Stop Transmission of Gambiense Human African Trypanosomiasis (STROgHAT) (STROgHAT)

April 4, 2024 updated by: Drugs for Neglected Diseases

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

2500

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Elena Nicco, MD
  • Phone Number: +3232476497
  • Email: enicco@itg.be

Study Contact Backup

  • Name: Digas NGOLO TETE, MPH
  • Phone Number: +243813180161
  • Email: dngolo@dndi.org

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Drug: 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.
Other Names:
  • Acoziborole

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Interruption of transmission of T.b. gambiense
Time Frame: 4 years

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
Time Frame: 3 years

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Economic evaluation
Time Frame: 4 years
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.
4 years
assessment of the performance of several diagnostic tests
Time Frame: 4 years

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.
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Drugs for Neglected Diseases

Collaborators

Institute of Tropical Medicine, Belgium
Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo
Institut de Recherche pour le Developpement
Ministry of Public Health, Democratic Republic of the Congo

Investigators

  • Study Director: Elena Nicco, MD, Institute of Tropical Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 8, 2024

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

December 30, 2027

Study Registration Dates

First Submitted

March 29, 2024

First Submitted That Met QC Criteria

April 4, 2024

First Posted (Actual)

April 10, 2024

Study Record Updates

Last Update Posted (Actual)

April 10, 2024

Last Update Submitted That Met QC Criteria

April 4, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STROgHAT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

anonymity of participants must be guaranteed, GDRPR rules will apply anonymised study results can be shared with other researchers upon request

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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