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

NCT03087955 | Completed Phase 2 Results DMC

• 1 other identifier: DNDi-OXA-02-HAT
• Study Type: interventional
• Target: 208
• Locations: 2 countries
• Sites: 12

Brief Summary

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.

Conditions

Trypanosomiasis, African; Gambiense Trypanosomiasis; Sleeping Sickness

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Percentage of Participants With Late-stage HAT Whose Treatment Outcome Was a Success at Month 12 According to Adapted WHO Criteria

  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

  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

  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

  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

  6 months post-dose

Study Arms (2)

Late-stage HAT

EXPERIMENTAL

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

Early- and intermediate-stage HAT

EXPERIMENTAL

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

Interventions

Acoziborole DRUG

Acoziborole 3 x 320 mg tablets (fasted state)

Also known as: SCYX-7158

Early- and intermediate-stage HAT; Late-stage HAT

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patient
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead
• Bill and Melinda Gates Foundation: collaborator

Study Sites (12)

Centre de Traitement de Nkara

Nkara, Bandundu, Democratic Republic of the Congo

Location

Centre de Traitement de Kimpese

Kimpese, Bas-Congo Province, Democratic Republic of the Congo

Location

Hôpital Général de Référence de Ngandajika

Gandajika, East Kasai, Democratic Republic of the Congo

Location

Hôpital Secondaire de Katanda

Katanda, East Kasai, Democratic Republic of the Congo

Location

Hôpital de Dipumba

Mbuji-Mayi, East Kasai, Democratic Republic of the Congo

Location

Hôpital Général de Référence de Bagata

Bagata, Kwilu, Democratic Republic of the Congo

Location

Hôpital Général de Référence de Masi-Manimba

Masi-Manimba, Kwilu, Democratic Republic of the Congo

Location

Hôpital Général de Référence de Kwamouth

Kwamouth, Mai Ndombe, Democratic Republic of the Congo

Location

Hopital Général de Réference de Bandundu

Bandundu Province, Democratic Republic of the Congo

Location

Hôpital de Référence d'Isangi

Isangi, Democratic Republic of the Congo

Location

Hôpital Général de Référence Roi Baudouin

Kinshasa, Democratic Republic of the Congo

Location

Centre de Traitement de la THA de Dubreka

Dubréka, Dubreka, Guinea

Location

Related Publications (1)

• 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.

  PMID: 36460027 RESULT

MeSH Terms

Conditions

Trypanosomiasis, African

Interventions

SCYX 7158

Condition Hierarchy (Ancestors)

Trypanosomiasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases

Limitations and Caveats

The principal limitation of this study was the lack of comparator or control group, instead comparisons were made with a yardstick based on historical data. The sample size was based on the maximum feasible enrolment within a reasonable timeframe, because of the challenges of enrolling patients with HAT in clinical trials given the drastic decline in prevalence, and in order to expose as many participants to the test drug as possible.

Results Point of Contact

• Title: Sandra Rembry, PharmD
• Organization: Drugs for Neglected Diseases

srembry@dndi.org

+41229077734

Study Officials

• Victor Kande Betu Kumeso, Dr

  Ministère de la Santé, The Democratic Republic of the Congo

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2017
• First Posted: March 23, 2017
• Study Start: October 11, 2016
• Primary Completion: September 8, 2020
• Study Completion: September 8, 2020
• Last Updated: September 17, 2025
• Results First Posted: September 17, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Available upon request (see above)
• Access Criteria: Available upon request (see above)

Locations

DE (11); GU (1)