Efficacy and Safety of Acoziborole (SCYX-7158) in Patients With Human African Trypanosomiasis Due to T.b. Gambiense (OXA002)

Drugs for Neglected Diseases

Status and phase: Completed; Phase 3; Phase 2

Conditions: Gambiense Trypanosomiasis; Sleeping Sickness; Trypanosomiasis, African

Treatments: Drug: Acoziborole

Study type: Interventional

Funder types: Other

Identifiers

NCT03087955

DNDi-OXA-02-HAT

Details and patient eligibility

About

The goal of this study is to assess efficacy and safety of acoziborole in adult participants with Trypanosoma brucei gambiense (T.b. gambiense) HAT, either early- or intermediate-stage HAT (first arm) or late-stage HAT (second arm). Participants will receive 3 tablets of 320 mg as a single oral dose of acoziborole in the fasting state on Day 1. Participants will stay in the hospital for observation for 15 days. In total, participants will be followed for 18 months.

Enrollment: 208 patients

Sex: All

Ages: 15+ years old

Volunteers: No Healthy Volunteers

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 acoziborole)
• 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 alanine aminotransferase (ALT) more than 2 times the upper limit of normal (ULN), total bilirubin more than 1.5 ULN, severe leukopenia at less than 2000/mm^3, Potassium below 3.5 mmol/L, any other clinically significant abnormal laboratory value

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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208 participants in 2 patient groups

Late-stage HAT

Experimental group

Description:

Participants with confirmation of HAT by detection of the parasite in the blood and/or lymph and/or cerebrospinal fluid (CSF) at the investigational center. If testing for parasites in CSF was negative, the CSF white blood cell count, measured at the investigational center, had to be above 20 cells/µL for classification as late-stage HAT. Participants received 960 mg acoziborole as a single oral dose.

Treatment:

Drug: Acoziborole

Early- and intermediate-stage HAT

Experimental group

Description:

Participants with confirmation of HAT by detection of the parasite in the blood and/or lymph at the investigational center. Parasites had to be absent from the CSF. The CSF white blood cell count, measured at the investigational center, had to be between 6 and 20 cells/µL for classification as intermediate stage HAT and equal to or below 5 cells/µL for classification as early-stage HAT. Participants received 960 mg acoziborole as a single oral dose.

Treatment:

Drug: Acoziborole