- Target disease: Chagas
- Main partners (since project start): Centre de Recerca en Salut Internacional de Barcelona (CRESIB), Spain; Centro de Chagas y Patologia Regional, Hospital Independencia, Argentina; Collective of Applied Studies and Social Development (CEADES), Bolivia; Eisai Co., Ltd., Japan; FP Clinical Pharma – Ethel Feleder, Argentina; Fundación Mundo Sano and Laboratorio ELEA PHOENIX, Argentina; Hospital de Niños Dr Ricardo Gutiérrez, Argentina; IS Global, Institute for Global Health, Spain; Instituto Nacional de Epidemiología Dr Fatala Cháben, Argentina; LAT Research, Argentina; Luxembourg Institute of Health, Luxembourg; National Council of Scientific and Technological Research (INGEBI-CONICET), Argentina; NUDFAC – Nucleus of Pharmaceutical and Cosmetics Development, Brazil; PhinC, France; Platform of Integral Care for Patients with Chagas Disease, Spain/Bolivia; Universidad Autónoma Juan Misael Saracho, Bolivia; Universidad Mayor de San Simon, Bolivia.
- Project start: December 2013
- Funding (since project start): Department for International Development (DFID), UK; Federal Ministry of Education and Research (BMBF through KfW), Germany; Global Health Innovative Technology (GHIT) Fund, Japan; Médecins Sans Frontières/Doctors without Borders, International; Ministry of Foreign Affairs (DGIS), The Netherlands; Rockefeller Foundation, USA; Swiss Agency for Development and Cooperation (SDC), Switzerland; Starr International Foundation, Switzerland.
Benznidazole, the standard treatment for Chagas, has sustained efficacy until 12 months post-therapy, but is associated with side effects that can result in treatment discontinuation. In 2013, a proof-of-concept trial showed that fosravuconazole, an azole-class antifungal drug discovered by Eisai, had good safety and was effective at clearing the parasite, but efficacy was not sustained. A Phase I drug-drug interaction study assessed the safety and pharmacokinetic interactions of fosravuconazole and benznidazole administered separately and in combination. No major clinically relevant safety or tolerability issues were identified. A Phase II Proof of Concept trial was completed in 2018 and results will be available in early 2019.
This proof-of-concept trial was completed in the third quarter of 2018 and results will be available in early 2019. A total of 210 patients were recruited for this study, which was conducted in three sites in Bolivia and aims to improve efficacy, safety and tolerability of treatment of adults with chronic indeterminate Chagas. The trial assessed the efficacy of different doses of benznidazole in monotherapy and in combination with fosravuconazole. The primary measure of efficacy is a sustained parasitological response at six months follow-up with a final assessment at 12 months.
The trial is being conducted in three sites in Bolivia, with recruitment completed in late 2017. The primary efficacy parameter is sustained parasitological response at six months. The final assessment will include 12 months of follow-up, with final results available in early 2019.
Regulatory approvals were secured in Bolivia to start a Phase II Proof of Concept (PoC) study to determine if the safety (known as the “BENDITA” study) and tolerability issues of benznidazole could be managed by reduced doses and treatment duration, or by combining it with fosravuconazole. Benznidazole in monotherapy or in combination with fosravuconazole at selected doses and treatment durations will be assessed versus placebo in 210 patients with chronic Chagas disease. Recruitment started at the end of November; 10 patients had been enrolled by the end of 2016.
Last update: February 2019