- Target disease: Chagas
- Main partners (since project start): Barcelona Centre for International Health Research, Spain; Dr Mario Fatala Chaben National Institute of Parasitology, Argentina; Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina; Infectious Diseases Data Observatory (IDDO), University of Oxford, UK; IS Global, Institute for Global Health, Spain; Leti, CEA, France; London School of Hygiene and Tropical Medicine, UK; McGill University, Canada; Médecins Sans Frontières; National Council of Scientific and Technological Research (INGEBI-CONICET), Argentina; NHEPACHA network; Texas Biomedical Research, USA; Universidad Autónoma Juan Misael Saracho, Bolivia; Universidad Mayor de San Simon, Bolivia; Universidad San Martin, Argentina; University Hospitals of Geneva, Switzerland; University of Georgia Research Foundation, USA; University of Texas at El Paso, USA.
- Project start: 2010
- Funding (since project start): 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; Spanish Agency for International Development Cooperation (AECID), Spain; Swiss Agency for Development and Cooperation (SDC), Switzerland; Wellcome Trust, UK; Other private foundations and individuals.
A Phase II Proof of Concept study of fexinidazole was initiated in 2014 in Cochabamba and Tarija, Bolivia. A total of 47 patients were included, but the study was interrupted due to safety and tolerability issues. Analyses of key outcomes demonstrated high efficacy findings at the lowest dose tested and for all treatment durations, with safety concerns about treatment at high doses tested for more than 14 days. In addition, acceptable safety and tolerability were found at low doses and short treatment durations. Taken together, these results warrant further investigation of fexinidazole for Chagas disease.
Current work is focusing on raising awareness among Chagas stakeholders about the need for biomarkers, with particular emphasis on regulatory aspects and the biomarker development process. Presentation of the Chagas Clinical Data Sharing Platform project (IDDO/DNDi) in plenary at the 2018 Chagas Platform Meeting in Santa Cruz was well received by clinicians. In parallel, the development of a prototype assay is ongoing for newly identified biomarkers – Apo A1 and Fbn fragments issued from a collaboration with McGill University – with InfYnity Biomarkers. The analysis of the NHEPACHA study data is pending and will be presented at the XV Chagas Disease Workshop organized by the Institute for Global Health Barcelona in March 2019.
Pre-clinical studies started in 2016 and were ongoing in 2017 to identify and validate potential biological markers of therapeutic response in Chagas patients. In addition, through the Ibero-American network NHEPACHA, DNDi is fostering work on testing four biomarkers to assess the response to Chagas treatment.
DNDi is collaborating with the University of Georgia and the Texas Biomedical Research Institute in a Wellcome Trust funded, non-human primate study in naturally infected animals with chronic Chagas disease, to further determine PCR and other markers as sensitive tools to consistently differentiate parasitological cure from treatment failure. The dosing period of the non-human primate study in naturally infected animals with chronic Chagas disease ended in 2015, and a 12-month follow-up assessment was completed in August 2015. The study immunosuppression phase was initiated in October 2015 and will end in mid-2016, at which point blood and tissue sample PCR and assessment of other biomarkers will be undertaken to determine if they can differentiate parasitological cure from treatment failure.
DNDi is a member of the NHEPACHA network of investigators created for the long-term cohort evaluation of potential biomarkers.
Last update: February 2019