Human African TrypanosomiasisPhase 3STROgHATNCT06356974
Stop Transmission of Gambiense Human African Trypanosomiasis (STROgHAT)
A Phase 3 study testing Treatment of seropositive individuals (positive serology test, but parasitology not confirmed) in people with Human African Trypanosomiasis, run by Drugs for Neglected Diseases.
Trial 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… Read more about this study
- Who is it for?
- Ages 11 years and older
- Conditions the study is for
- Human African Trypanosomiasis
- What is being tested?
- Treatment of seropositive individuals (positive serology test, but parasitology not confirmed)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,500 participants
- Where
- No sites listed yet
- Study dates
- 8 Apr 2024to 30 Dec 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 11 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- • 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
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- 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.
Who cannot join
- • 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)
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: An Intervention Study to Evaluate the Impact of Treating gHAT Seropositive Subjects With Acoziborole on Transmission of T.b. Gambiense, and Obtain Further Safety Data on Acoziborole in gHAT Seropositive Individuals
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.
Read the 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
- Being tested
- Treatment of seropositive individuals (positive serology test, but parasitology not confirmed)
- Keywords
- acoziborole, elimination of transmission, seropositive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treatment of seropositive individuals (positive serology test, but parasitology not confirmed)Drug
Also called Acoziborole
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Treatment of seropositive individuals (positive serology test, but parasitology not confirmed) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 3 years
Secondary outcomes (2)
Economic evaluation
Cost data will be gathered throughout the study and used to perform an economic evaluation of the screen \& treat strategy in the study area. A separate analysis plan will be developed. The investigators will cost the strategy using a health-care provider's perspective, focusing on costs incurred by the Ministry of Health (PNLTHA and INRB) and donors. Only costs related to the STROGHAT elimination strategy will be considered, research and management costs will be excluded. A mixed costing methodology will be used to estimate financial and economic costs. Recurrent and capital costs will be considered. The sensitivity analysis will use discount rates of 0%, 5% and 10% and evaluate the impact of the main cost drivers. The cost information collected will also be used to develop a tool to support national programs estimate the cost and budget necessary if they would like to implement a similar intervention in a different context if the trial shows promising results.
Measured: 4 years
assessment of the performance of several diagnostic tests
The specificity of the diagnostic tests used in the study: CATT and RDTs in the field, and ELISA/T.b. gambiense, immune trypanolysis and Trypanozoon-RT-PCR multiplex at INRB level, will be evaluated. The reference standard will be parasitological confirmation. The specificity of the different tests will be calculated by measuring the number of index tests négatives over the number of index test négatives plus index test positives tesing negative with the reference test.
Senstivity will not be calculated as in the context of low prevalence, only few positives are detected not allowing for statistical inference.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2024
- Study start8 Apr 2024 (estimated)
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Human African TrypanosomiasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- one-arm, open label, non-randomized, multicentre, phase IIIb study
- Masking
- None (open label)
- Enrolment
- 2,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Drugs for Neglected Diseases
- Sponsor type
- University, hospital or other
- Collaborators
- Institute of Tropical Medicine, Belgium, Institut de Recherche pour le Developpement, Institut National de Recherche Biomedicale (INRB), Ministry of Public Health, Democratic Republic of the Congo
- Responsible party
- Sponsor
- Investigators
- Elena Nicco, MD, Study director, Institute of Tropical Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06356974
- Sponsor's protocol ID
- STROgHAT
- Acronym
- STROgHAT
- Status last verified
- Apr 2024
- First submitted
- 29 Mar 2024
- Last updated
- 10 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: anonymity of participants must be guaranteed, GDRPR rules will apply anonymised study results can be shared with other researchers upon request
Publications
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.
PubMed 15117297Dickie 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.
PubMed 32092897Simarro 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.
PubMed 23145192Ngay 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.
PubMed 34534223Van 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.
PubMed 34695154Simarro 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.
PubMed 1934239Buscher 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.
PubMed 25103304Camara 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.
PubMed 36941656Compaore 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.
PubMed 35543528Nicco 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.
PubMed 40191624