel, DNDi decided at the end of 2010 to start assessing biomarkers for Chagas disease with respect to their potential for application to clinical research (e.g. shortening of patient follow-up for test of cure, possible staging of the patients). This evaluation will be undertaken in 2011 in order to define a clear strategy for 2012 and years thereafter. |
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