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An Open-Label Study of the Effectiveness and Safety of Fexinidazole for Gambiense Human African Trypanosomiasis, Including an Exploration of Adherence in Outpatients
28 Pages Posted: 18 Apr 2024
More...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 (g-HAT).
Methods: In this open-label study, the effectiveness and safety of fexinidazole was investigated in a wider population of patients than in previous trials. To confirm the feasibility of treating g-HAT outside the hospital setting, a cohort of patients treated at home was included. Patients with profiles excluded from earlier studies were included and treated in hospital (e.g., women in their second or third trimester of pregnancy, or breastfeeding). Fexinidazole was administered orally, as 600 mg tablets in a dose regimen dependent on bodyweight.
Findings: Between Nov 10, 2016, and Aug 10, 2019, 200 patients were screened, of whom 174 (87%) were included and received at least one dose of fexinidazole: 136 patients treated in hospital and 38 treated at home without direct medical supervision. All patients but one completed treatment. At 18 months, treatment was effective in 162 (93·1%) of 174 patients (95% confidence interval 88·3-96·4). No new safety signals were identified. This study has been completed and is registered with ClinicalTrials.gov, NCT03025789.
Interpretation: The effectiveness and safety of fexinidazole in this wider population was similar to that described in previous clinical trials, and treatment support by a briefed family member at home was shown to guarantee adequate treatment intake.
Trial Registration: This study was registered with ClinicalTrials.gov, NCT03025789.
Funding: The study was funded through DNDi and supported by grants from the Bill & Melinda Gates Foundation, UK International Development, UK (through the grant INV-008203); Dutch
Ministry of Foreign Affairs (DGIS), the Netherlands; Norwegian Agency for Development Cooperation (Norad), Norwegian Ministry of Foreign Affairs, as part of Norway’s in-kind contribution to EDCTP2, Norway; Federal Ministry of Education and Research (BMBF) through KfW, Germany; Stavros Niarchos Foundation (SNF), Médecins Sans Frontières International; Swiss Agency for Development Cooperation (SDC), Switzerland; Takeda Pharmaceutical Company Limited and other private foundations and individuals.
Declaration of Interest: BS reports personal fees from Drugs for Neglected Diseases initiative (DNDi) during the conduct of the study and personal fees from DNDi outside the submitted work. OVM, WMK, DNT, CP, CM, AR report employment at DNDi. All other authors declare no
competing interests.
Ethical Approval: The study protocol was approved by the Ethics Committee of the Protestant University in the DRC and the National Ethics Committee for Health Research in Guinea
Keywords: fexinidazole, phase IIIb, Democratic Republic of Congo, Guinea, trypanosomiasis, g-HAT, outpatient, Pregnant and breastfeeding women, children
Suggested Citation: Suggested Citation