Fexinidazole for T.b. rhodesiense
Fexinidazole for T.b. rhodesiense
To show that fexinidazole offers an alternative over melarsoprol in stage-2 r-HAT patients and over suramin in stage-1 r-HAT patients and to support case detection capacity and community awareness in Malawi and Uganda
current phase of drug development
updated 16 Feb 2023
DNDi’s long-term goal for sleeping sickness, also known as human African trypanosomiasis (HAT), is to develop and register two new drugs that are effective against both Stage 1 and Stage 2 of the disease and both subspecies of the parasite, T.b. gambiense and T.b. rhodesiense.
Fexinidazole, the first all-oral drug for sleeping sickness developed in clinical trials led by DNDi and added to the World Health Organization’s List of Essential Medicines for adults and children in July 2019, is currently only indicated as a treatment for T.b. gambiense sleeping sickness, the most common form of the disease. The 10-day once-a-day treatment can be taken at home under direct observation (DOT).
T.b. rhodesiense is an acute form of the disease, occurring primarily in Eastern and Southern Africa. Better treatments for T.b. rhodesiense sleeping sickness are urgently needed: the only treatment available for Stage 2 T.b. rhodesiense sleeping sickness is melarsoprol, a toxic arsenic drug dating from the 1940s that kills up to 5% of patients it is meant to cure. While the treatment option for Stage 1, suramin, is less toxic, it is difficult to administer, requiring five intravenous injections given every seven days for over a month. T.b. rhodesiense sleeping sickness progresses more rapidly than T.b. gambiense sleeping sickness, and often causes death within weeks or months if untreated.
To provide clinical data to assess the alternative use of fexinidazole as a treatment for both stages of T.b. rhodesiense, we have joined with partners to form the HAT-r-ACC consortium, with funding from the European & Developing Countries Clinical Trials Partnership (EDCTP) and the Portuguese Fundação para a Ciência e a Tecnologia. The consortium is working on a five-year project in Uganda and Malawi, which together accounted for 93% of T.b. rhodesiense cases globally when the project began. The clinical trial aims to support WHO control and elimination efforts in East Africa by providing evidence to extend the indication for fexinidazole to T.b. rhodesiense. The consortium also aims to support national sleeping sickness control programmes in Malawi and Uganda to raise awareness of T.b. rhodesiense sleeping sickness among affected communities and increase early detection of cases.
‘Patients scream as we inject the drug. Some never leave the hospital.’
Eunice is a nurse at Lwala Hospital, in Uganda, where melarsoprol, an arsenic-based treatment is still the only treatment available for stage two rhodesiense sleeping sickness
Project updates
2022
With the project entering its final year, the last patient in the clinical trial completed their last visit on 12 October 2022. The trial team began preparing an initial study report before the study was completed to accelerate preparation of the full dossier to be submitted to the European Medicines Agency (EMA) by DNDi industrial partner Sanofi for their opinion on extending the indication of fexinidazole to include treatment for sleeping sickness caused by T.b. rhodesiense. The first scientific article on the ethnographic studies was submitted in December 2022; three additional articles are in preparation. Case detection, training, and communication activities continued throughout the year.
2021
The Phase II/III study to evaluate the safety and efficacy of fexinidazole to treat T.b. rhodesiense sleeping sickness completed recruitment of all patients before the end of the year. The study will continue until the end of 2022 to allow for the follow-up of all patients for 12 months. Additional ethnographic studies were also conducted in Malawi and Uganda to explore the perceptions and practices of local communities and peripheral health centre staff regarding sleeping sickness, to inform interventions to improve rapid case detection and treatment. Posters and leaflets were developed within a large communication campaign to raise awareness of symptoms and the importance of rapid diagnosis and treatment.
2020
DNDi’s Phase II/III study continued in Malawi. In Uganda, the protocol was approved in December 2019, but the study was put on hold due to the COVID-19 pandemic. Recruitment will begin in 2021.
2019
To assess fexinidazole to treat HAT caused by T.b rhodesiense – the other, more virulent subspecies of the parasite affecting humans – a Phase II/III study that aims to enrol 34 stage two patients began with enrolment of the first patient in Malawi in October 2019. A total of 20 patients were enrolled by February 2020.
To provide clinical data to extend the indication to treat rhodesiense sleeping sickness with fexinidazole, we have joined with partners to form the HAT-r-ACC consortium with funding from the European & Developing Countries Clinical Trials Partnership. The consortium is working on a five-year project in Uganda and Malawi, which together account for 88% of rhodesiense sleeping sickness cases globally.
HAT-r-ACC consortium
The HAT-r-ACC consortium brings together a broad range of partners with expertise in sleeping sickness and capacity building in remote health settings. This research, training, and community engagement experience is essential to run the clinical trial in remote settings with a very small target population.
Social science studies
The HAT-r-ACC consortium run two social science studies in Malawi and Uganda to explore the perceptions and practices of local communities and peripheral health centre staff regarding sleeping sickness in order to improve case detection/referral and access to treatment. Read the report from Uganda:
Advocacy posters
Advocacy posters raising awareness about sleeping sickness were developed by the HAT-r-ACC consortium as part of a strategy to improve access to diagnosis and treatment of T.b. rhodesiense sleeping sickness in Malawi and Uganda.
Download advocacy posters for Uganda
Download advocacy posters for Malawi: in Chichewa / in Tumbuka
Presentations at the 10th EDCTP Forum
Additional resources
- Status of the trial on Clinical Trials.gov
- EDCTP publication on HAT-r-ACC
- Presentation on HAT-r-ACC and T.b. rhodesiense at the HNN 2.0 Training “International Cooperation and L&F issues in SC1” in May 2019
- Presentation on ‘Socio-cultural factors and experiences of r-HAT patients in Kaberamaido, Eastern Uganda: implications for treatment-seeking‘ at IHMT-WHO workshop/research seminar on HAT Elimination in July 2021
- Presentation on ‘Barriers to accessing treatment among patients with r-HAT around Vwaza Marsh wildlife reserve in Northern Malawi‘ at IHMT-WHO workshop/research seminar on HAT Elimination in July 2021
News & resources
- 22 February 2023 - HAT Platform Newsletter No. 22
- 23 December 2022 - 11 clinical trials that will shape medicine in 2023, Nature Medicine
- 1 February 2021 - Palmarès Prescrire 2020 des médicaments : trois médicaments primés, Prescrire
Funding
This project (grant RIA2017NCT-1846) is part of the European and Developing Countries Clinical Trials Partnership Association (EDCTP2) programme supported by the European Union.
Other funding:
Other private foundations and individuals
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