HAT-r-ACC - Efficacy and safety of fexinidazole in patients with Human African Trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense: a multicentre, open-label clinical trial
Project Abstract
A vector-borne parasitic illness, human African trypanosomiasis (HAT), also known as sleeping sickness, is usually fatal without treatment. The less prevalent form, T.b. rhodesiense (r-HAT), is concentrated in East Africa, with Malawi and Uganda reporting 88% of all cases worldwide between 2010-16.Treatment challenges for r-HAT abound, with the only option for stage-2 being a toxic, organo-arsenic drug (melarsoprol) and a less toxic, but very cumbersome to administer option (suramin) for stage-1. Issues of case detection, accessing patients, and the disease’s zoonotic nature exacerbate challenges in control and elimination efforts.
This five-year project aimed to address an urgent WHO-requested need to contribute to r-HAT control in East Africa by providing evidence for a new treatment to replace the highly toxic melarsoprol, and suramin. Based on clinical trial evidence showing the efficacy of fexinidazole in treating HAT caused by T.b. gambiense, this project extended to r-HAT patients, as well as enhance knowledge and addressed implementation gaps in r-HAT case detection and treatment.
Overall objective: To assess efficacy and facilitate access to fexinidazole: a potential new, safe, oral treatment for r-HAT patients in both stages of the disease
Secondary objectives:
- To show that fexinidazole offers an alternative over melarsoprol in stage 2 r-HAT patients, and over suramin in stage-1 r-HAT, through a clinical trial
- To ensure proper execution of the clinical trial through strengthening capacity of treatment and care
- To engage the local community to improve treatment access and extend case detection
- To manage all project components to achieve the overall objective
The 36-month clinical trial recruited 34 patients with stage-2 r-HAT (stage-1 patients were also to be included after a futility assessment) at two sites in Malawi and Uganda. The slow forecasted inclusion rate stems from the diminishing number of reported r-HAT cases. Training of local site personnel and optimization of clinical research infrastructure aimed to improve diagnosis and facilitate the gathering of scientific data. Finally, increasing awareness of r-HAT by fostering engagement within communities should encourage the uptake of trial results.
The development of fexinidazole for r-HAT, already proven successful in g-HAT, is a new tool to control and subsequently eliminate this neglected disease. The HAT-r-ACC project aligns with the overall objectives of EDCTP and supports the World Health Organization (WHO) HAT elimination target, and will help in achievement of the UN Sustainable Development Goal 3 to end by 2030 epidemics of neglected tropical diseases.
