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

Drugs for Neglected Diseases

Status and phase: Completed; Phase 3; Phase 2

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

Treatments: Drug: Fexinidazole

Study type: Interventional

Funder types: Other

Identifiers

NCT03974178

DNDi-FEX-07-HAT

Details and patient eligibility

About

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.

Enrollment: 45 patients

Sex: All

Ages: 6+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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45 participants in 2 patient groups

Patients with stage 1 r-HAT

Experimental group

Description:

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.

Treatment:

Drug: Fexinidazole

Patients with stage 2 r-HAT

Experimental group

Description:

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.

Treatment:

Drug: Fexinidazole