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

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

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.

Study Overview

• Status: Completed
• Conditions: Trypanosomiasis, African; Gambiense Trypanosomiasis; Sleeping Sickness
• Intervention / Treatment: Drug: Acoziborole

• Study Type: Interventional
• Enrollment (Actual): 208
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Democratic Republic of the Congo
  • Bandundu Province, Democratic Republic of the Congo
    • Hopital Général de Réference de Bandundu
  • Isangi, Democratic Republic of the Congo
    • Hôpital de Référence d'Isangi
  • Kinshasa, Democratic Republic of the Congo
    • Hôpital Général de Référence Roi Baudouin
  • Bandundu
    • Nkara, Bandundu, Democratic Republic of the Congo
      • Centre de Traitement de Nkara
  • Bas-Congo Province
    • Kimpese, Bas-Congo Province, Democratic Republic of the Congo
      • Centre de Traitement de Kimpese
  • East Kasai
    • Gandajika, East Kasai, Democratic Republic of the Congo
      • Hôpital Général de Référence de Ngandajika
    • Katanda, East Kasai, Democratic Republic of the Congo
      • Hôpital Secondaire de Katanda
    • Mbuji-Mayi, East Kasai, Democratic Republic of the Congo
      • Hôpital de Dipumba
  • Kwilu
    • Bagata, Kwilu, Democratic Republic of the Congo
      • Hôpital Général de Référence de Bagata
    • Masi-Manimba, Kwilu, Democratic Republic of the Congo
      • Hôpital Général de Référence de Masi-Manimba
  • Mai Ndombe
    • Kwamouth, Mai Ndombe, Democratic Republic of the Congo
      • Hôpital Général de Référence de Kwamouth
• Guinea
  • Dubreka
    • Dubréka, Dubreka, Guinea
      • Centre de Traitement de la THA de Dubreka

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Late-stage HAT; 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.	Drug: Acoziborole; Acoziborole 3 x 320 mg tablets (fasted state); Other Names: SCYX-7158
Experimental: Early- and intermediate-stage HAT; 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.	Drug: Acoziborole; Acoziborole 3 x 320 mg tablets (fasted state); Other Names: SCYX-7158

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was a Success at Month 18 According to Adapted World Health Organization (WHO) Criteria	Success was defined according to an algorithm based on the criteria adapted from the WHO Recommendations of the Informal Consultation on Issues for Clinical Product Development for Human African Trypanosomiasis 2007 (WHO/CDS/NTD/IDM/2007.1). Success was defined as a cure or a probable cure. Failure was defined as a relapse, probable relapse, death, use of rescue medication, loss to follow-up, refusal of all post-treatment lumbar puncture, and, in the absence of lumbar puncture at the Month 18 visit, an unfavorable outcome earlier than Month 18, or signs and symptoms evoking a relapse at Month 18. An estimate of the percentage of participants whose treatment outcome was a success at Month 18 and the 95% Jeffreys confidence interval (CI) of the estimate were provided.	18 months post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was a Success at Month 12 According to Adapted WHO Criteria	Success was defined according to an algorithm based on the criteria adapted from the WHO Recommendations of the Informal Consultation on Issues for Clinical Product Development for Human African Trypanosomiasis 2007 (WHO/CDS/NTD/IDM/2007.1). Success was defined as a cure or a probable cure. Failure was defined as a relapse, probable relapse, death, use of rescue medication, loss to follow-up, refusal of all post-treatment lumbar puncture, and, in the absence of lumbar puncture at the end of Month 12, an unfavorable outcome earlier than end of Month 12, or signs and symptoms evoking a relapse at end of Month 12. For participants who continued after Month 12, data after Month 12 were considered in the algorithm. An estimate of the percentage of participants whose treatment outcome was a success at Month 12 and the 95% Jeffreys CI of the estimate were provided.	12 months post-dose
Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was a Success at Month 6 According to Adapted WHO Criteria	Success was defined according to an algorithm based on to the criteria adapted from the WHO Recommendations of the Informal Consultation on Issues for Clinical Product Development for Human African Trypanosomiasis 2007 (WHO/CDS/NTD/IDM/2007.1). Success was defined as a cure or a probable cure. Failure was defined as a relapse, probable relapse, death, use of rescue medication, loss to follow-up, refusal of all post-treatment lumbar puncture, and, in the absence of lumbar puncture at the end of Month 6, an unfavorable outcome earlier than end of Month 6, or signs and symptoms evoking a relapse at end of Month 6. For participants who continued after Month 6, data after Month 6 were considered in the algorithm. An estimate of the percentage of participants whose treatment outcome was a success at Month 6 and the 95% Jeffreys CI of the estimate were provided.	6 months post-dose
Percentage of Participants With Early- and Intermediate-stage HAT Whose Treatment Outcome Was a Success at Month 18 According to Adapted WHO Criteria	Success was defined according to an algorithm based on the criteria adapted from the WHO Recommendations of the Informal Consultation on Issues for Clinical Product Development for Human African Trypanosomiasis 2007 (WHO/CDS/NTD/IDM/2007.1). Success was defined as a cure or a probable cure. Failure was defined as a relapse, probable relapse, death, use of rescue medication, loss to follow-up, refusal of all post-treatment lumbar puncture, and, in the absence of lumbar puncture at the end of Month 18, an unfavorable outcome earlier than end of Month 18, or signs and symptoms evoking a relapse at end of Month 18. An estimate of the percentage of participants whose treatment outcome was a success at Month 18 and the 95% Jeffreys CI of the estimate were provided.	18 months post-dose
Percentage of Participants With Early- and Intermediate-stage HAT Whose Treatment Outcome Was a Success at Month 12 According to Adapted WHO Criteria	Success was defined according to an algorithm based on the criteria adapted from the WHO Recommendations of the Informal Consultation on Issues for Clinical Product Development for Human African Trypanosomiasis 2007 (WHO/CDS/NTD/IDM/2007.1). Success was defined as a cure or a probable cure. Failure was defined as a relapse, probable relapse, death, use of rescue medication, loss to follow-up, refusal of all post-treatment lumbar puncture, and, in the absence of lumbar puncture at the end of Month 12, an unfavorable outcome earlier than end of Month 12, or signs and symptoms evoking a relapse at end of Month 12. For participants who continued after Month 12, data after Month 12 were considered in the algorithm. An estimate of the percentage of participants whose treatment outcome was a success at Month 12 and the 95% Jeffreys CI of the estimate were provided.	12 months post-dose
Percentage of Participants With Early- and Intermediate-stage HAT Whose Treatment Outcome Was a Success at Month 6 According to Adapted WHO Criteria	Success was defined according to an algorithm based on the criteria adapted from the WHO Recommendations of the Informal Consultation on Issues for Clinical Product Development for Human African Trypanosomiasis 2007 (WHO/CDS/NTD/IDM/2007.1). Success was defined as a cure or a probable cure. Failure was defined as a relapse, probable relapse, death, use of rescue medication, loss to follow-up, refusal of all post-treatment lumbar puncture, and, in the absence of lumbar puncture at the end of Month 6, an unfavorable outcome earlier than end of Month 6, or signs and symptoms evoking a relapse at end of Month 6. For participants who continued after Month 6, data after Month 6 were considered in the algorithm. An estimate of the percentage of participants whose treatment outcome was a success at Month 6 and the 95% Jeffreys CI of the estimate were provided.	6 months post-dose
Estimated Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was Not a Proven Failure at Month 18, Based on the Kaplan-Meier Analysis of Time to Proven and Definitive Failure	Failure was defined as the first objective evidence of proven and definitive (sustainable) failure, defined as death; rescue medication use; trypanosomes in any body fluid at Month 6, 12, or 18; a cerebrospinal fluid (CSF) white blood cell count (WBC) of >50 cells/μL at Month 6 followed by confirmation of failure (defined as CSF WBC >20 cells/μL at Month 12 and/or Month 18 and/or signs and symptoms evoking a relapse at Month 12 and/or Month 18); a CSF WBC >20 cells/μL at Month 12 followed by confirmation of failure (defined as CSF WBC >20 cells/μL at Month 18 and/or signs and symptoms evoking a relapse at Month 18); or a CSF WBC >20 cells/μL at Month 18. This outcome was analyzed using a Kaplan-Meier approach to estimate the cumulative rate of proven and definitive failures. The proven failure-free probability was estimated as an alternative (more liberal) success rate (95% CI) at Month 18 based on the Kaplan-Meier estimate of the rate of participants who were not proven failures	18 months post-dose
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Occurrence of any AEs, during the observation period and until 6 months post-dose (for non-serious AEs) and until 18 months post-dose for SAEs. Analysis of AEs was based on the concept of TEAEs, defined as any AEs occurring on or after the date of study-drug administration or worsening in intensity on or after the date of study-drug administration.	From the single dose acoziborole administration until 6 months post-dose for non-serious AEs and 18 months post-dose for serious AEs
Number of Participants With Serious TEAEs	Occurrence of any serious TEAEs during the observation period and until 18 months post-dose.	From the single dose acoziborole administration until 18 months post-dose
Acoziborole Area Under the Curve From Time Zero to 240 Hours Post Dose (AUC0-240h) in Whole Blood Considering Concentration-time Data up to 240 Hours After a Single Administration	Participants received a single dose of 960 mg acoziborole on Day 1. Acoziborole in whole blood was assessed pre-dose and 4, 9, 24, 48, 72, 96, and 240 hours after the single administration, (on Days 1, 2, 3, 4, 5, and 11). Data up to 240 hours post dose were considered for this analysis. Descriptive statistics of the AUC0-240h were presented. The activity of acoziborole is more exposure-dependent than concentration-dependent, therefore the exposure (AUC) was used as the main PK data for efficacy purposes.	Pre-dose and 4, 9, 24, 48, 72, 96, and 240 hours post-dose
Mean Acoziborole Concentration in CSF After 240 Hours in Participants With Late-stage HAT	Participants received a single dose of 960 mg acoziborole on Day 1. Acoziborole in CSF of participants with late-stage HAT was assessed 240 hours after the single administration (on Day 11). Descriptive statistics of the acoziborole concentration were presented.	240 hours post-dose
Mean Acoziborole Concentration in CSF After 240 Hours in Participants With Early- and Intermediate-stage HAT	Participants received a single dose of 960 mg acoziborole on Day 1. Acoziborole in CSF of participants with early- and intermediate-stage HAT was assessed 240 hours after the single administration (on Day 11). Descriptive statistics of the acoziborole concentration were presented.	240 hours post-dose

Collaborators and Investigators

• Sponsor: Drugs for Neglected Diseases
• Collaborators: Bill and Melinda Gates Foundation
• Investigators: Principal Investigator: Victor Kande Betu Kumeso, Dr, Ministère de la Santé, The Democratic Republic of the Congo

Publications and helpful links

General Publications

• Betu Kumeso VK, Kalonji WM, Rembry S, Valverde Mordt O, Ngolo Tete D, Pretre A, Delhomme S, Ilunga Wa Kyhi M, Camara M, Catusse J, Schneitter S, Nusbaumer M, Mwamba Miaka E, Mahenzi Mbembo H, Makaya Mayawula J, Layba Camara M, Akwaso Massa F, Kaninda Badibabi L, Kasongo Bonama A, Kavunga Lukula P, Mutanda Kalonji S, Mariero Philemon P, Mokilifi Nganyonyi R, Embana Mankiara H, Asuka Akongo Nguba A, Kobo Muanza V, Mulenge Nasandhel E, Fifi Nzeza Bambuwu A, Scherrer B, Strub-Wourgaft N, Tarral A. Efficacy and safety of acoziborole in patients with human African trypanosomiasis caused by Trypanosoma brucei gambiense: a multicentre, open-label, single-arm, phase 2/3 trial. Lancet Infect Dis. 2023 Apr;23(4):463-470. doi: 10.1016/S1473-3099(22)00660-0. Epub 2022 Nov 29.

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2016
• Primary Completion (Actual): September 8, 2020
• Study Completion (Actual): September 8, 2020

Study Registration Dates

• First Submitted: March 7, 2017
• First Submitted That Met QC Criteria: March 16, 2017
• First Posted (Actual): March 23, 2017

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: August 28, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vector Borne Diseases; Infections; Protozoan Infections; Parasitic Diseases; Euglenozoa Infections; Trypanosomiasis; Trypanosomiasis, African; SCYX 7158
• Other Study ID Numbers: DNDi-OXA-02-HAT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data underlying the results of this study are available upon request because they contain potentially sensitive personal information, which must be de-identified at the individual level. Interested researchers may request access to de-identified participant data from Vivli, the data-sharing partner of the DNDi, commissioner of this study, at https://vivli.org/ourmember/dndi/.
• IPD Sharing Time Frame: Available upon request (see above)
• IPD Sharing Access Criteria: Available upon request (see above)
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No