Clinical trial NCT06356974: Stop Transmission of Gambiense Human African Trypanosomiasis (STROgHAT)
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Human African Trypanosomiasis
Keywords: acoziborole, elimination of transmission, seropositive
Lead sponsor: Drugs for Neglected Diseases
Sponsor class: OTHER
Collaborators: name: Institute of Tropical Medicine, Belgium
name: Institut de Recherche pour le Developpement
name: Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo
name: Ministry of Public Health, Democratic Republic of the Congo
First posted: 2024-04-10
Enrollment: 2500
Sex: ALL
Minimum age (years): 11
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: one-arm, open label, non-randomized, multicentre, phase IIIb study
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Interruption of transmission of T.b. gambiense
timeFrame: 4 years
measure: Assessment of safety
timeFrame: 3 years
Secondary outcomes:
measure: Economic evaluation
timeFrame: 4 years
measure: assessment of the performance of several diagnostic tests
timeFrame: 4 years
Other outcomes:
Locations:
Study officials:
affiliation: Institute of Tropical Medicine
name: Elena Nicco, MD
role: STUDY_DIRECTOR
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