Prospective Study on Efficacy and Safety of Acoziborole (SCYX-7158) in Patients Infected by Human African Trypanosomiasis Due to T.b. Gambiense

Study Overview
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Brief Summary
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The goal of this study is to assess efficacy and safety of Acoziborole (SCYX-7158) given as a single dose oral treatment for adult patients (above or equal 15) in the fasting state with T.b. Gambiense HAT

Official Title
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Efficacy and Safety Study of Acoziborole (SCYX-7158) in Patients With Human African Trypanosomiasis (HAT) Due to Trypanosoma Brucei Gambiense: a Multicentre, Open-label, Prospective Study

Conditions
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Trypanosomiasis, African, Gambiense Trypanosomiasis, Sleeping Sickness

Intervention / Treatment
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* Drug: Acoziborole (SCYX-7158)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patient 15 years of age or older Signed informed consent form (as well as assent from illiterate and under-age patients, and those unable to give consent) Karnofsky Performance Status above 50 Able to ingest oral tablets Having a permanent address or being traceable by other persons Able to comply with the schedule of follow-up visits and requirements of the study Agreement to be hospitalised in order to receive treatment For patients with late-stage HAT: Confirmation of g-HAT by detection of the parasite in the blood and/or the lymph and/or the CSF, at the investigational centre If trypanosomes are found in the blood or lymph, but not in the CSF, the CSF WBC, measured at the investigational centre, must be above 20/μL for the patient to be included in the cohort of patients with late-stage HAT For patients with early- or intermediate-stage HAT: Confirmation of g-HAT by detection of the parasite in the blood and/or the lymph, at the investigational centre Absence of parasites in the CSF The CSF WBC, measured at the investigational centre, must be between 6 and 20/μL for the patient to be included in the cohort of patients with intermediate-stage HAT and equal to or below 5/μL for the patient to be included in the cohort of patients with early-stage HAT. Exclusion Criteria: Severe malnourishment, defined as body-mass index (BMI) below 16 Pregnancy or breastfeeding (for women of child-bearing potential, confirmed pregnancy on a urine pregnancy test performed within 24 hours prior to administration of SCYX-7158) Clinically significant medical condition that could, in the opinion of the Investigator, jeopardise the patient's safety or interfere with participation in the study, including, but not limited to significant liver or cardiovascular disease, suspected or proven active infection, central nervous system trauma or seizure disorder, coma or consciousness disturbances Severely deteriorated health status, e.g. due to cardiovascular shock, respiratory distress syndrome or end-stage disease Previously treated for HAT (except prior treatment with pentamidine) Prior enrolment in the study Foreseeable difficulty complying with follow-up, including migrant worker, refugee status, itinerant trader etc. Current alcohol abuse or drug addiction Not tested for malaria and/or not having received appropriate treatment for malaria Not having received appropriate treatment for soil-transmitted helminthiasis Clinically significant abnormal laboratory values including Aspartate AminoTransferase(AST) and/or AlanineAminoTransferase (ALT) more than 2 times the upper limit of normal (ULN), total bilirubin more than 1.5 ULN, severe leukopenia at less than 2000/mm3, Potassium below 3.5 mmol/L, any other clinically significant abnormal laboratory value

Ages Eligible for Study
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Minimum Age: 15 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: Acoziborole (SCYX-7158)<br>Acoziborole (SCYX-7158), in 320-mg tablets, administered by the oral route to patients in the fasting state according to the following dosing regimen: 960 mg (3 tablets) in a single intake on Day 1. | Drug: Acoziborole (SCYX-7158)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success or failure for patients in late stage HAT | Success is defined as a cure, according to the criteria adapted from the World Health Organization(WHO) | 18 months follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success or failure for all stage HAT patients | Success is defined as a cure, according to the criteria adapted from the WHO | 6, 12 and 18 months follow up | 
| Time to Failure in Patients with Late-stage HAT | Time of the first objective evidence of failure. | 18 months follow up | 
| Occurence of adverse events | Occurrence of any Adverse Event, including an abnormal laboratory test result, during the observation period and until 6 month follow-up. | From day 1 until 6 months follow-up | 
| Occurence of serious advers events | Occurrence of any serious adverse events during the observation period and until 18 month follow-up | Between the day 1 and the end of the follow-up period (18 month) | 
| Pharmacokinetics measure | SCYX-7158 Area Under Curve in whole blood and in the Cerebrospinal fluid (CSF); | Days 1, 2, 3, 4, 5, 11, Month 3 and Month 6 follow up visits | 
| Pharmacokinetics measure | SCYX-7158 concentration in whole blood and in the Cerebrospinal fluid; | Days 1, 2, 3, 4, 5, 11, Month 3 and Month 6 follow up visits | 
| Electrocardiogram measure | PR interval | Days 1, 2, 3, 4, 5 and 11 | 
| Electrocardiogram measure | quantitative description of PR interval | Days 1, 2, 3, 4, 5 and 11 | 
| Electrocardiogram measure | quantitative description of RR interval | Days 1, 2, 3, 4, 5 and 11 | 
| Electrocardiogram measure | quantitative description of QRs interval | Days 1, 2, 3, 4, 5 and 11 | 
| Electrocardiogram measure | quantitative description of QTcF interval | Days 1, 2, 3, 4, 5 and 11 |