Stop Transmission of Gambiense Human African Trypanosomiasis (STROgHAT)

NCT ID: NCT06356974

Last Updated: 2024-04-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 2500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-08
• Study Completion Date: 2027-12-30

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.

Detailed Description

Recently acoziborole, a non-toxic single dose oral drug for gHAT, has passed phase 3 evaluation in adult patients. This drug is envisioned to be used to treat gHAT irrespective of disease stage, thus rendering the lumbar puncture for stage determination redundant. Having available a single dose oral treatment with limited risk of toxicity opens up new perspectives for eliminating the disease. Treating anyone testing positive to a serological screening test, without further need for on the spot parasitological confirmation and stage determination, will greatly simplify procedures in the field, avoid missing many cases, has the potential to increase uptake of screening and may thus even curb transmission of the causative parasite, which is assumed to have only a human reservoir.

Although this innovative option for gHAT control is now feasible, its true effectiveness and cost effectiveness for curtailing transmission remain to be determined.

The current gHAT control strategy is based on active screening of people living in villages at risk for gHAT by mobile screening teams. All villages from which gHAT cases were reported are screened for three years in a row until no further cases are found. They are then screened once more, two years after the last case was reported. If no further cases are found, transmission is assumed to have been interrupted. However, it has also previously been shown estimated that up to 50% of prevalent cases are not detected or not cured, with major losses occurring during the parasitological confirmation step. Other important barriers are the fear of the lumbar puncture required for stage determination and of toxicity of treatment, in particular associated with melarsoprol, no longer in use for gHAT, but still well-known especially by the elder population. Even if up to 50% of prevalent gHAT cases were not treated, the epidemiological data shows that the disease is on the decline. This may however be insufficient to achieve complete elimination of transmission. 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. Bearing in mind that acoziborole has not yet been registered and that 'screen & treat' has not yet been adopted as the new policy, the investigators will for the duration of this study continue performing parasitological confirmation on the spot and treat anyone confirmed by parasitology with standard of care. Any serological suspect not confirmed by parasitology on the spot will be offered treatment with acoziborole (study Part B), conditional on a set of inclusion and exclusion criteria If acoziborole allows the investigators to implement a screen & treat strategy, allowing to detect and treat all g-HAT prevalent cases, and possibly in the future without the limitations of cumbersome diagnostic confirmation on the spot, the investigators expect that elimination of transmission is also possible in a mainland focus. Implementing such a study under relatively well controlled conditions will also allow gathering further evidence on safety of acoziborole, before a screen & treat strategy is rolled out on a larger scale. In addition it will provide information on the cost of such a strategy and on some essential parameters of the tests utilized.

Conditions

Human African Trypanosomiasis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment of seropositives

• 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

Group Type: EXPERIMENTAL

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

Intervention Type: 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.

Interventions

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

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.

Intervention Type: DRUG

Other Intervention Names

Acoziborole

Eligibility Criteria

Inclusion Criteria

• • 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
• 11 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.

Exclusion Criteria

• • 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)

• Minimum Eligible Age: 11 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Tropical Medicine, Belgium

OTHER

Sponsor Role: collaborator

Institut de Recherche pour le Developpement

OTHER_GOV

Sponsor Role: collaborator

Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo

OTHER

Sponsor Role: collaborator

Ministry of Public Health, Democratic Republic of the Congo

OTHER_GOV

Sponsor Role: collaborator

Drugs for Neglected Diseases

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elena Nicco, MD

Role: STUDY_DIRECTOR

Institute of Tropical Medicine

Central Contacts

Elena Nicco, MD

Role: CONTACT

enicco@itg.be

+3232476497

Digas NGOLO TETE, MPH

Role: CONTACT

dngolo@dndi.org

+243813180161

References

Robays J, Bilengue MM, Van der Stuyft P, Boelaert M. The effectiveness of active population screening and treatment for sleeping sickness control in the Democratic Republic of Congo. Trop Med Int Health. 2004 May;9(5):542-50. doi: 10.1111/j.1365-3156.2004.01240.x.

Reference Type: BACKGROUND

PMID: 15117297 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32092897 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23145192 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34534223 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34695154 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 1934239 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25103304 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 36941656 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35543528 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 40191624 (View on PubMed)

Other Identifiers

STROgHAT

Identifier Type: -

Identifier Source: org_study_id