Stop Transmission of Gambiense Human African Trypanosomiasis (STROgHAT)

NCT06356974 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: STROgHAT
• Study Type: interventional
• Target: 2,500
• Locations: 0 countries
• Sites: N/A

Brief Summary

This protocol describes both the epidemiological study which aims at assessing whether over a three-year period a zero prevalence can be achieved when implementing a screen \& treat approach with acoziborole, as well as a nested clinical study aimed at generating further evidence on safety of acoziborole in gambiense human African trypanosomiasis (gHAT) seropositives individuals. The overall coordinator will be ITM. ITM will be fully responsible for the epidemiological study (study Part A), including cost effectiveness and evaluation of diagnostic tests. DNDi will be the legal sponsor of the nested safety clinical study (study Part B) and will ensure compliance with regulatory requirements and good clinical practices (GCP) for this part of the study. The investigators hypothesize that by systematically screening the populations of all endemic villages in a well-defined HAT focus and by expanding gHAT treatment to all seropositives, that it will be able to arrive at a zero prevalence over a three-year period. The objectives are to evaluate whether a strategy based on widened treatment for all parasitologically negative seropositive gHAT suspects with acoziborole can lead to interruption of transmission of T.b.gambiense in a mainland focus and to assess the safety of acoziborole in gHAT seropositve individuals and parasitologically negative.

Conditions

Human African Trypanosomiasis

Keywords

acoziborole, elimination of transmission, seropositive

Outcome Measures

Primary Outcomes (2)

• Interruption of transmission of T.b. gambiense

  to evaluate whether a strategy based on widened treatment for all parasitologically negative seropositive gHAT suspects with Acoziborole can lead to interruption of transmission of HAT in a mainland focus The HAT prevalence with 95%CI will be calculated using the data from active and passive screening campaigns during year 1,2,3 of the project. Participation rate to the screening activities per age group and sex will also be calculated during the study period. The primary endpoint is the prevalence of confirmed HAT cases, either at point of care by parasitological tests or at the reference laboratory by a positive immunological test (ELISA/T.b.gambiense or trypanolyisi) AND a positive molecular test (18S rRNA or q177T). This prevalence will be determined among the population screened during the fourth and final survey round.

  4 years

• Assessment of safety

  Proportion of participants who present related treatment emergent severe adverse events (severe related TEAEs) Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) SOC and PT. The primary endpoint for this study is the occurrence of severe related TEAEs from administration of study drug up to 3 months post-treatment. It is a binary endpoint (presence or absence of severe TEAE). Other safety endpoints will be collected and analyzed in the same manner as the primary endpoints. * Proportion of participants with mild or moderate related TEAES * Proportion of participants with any (mild, moderate, severe) TEAES * Proportion of participants with serious treatment emergent adverse events (TESAEs) from time of first administration

  3 years

Secondary Outcomes (2)

• Economic evaluation

  4 years

• assessment of the performance of several diagnostic tests

  4 years

Study Arms (1)

Treatment of seropositives

EXPERIMENTAL

* acoziborole three 320-mg tablets (960 mg dose), administered by the oral route to adolescent and adults ≥15 years as single dosing regimen on Day 1 of the study in fed or fasting state * acoziborole two 320-mg tablets (640 mg dose), administered by the oral route to children 11-14 years (and ≥30kg) as single dosing regimen on Day 1 of the study in fed or fasting state No active comparative treatment will be used in this study Doses and treatment regimens * Adolescent and adults ≥15 years: 960 mg (3x320mg) oral unique dose in fed or fasting state * Children 11-14 years (and ≥30kg): 640 mg (2x320mg) oral unique dose in fed or fasting state

Drug: Treatment of seropositive individuals (positive serology test, but parasitology not confirmed)

Interventions

Treatment of seropositive individuals (positive serology test, but parasitology not confirmed) DRUG

Subjects agreeing to participate in the study and matching the inclusion/exclusion criteria will receive acoziborole 960 or 640 mg in a single intake at study day 1. Following treatment, participants will attend follow-up visits at home or at the study centre at 3 days and 3-months post treatment.

Also known as: Acoziborole

Treatment of seropositives

Eligibility Criteria

• Age: 11 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants able to give signed informed consent and assent form for adolescents, which includes willingness to comply with the schedule of follow-up visits and other requirements and restrictions listed in the informed consent form (ICF) and in this protocol
• All sexes
• years of age or older at the start of the study and weight ≥30 kg at the screening of Part B
• Participants who are CATT test or HAT RDT positive (information provided by the mobile team and included into TrypElim (see Part A)
• Participants who are able to ingest oral tablets
• Participants with known address and/or contact details provided
• Participants who are able to comply with the schedule of follow-up visits and other requirements of the study
• Participants must agree not take part in any other clinical trials during the participation in part B of this study
• Participants of child-bearing potential must be willing to use appropriate contraceptive methods.

You may not qualify if:

• Individuals with a positive parasitological exam on the spot at baseline (mAECT or lymph gland puncture)
• Participants previously treated for g-HAT or previously treated because of gHAT seropositive results
• Pregnant women
• Breast-feeding women
• Children ≥11 years, but under 30kg body weight at the screening for part B
• Clinically significant medical condition that could, in the opinion of the investigator, jeopardise the subject's safety or participation in the study
• Individuals presenting a jaundice at screening
• Participants who are taking, or who are expected to need to start within 3 months, a medicine (including traditional or herbal) which may interact with acoziborole and which cannot be stopped or adjusted (please refer to investigator manual or contact DNDi)

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead
• Institute of Tropical Medicine, Belgium: collaborator
• Institut de Recherche pour le Developpement: collaborator
• Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo: collaborator
• Ministry of Public Health, Democratic Republic of the Congo: collaborator

Related Publications (10)

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  PMID: 15117297 BACKGROUND

• Dickie EA, Giordani F, Gould MK, Maser P, Burri C, Mottram JC, Rao SPS, Barrett MP. New Drugs for Human African Trypanosomiasis: A Twenty First Century Success Story. Trop Med Infect Dis. 2020 Feb 19;5(1):29. doi: 10.3390/tropicalmed5010029.

  PMID: 32092897 BACKGROUND

• Simarro PP, Cecchi G, Franco JR, Paone M, Diarra A, Ruiz-Postigo JA, Fevre EM, Mattioli RC, Jannin JG. Estimating and mapping the population at risk of sleeping sickness. PLoS Negl Trop Dis. 2012;6(10):e1859. doi: 10.1371/journal.pntd.0001859. Epub 2012 Oct 25.

  PMID: 23145192 BACKGROUND

• Ngay Lukusa I, Van Reet N, Mumba Ngoyi D, Miaka EM, Masumu J, Patient Pyana P, Mutombo W, Ngolo D, Kobo V, Akwaso F, Ilunga M, Kaninda L, Mutanda S, Muamba DM, Valverde Mordt O, Tarral A, Rembry S, Buscher P, Lejon V. Trypanosome SL-RNA detection in blood and cerebrospinal fluid to demonstrate active gambiense human African trypanosomiasis infection. PLoS Negl Trop Dis. 2021 Sep 17;15(9):e0009739. doi: 10.1371/journal.pntd.0009739. eCollection 2021 Sep.

  PMID: 34534223 BACKGROUND

• Van Reet N, Patient Pyana P, Dehou S, Bebronne N, Deborggraeve S, Buscher P. Single nucleotide polymorphisms and copy-number variations in the Trypanosoma brucei repeat (TBR) sequence can be used to enhance amplification and genotyping of Trypanozoon strains. PLoS One. 2021 Oct 25;16(10):e0258711. doi: 10.1371/journal.pone.0258711. eCollection 2021.

  PMID: 34695154 BACKGROUND

• Simarro PP, Sima FO, Mir M, Mateo MJ, Roche J. [Control of human African trypanosomiasis in Luba in equatorial Guinea:evaluation of three methods]. Bull World Health Organ. 1991;69(4):451-7.

  PMID: 1934239 BACKGROUND

• Buscher P, Mertens P, Leclipteux T, Gilleman Q, Jacquet D, Mumba-Ngoyi D, Pyana PP, Boelaert M, Lejon V. Sensitivity and specificity of HAT Sero-K-SeT, a rapid diagnostic test for serodiagnosis of sleeping sickness caused by Trypanosoma brucei gambiense: a case-control study. Lancet Glob Health. 2014 Jun;2(6):e359-63. doi: 10.1016/S2214-109X(14)70203-7. Epub 2014 May 9.

  PMID: 25103304 BACKGROUND

• Camara O, Camara M, Falzon LC, Ilboudo H, Kabore J, Compaore CFA, Fevre EM, Buscher P, Bucheton B, Lejon V. Performance of clinical signs and symptoms, rapid and reference laboratory diagnostic tests for diagnosis of human African trypanosomiasis by passive screening in Guinea: a prospective diagnostic accuracy study. Infect Dis Poverty. 2023 Mar 20;12(1):22. doi: 10.1186/s40249-023-01076-1.

  PMID: 36941656 BACKGROUND

• Compaore CFA, Kabore J, Ilboudo H, Thomas LF, Falzon LC, Bamba M, Sakande H, Kone M, Kaba D, Bougouma C, Adama I, Amathe O, Belem AMG, Fevre EM, Buscher P, Lejon V, Jamonneau V. Monitoring the elimination of gambiense human African trypanosomiasis in the historical focus of Batie, South-West Burkina Faso. Parasite. 2022;29:25. doi: 10.1051/parasite/2022024. Epub 2022 May 11.

  PMID: 35543528 BACKGROUND

• Nicco E, Lejon V, Mwamba Miaka E, Mumba D, Mpanya A, Kambo C, Ngolo D, Mutombo W, Hugonnet S, Rembry S, Tipple C, Inocencio Da Luz R, Snijders R, Vander Kelen C, Roge S, Van Reet N, Tarral A, Verle P, Hasker E. The STROGHAT study protocol: An intervention study to evaluate safety, effectiveness and feasibility of treating gambiense HAT seropositive subjects with acoziborole. Open Res Eur. 2025 Jan 24;5:23. doi: 10.12688/openreseurope.19077.1. eCollection 2025.

  PMID: 40191624 DERIVED

Study Officials

• Elena Nicco, MD

  Institute of Tropical Medicine

  STUDY DIRECTOR

Central Study Contacts

Elena Nicco, MD

CONTACT

+3232476497; enicco@itg.be

Digas NGOLO TETE, MPH

CONTACT

+243813180161; dngolo@dndi.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: one-arm, open label, non-randomized, multicentre, phase IIIb study

Study Record Dates

• First Submitted: March 29, 2024
• First Posted: April 10, 2024
• Study Start: April 8, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027
• Last Updated: April 10, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share