Human African Trypanosomiasis Translation

 

  • Target disease: HAT
  • Main partners (since project start): Anacor Pharmaceuticals Inc, USA; Advinus Therapeutics Ltd, India; Avista Pharma (formerly SCYNEXIS), USA; Cardiabase, France; Creapharm, France; Eurofins-Optimed, France; HAT Platform; Institute of Tropical Medicine, Antwerp, Belgium; Institut de Recherche pour le Développement, France; Institut National de Recherche Biomédicale, DRC; Luxembourg Institute of Health, Luxembourg; National Trypanosomiasis Control Programme, DRC; Patheon, UK; PhinC, France; RCTs, France; SCYNEXIS Inc, USA; SGS, France; Swiss Tropical and Public Health Institute, Switzerland; Theradis Pharma, France.
  • Project start: January 2010
  • Funding (since project start): Bill & Melinda Gates Foundation, USA; Department for International Development (DFID), UK; Dutch Ministry of Foreign Affairs (DGIS), the Netherlands; Federal Ministry of Education and Research (BMBF through KfW), Germany; Médecins Sans Frontières/Doctors without Borders, International; Norwegian Government, Norway; Spanish Agency for International Development Cooperation (AECID), Spain; Swiss Agency for Development and Cooperation (SDC), Switzerland; BBVA Foundation, Spain; Other private foundations and individuals.

 

Overall Objective:

  • Develop and register acoziborole as a new drug for the treatment of stage 2 HAT caused by T. b. gambiense, ideally also for stage 1 HAT.

 

 

Acoziborole was selected as a pre-clinical candidate for g-HAT in late 2009. This resulted from DNDi’s own lead optimization project starting with an initial hit identified in the Anacor chemical library. In 2012, it became DNDi’s first new chemical entity resulting from its own lead optimization programme to enter clinical development. Acoziborole is expected to be administered directly at home.

A pivotal Phase II/III trial started in the last quarter of 2016. Seven study sites – Katanda, Isangi, Dipumba, Ngandajika, Masi Manimba, Kwamouth, and Bolobo – were initiated in Democratic Republic of Congo (DRC). Eleven patients (out of a target 350) had been recruited by the end of 2016.

The Phase I study with acoziborole was conducted and completed in 2015 in France. It assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of acoziborole after single oral ascending doses in 128 healthy human volunteers of sub-Saharan origin. It allowed for the therapeutic dose to be determined at 960 mg administered once as three tablets, with a favourable safety profile. As the drug has a long half-life (400 hours), the study was extended to ensure extensive safety monitoring of the healthy volunteers up to 210 days. This pharmacological finding has the advantage of translating into prolonged exposure with just one dose. These Phase I results confirm that the drug penetrates the brain, which is crucial to treat the late stage of the disease, where the parasite crosses the blood-brain barrier and kills patients if no treatment is given. Based on the results of this study, presented at the 9th European Congress on Tropical Medicine and International Health (ECTMIH) in September 2015, the single dose treatment will be tested in patients with stage 2 g-HAT in a Phase II/III trial, planned to start in the Democratic Republic of the Congo in 2016. The study will use several sites already active in fexinidazole development with addition of new sites selected from high-prevalence g-HAT areas. Patients will be followed up for 18 months after treatment to ensure long-lasting cure, with a preliminary evaluation of data performed after the first 12 months.

 

Last update: August 2017