- Target disease: HAT
- Main partners (since project start): Accelera, Italy; Amatsi Aquitaine (formerly Bertin Pharma), France; Aptuit, Italy; BaseCon A/S, Denmark; Biotrial, France; Bruno Scherrer, France; Cardiabase, France; CBCO, DRC; Institute of Tropical Medicine Antwerp, Belgium; Institut de Recherche pour le Développement, France; Institut National de Recherche Biomédicale, DRC; HAT Platform; Médecins Sans Frontières; National Control Programmes of the Democratic Republic of Congo, the Central African Republic, and Guinea; Phinc, France; Sanofi, France; SGS, Belgium; SGS, France; Swiss Tropical and Public Health Institute, Switzerland; WHO NTD Department, Switzerland.
- Project start: 2005
- Funding (since project start): Bill & Melinda Gates Foundation, USA; Brian Mercer Charitable Trust, UK; Dutch Ministry of Foreign Affairs (DGIS), The Netherlands; Federal Ministry of Education and Research (BMBF through KfW), Germany; French Development Agency (AFD), France; German Corporation for International Cooperation (GIZ) on behalf of the Government of the Federal Republic of Germany, Germany; Ministry of Foreign and European Affairs (MAEE), France; Médecins Sans Frontières/Doctors without Borders, International; Norwegian Agency for Development Cooperation (Norad), Norway; Republic and Canton of Geneva, International Solidarity Office, Switzerland; Spanish Agency for International Development Cooperation (AECID), Spain; Stavros Niarchos Foundation, USA; Swiss Agency for Development and Cooperation (SDC), Switzerland; UBS Optimus Foundation, Switzerland; UK aid UK; other private foundations and individuals.
Fexinidazole, the result of successful compound-mining efforts pursued by DNDi in 2005, entered clinical development in September 2009 and is being co-developed with Sanofi: DNDi is undertaking clinical and pharmaceutical development whilst Sanofi is responsible for the industrial development, production, and distribution. DNDi’s aim is to evaluate and register it as a treatment for a wide range of patients, specifically in adults and children over 6 years of age and 20kg body weight with either stage of disease. The first all-oral treatment for sleeping sickness, fexinidazole will be administered as one daily dose of pills for ten days and could remove the systematic hospitalization of patients. Fexinidazole was recommended by the European Medicines Agency in November 2018.
In January 2018, DNDi’s industrial partner Sanofi submitted a regulatory dossier to the European Medicines Agency (EMA) under Article 58 for the treatment of T.b. gambiense HAT (stages-1 and 2) in adults and children above the age of six and above 20kg. By involving the WHO and regulators from the DR Congo and Uganda in the EMA process, the use of Article 58 will enable faster in-country implementation of fexinidazole. The European Medicines Agency adopted a positive scientific opinion of fexinidazole in November 2018
Phase II/III study results published in 2017 confirmed that fexinidazole is safe and effective, and presents significant advantages over NECT, as it removes both the need for a lumbar puncture and systematic patient hospitalization. A regulatory dossier was submitted to the European Medicines Agency under Article 58 for the treatment of Trypanosoma brucei gambiense HAT (stages 1 and 2). Results were presented at ECTMIH in October 2017 and published in The Lancet.
The Phase IIIb trial that started in 2016 to obtain more information about special populations not included in previous fexinidazole trials is ongoing. Recruitment continued in 2017 with the inclusion of 45 patients (out of 174 in total) in five sites (Bandundu, Bagata, and Mushie, Masi Manimba, and Dipumba). Three more sites are planned to be opened in 2018, including one in Guinea.
Two additional complementary cohorts with fexinidazole were completed in 2016, one including 230 adult patients with stage 1 and early stage 2 of the disease, and another including 125 children between 6 and 14 years, both in DRC sites. Follow up of patients will be completed in 2017.
A Phase IIIb aiming at getting more information about special population groups not included in previous fexinidazole trials (including pregnant or lactating women, and patients with poor nutritional status or with chronic diseases) started in 2016. Patients will be treated either in hospital, or at home, thereby providing also preliminary information about the treatment compliance and final effectiveness in ambulatory patients. Three sites were initiated (Bandudu, Mushie and Bagata) and six patients (out of a target of 174) had been recruited by the end of 2016.
The results of the Phase II/III study support the submission of a regulatory dossier to the European Medicines Agency under Article 58, planned for late 2017 for the treatment of g-HAT with fexinidazole. It aims to facilitate faster WHO prequalification of the medicine as well as regulatory approvals and implementation in endemic countries. A risk management plan to further monitor safety and efficacy in the field is under preparation in collaboration with Sanofi and WHO.
In addition, the protocol for a study to be undertaken inr-HAT patients is being finalized, sites in Uganda and Malawi have been identified.
The pivotal Phase II/III study with fexinidazole completed this year, the recruitment of 394 stage 2 HAT patients at ten clinical sites in the Democratic Republic of Congo and the Central African Republic. A second study in adult patients with stage 1 and early stage 2 of the disease that was initiated in 2014 has recruited 228 patients to date. A third study in children between six and 14 years, also initiated in 2014, has recruited 125 patients to date.
Last update: November 2018