HAT-r-ACC logo

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 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.

T.b. rhodesiense is a more virulent 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 a month. T.b. rhodesiense sleeping sickness progresses more rapidly than T.b. gambiense sleeping sickness, causing death within months if untreated.

To provide clinical data to assess the safety and efficacy 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 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 account for 93% of T.b. rhodesiense cases globally. 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.

Cases of human African trypanosomiasis reported from Eastern and South-eastern Africa (period 2000-2009)
Cases of human African trypanosomiasis reported from Eastern and South-eastern Africa (period 2000-2009). Source

‘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

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.