Efficacy and Safety of Fexinidazole in Patients With Human African Trypanosomiasis (HAT) Due to Trypanosoma Brucei Rhodesiense

Study Overview
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Brief Summary
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This study aims at evaluating the efficacy and safety of a new oral treatment drug against Human African trypanosomiasis (HAT) due to T.b rhodesiense. 34 patients will be recruited in 2 sites located in Malawi and Uganda. All patients will receive the study drug fexinidazole.

Detailed Description
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Nowadays, the only treatment available for the stage 2 of HAT due to t.b rhodesiense is melarsoprol, a very toxic drug. The primary objective of this trial is to evaluate fexinidazole as an alternative treatment over melarsoprol in patients with stage 2 of HAT disease due to t.b rhodesiense in a Phase II/III cohort trial with 34 stage 2 patients. All stages of the disease will be recruited but the recruitment will stop once 34 evaluable stage-2 patients have reached the end of treatment. The trial will be a multicentre, non-randomized, clinical trial in patients with r-HAT. Subjects will be recruited among the patients reporting to Lwala Hospital (Uganda) and Rumphi District Hospital (Malawi). If feasible, r-HAT patients from other hospitals and centres in Kaberamaido/Dokolo Districts (Uganda) and Rumphi/Mzimba North District (Malawi) and well as Zambia bordering areas, will be referred to Lwala and Rumphi Hospitals, respectively, for treatment. Fexinidazole is an oral treatment which has to be taken every day for 10 days. In case of lack of efficacy (e.g. disease relapse) the patients will be switched to the standart treatment that is part of the National Control Program in each country (melarsoprol for stage-2 patients and suramin for stage-1 patients)

Official Title
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Efficacy and Safety of Fexinidazole in Patients With Human African Trypanosomiasis (HAT) Due to Trypanosoma Brucei Rhodesiense: a Multicentre, Open-label Clinical Trial

Conditions
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Trypanosoma Brucei Rhodesiense; Infection

Intervention / Treatment
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* Drug: Fexinidazole


Participation Criteria
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Eligibility Criteria
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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 confirmed 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 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 Patients with severe hepatic impairment (ex: clinical signs of cirrhosis or jaundice)

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fexinidazole<br>Patients with a body weight ≥ 35 kg: 1800 mg (3 tablets) from day 1 to 4 1200 mg (2 tablets) from day 5 to 10 Patients with a body weight ≥ 20 and < 35 kg: 1200 mg (2 tablets) from day 1 to 4 600 mg (1 tablet) from day 5 to 10 | Drug: Fexinidazole<br>* Adults and Children patients will receive fexinidazole tablets every day for 10 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Possibly Related fatality rate at the end of hospitalisation in stage 2 r-HAT patients | Death possibly related to r-HAT or treatment according to DSMB; since at the study sites anatomopathological techniques are not available, the completion of the WHO verbal autopsy questionnaire will be requested in case of death) | 12 to 18 days after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success rate at the End of Treatment in all stages patients | success is defined as: patient alive and no trypanosomes at end of treatment. Failure is defined as: presence of trypanosomes in any body fluid at end of treatment or death at End of hospitalization. Deaths to be considered are defined as possibly related to r-HAT or treatment according to DSMB. Unrelated deaths are neither success nor failure | 11 days after start of treatment | 
| Success and failure outcomes at the test of cure | A modification of the WHO recommendations is used to determine success and failure for stage-1 and stage-2 r-HAT patients (Appendix I - Evaluation criteria of efficacy endpoints) | 12 months after start of treatment | 
| Occurrence of adverse events and serious adverse events | 3. Occurrence of adverse events, including abnormal laboratory or ECG findings, during the observation period (until the end of hospitalisation scheduled up to 7 days after EOT) and those considered as possibly related to r-HAT or treatment, among those detected until the end of the follow-up period (12-month visit). All serious adverse events (SAE) whether they are considered as possibly related to r-HAT treatment or not. | 12 months after start of treatment | 
| Unsatisfactory clinical and parasitological response | defined as the compound analysis of the clinical evolution (symptoms of HAT) associated with presence of parasites in at least one body fluid (via blood test and/or lumbar puncture) | 11 days after start of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human African trypanosomiasis, neglected tropical disease, t.b. rhodesiense