Fexinidazole in Human African Trypanosomiasis Due to T. b. Rhodesiense

NCT ID: NCT03974178

Last Updated: 2025-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-29
• Study Completion Date: 2022-10-12

Brief Summary

The ultimate goal of this study is to show that fexinidazole offers an alternative over the existing treatments of Human African trypanosomiasis due to Trypanosoma brucei rhodesiense (r-HAT): melarsoprol in patients with stage 2 r-HAT and suramin in patients with stage 1 r-HAT. The main questions it aims to answer are:

• Is the short-term fatality rate and failure rate associated with fexinidazole lower than those of melarsoprol in patients with stage 2 r-HAT?
• Is the long-term failure rate associated with fexinidazole lower than that of melarsoprol in patients with stage 2 r-HAT?
• Can fexinidazole in patients with stage 1 r-HAT replace the treatment with suramin?
• Is fexinidazole treatment safe in patient with r-HAT, regardless of stage?

Participants will receive fexinidazole oral treatment for 10 days. Regular blood draws and lumbar punctures will be performed over 12 months to confirm the cure of the disease. Other assessments will include the recording of adverse events, signs and symptoms of the disease, laboratory tests, vital signs, electrocardiograms.

Conditions

Trypanosomiasis, African; Sleeping Sickness; Trypanosoma Brucei Rhodesiense; Infection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Patients with stage 1 r-HAT

Patients with stage 1 r-HAT were patients without trypanosomes in the cerebrospinal fluid (CSF) but with trypanosomes in the blood and/or lymph and CSF white blood cells (WBC) ≤5 cells/µL. Patients were to receive fexinidazole orally for 10 days.

Group Type: EXPERIMENTAL

Fexinidazole

Intervention Type: DRUG

Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)

Patients with stage 2 r-HAT

Patients with stage 2 r-HAT were patients with trypanosomes in the CSF (and/or in blood/lymph) and/or CSF WBC \>5 cells/µL. Patients were to receive fexinidazole orally for 10 days.

Group Type: EXPERIMENTAL

Fexinidazole

Intervention Type: DRUG

Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)

Interventions

Fexinidazole

Tablets of 600 mg; Participants with a weight between 20 and 34 kg received 1200 mg (2 tablets) for 4 days, then 600 mg (1 tablet) for 6 days (with food); Participants with a weight of 35 kg and above received 1800 mg (3 tablets) for 4 days, then 1200 mg (2 tablets) for 6 days (with food)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed Informed Consent Form (plus assent for children)
• ≥ 6 years old
• ≥ 20 kg body weight
• Ability to ingest at least one complete meal per day (or at least one Plumpy'Nut® sachet)
• Karnofsky index ≥ 40
• Parasitological confirmation of T. b. rhodesiense infection
• Having a permanent address or being traceable by others and willing and able to comply with follow-up visit schedule
• Agreement to be hospitalised for a minimum of 13 days and to receive the study treatment

Exclusion Criteria

• Active clinically relevant medical conditions other than HAT that may jeopardize subject safety or at the investigator discretion may interfere with participation in the study.
• Compromised general health or severely deteriorated general condition, such as severe malnutrition, cardiovascular shock, respiratory distress, or terminal illness
• Patients with severe hepatic impairment (e.g.: clinical signs of cirrhosis or jaundice)
• Known hypersensitivity to fexinidazole, to any nitroimidazole drugs (e.g. metronidazole, tinidazole), or to any of the excipients
• Patients previously enrolled in the study or having already received fexinidazole

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European and Developing Countries Clinical Trials Partnership (EDCTP)

OTHER_GOV

Sponsor Role: collaborator

Drugs for Neglected Diseases

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Enock Matovu, Prof

Role: PRINCIPAL_INVESTIGATOR

Makerere University

Locations

Rumphi District Hospital

Rumphi, , Malawi

Lwala Hospital

Lwala, Kadeberamaido, Uganda

Countries

Malawi; Uganda

References

Matovu E, Nyirenda W, Eriatu A, Alves D, Perdrieu C, Lemerani M, Wamboga C, Lejon V, Seixas J, Signorell A, Reymondier A, Baudin E, Scherrer B, Valverde Mordt O. Fexinidazole as a new oral treatment for human African trypanosomiasis due to Trypanosoma brucei rhodesiense: a prospective, open-label, single-arm, phase 2-3, non-randomised study. Lancet Glob Health. 2025 May;13(5):e910-e919. doi: 10.1016/S2214-109X(25)00016-6.

Reference Type: DERIVED

PMID: 40288400 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

DNDi-FEX-07-HAT

Identifier Type: -

Identifier Source: org_study_id