https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00660-0/fulltext Human African trypanosomiasis (HAT; also known as sleeping sickness) is caused by the protozoan parasite Trypanosoma brucei gambiense (gambiense HAT) and is transmitted by the tsetse fly. This neglected tropical disease is mostly fatal when left untreated. HAT remains endemic in sub-Saharan Africa, mainly in the Democratic Republic of the Congo, although surveillance and control programmes have achieved a steady decline in gambiense HAT incidence worldwide with 565 cases reported in 2020 (a decrease from 2110 cases in 2016). Acoziborole, an oral benzoxaborole-6-carboxamide from the Drugs for Neglected Diseases initiative (DNDi) drug discovery programme, showed high activity in vitro in both stages of gambiense HAT in murine models, and low toxicity and strong efficacy in preclinical studies allowing progression to phase 1. A first-in-human study (unpublished) showed the tolerability and pharmacokinetic profile of acoziborole and determined that a single therapeutic dose of 960 mg in fasted patients provided the desired exposure to the parasite in blood and cerebrospinal fluid (CSF) with a good safety profile. Here, we aim to assess the safety and efficacy of acoziborole in adult and adolescent patients with gambiense HAT.