Determination of the Optimal Single Dose Treatment for Acoziborole, a Novel Drug for the Treatment of Human African Trypanosomiasis: First-in-Human Study.

Background And Objectives: Acoziborole is a novel boron-containing candidate developed as an oral drug for the treatment of human African trypanosomiasis (HAT). Results from preclinical studies allowed progression to Phase 1 trials. We aimed to determine the best dose regimen for all stages of HAT.

Efficacy and safety of acoziborole in patients with human African trypanosomiasis caused by Trypanosoma brucei gambiense: a multicentre, open-label, single-arm, phase 2/3 trial.

Background: Human African trypanosomiasis caused by Trypanosoma brucei gambiense (gambiense HAT) in patients with late-stage disease requires hospital admission to receive nifurtimox-eflornithine combination therapy (NECT). Fexinidazole, the latest treatment that has been recommended by WHO, also requires systematic admission to hospital, which is problematic in areas with few health-care resources. We aim to assess the safety and efficacy of acoziborole in adult and adolescent patients with gambiense HAT.

Trypanosome spliced leader RNA for diagnosis of acoziborole treatment outcome in gambiense human African trypanosomiasis: A longitudinal follow-up study.

Background: Detection of spliced leader (SL)-RNA allows sensitive diagnosis of gambiense human African trypanosomiasis (HAT). We investigated its diagnostic performance for treatment outcome assessment.

Methods: Blood and cerebrospinal fluid (CSF) from a consecutive series of 97 HAT patients, originating from the Democratic Republic of the Congo, were prospectively collected before treatment with acoziborole, and during 18 months of longitudinal follow-up after treatment.

Safety and efficacy of oral fexinidazole in children with gambiense human African trypanosomiasis: a multicentre, single-arm, open-label, phase 2-3 trial.

Background: Fexinidazole has been reported as an effective oral monotherapy against non-severe gambiense human African trypanosomiasis in a recent trial in adults. We aimed to assess the safety and efficacy of fexinidazole in children across all disease stages of gambiense human African trypanosomiasis.

Methods: We did a multicentre, single-arm, open-label, phase 2-3 trial at eight district hospitals in the Democratic Republic of the Congo.

Development and Introduction of Fexinidazole into the Global Human African Trypanosomiasis Program.

In this article, the authors show the strategy used to streamline the introduction of fexinidazole, the first all oral treatment of human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense. The dose range was determined in phase 1 studies and a significant food effect was observed, which was tested with field-adapted meals. The pharmacokinetic profile required definition of a higher loading dosage for the first 4 days and administration of the daily dose together with a typical local meal to optimize product absorption and rapidly achieve drug steady state.