- Target disease: Chagas
- Clinical development: Phase II
- Partners (since project start): Eisai Co. Ltd, Japan; Platform of Integral Care for Patients with Chagas Disease, Spain/Bolivia; Universidad Mayor de San Simon, Bolivia; Universidad Autónoma Juan Misael Saracho, Bolivia; Collective of Applied Studies and Social Development (CEADES), Bolivia; NUDFAC – Nucleus of Pharmaceutical and Cosmetics Development, Brazil; Centre de Recerca en Salut Internacional de Barcelona (CRESIB), Spain; National Council of Scientific and Technological Research (INGEBI-CONICET), Argentina; Center for Tropical & Emerging Global Diseases, University of Georgia, USA; Cardinal Systems, France; Bioclinica, USA; Quantitative Solutions, USA
- Leadership: Head of Chagas Clinical Programme: Isabela Ribeiro; Project Coordinator: Bethania Blum; Clinical Monitor: Erika Correia
- Project start: February 2010
- Funding (since project start): Associação Bem-Te-Vi Diversidade, Brazil; Department for International Development (DFID), UK; Dutch Ministry of Foreign Affairs (DGIS), the Netherlands; Médecins Sans Frontières/Doctors without Borders, International; Ministry of Health, Brazil; Rockefeller Foundation, USA; Spanish Agency for International Development Cooperation (AECID), Spain; Swiss Agency for Development and Cooperation (SDC), Switzerland; Wellcome Trust, UK; Other private foundations and individuals.
- Project status: Completed
In 2009, DNDi joined forces with Eisai Co. Ltd – the Japanese pharmaceutical company that discovered E1224 – to develop this new chemical entity for Chagas disease. The Phase II proof-of-concept study started in July 2011 in Cochabamba and Tarija, Bolivia, the country which carries the world’s largest Chagas disease burden.
The study evaluated the potential of E1224 as a treatment for Chagas disease and explored promising biomarkers of therapeutic response in Chagas disease (see also Biomarkers project). This randomized, multicentre, placebo-controlled, safety and efficacy study evaluated three oral dosing regimens of E1224 and the standard dosing regimen of benznidazole (5mg/kg/day). The preliminary results, released in November 2013 at ASTMH, indicated that the experimental drug candidate E1224 was effective at clearing the parasite that causes Chagas disease at the end of the treatment course, but there was limited sustained efficacy one year after treatment as a single medication, as well as some safety issues at the highest dose. The current, standard therapy for Chagas, benznidazole, was shown to be very effective in the long term but continued to be associated with safety and tolerability concerns. While development of E1224 as monotherapy has been stopped, the focus has been shifted to exploring its use in a combination treatment for Chagas disease (see new benznidazole regimens and new combinations).
Key findings from the project:
- At treatment completion, PCR-determined eradication rates of the Chagas parasite were 79-91% for E1224; 91% for benznidazole; 26% for placebo.
- 12 months after treatment, 8-31% of patients treated with E1224 maintained parasite clearance compared with 81% with benznidazole and 8.5% placebo.
Last update: September 2014