Effectiveness and safety of fexinidazole for gambiense human African trypanosomiasis and exploration of adherence in outpatients: a phase 3b, prospective, open-label, non-randomised, cohort study

Abstract

Background: In previous clinical trials, oral fexinidazole treatment showed a favourable safety profile, while being easily administered and effective for most adult and paediatric patients with gambiense human African trypanosomiasis. The aim of this open-label cohort study was to investigate the effectiveness and safety of fexinidazole in a wider population of patients and to explore the feasibility of treating patients with gambiense human African trypanosomiasis outside the hospital setting.

Methods: In this phase 3b, prospective, open-label, non-randomised, cohort study, fexinidazole was administered orally as 600 mg tablets, in a dose regimen dependent on bodyweight. The study was conducted at eight treatment centres in the Democratic Republic of the Congo (seven of which enrolled patients) and one treatment centre in Guinea. Patients were either treated in hospital (in particular those excluded from earlier studies, such as women in their second or third trimester of pregnancy, or breastfeeding), or at home without direct medical supervision (but with the support of a caregiver). Patients were eligible for study inclusion if they met the following key criteria: aged at least 6 years; weighed at least 20 kg; had trypanosomes detected in any body fluid; had a Karnofsky performance status higher than 40%; were able to comply with the schedule of follow-up visits and with the study constraints; and were willing to undergo lumbar punctures. The primary endpoint was treatment outcome at 18 months, based on absence of parasites in lumbar puncture and blood, and overall clinical status. This study has been completed and is registered with ClinicalTrials.gov, NCT03025789.

Findings: Between Nov 10, 2016, and Aug 10, 2019, 200 patients were screened, of whom 174 (87%) were included and received at least one tablet of fexinidazole: 136 patients treated in hospital and 38 treated at home. All patients but one completed treatment. At 18 months, treatment was effective in 162 (93%) of 174 patients (95% CI 88·3-96·4). No new safety signals were identified, including in the 24 women who took fexinidazole before or during pregnancy or during breastfeeding. All outpatients complied with the dosing regimen, although three (8%) of 38 completed their treatment at the hospital.

Interpretation: The effectiveness and safety of fexinidazole in this wider population was similar to that described in previous clinical trials, and treatment at home seems feasible in selected patients who had the support of their caregiver.

Funding: Various donors through the Drugs for Neglected Diseases initiative.

Translation: For the French translation of the abstract see Supplementary Materials section.

Figure 1

Study flowchart of complete 18-month data