A Phase 3 interventional study of Treatment of seropositive individuals (positive serology test, but parasitology not confirmed) in Human African Trypanosomiasis, sponsored by Drugs for Neglected Diseases. Not yet recruiting. Open to participants aged 11 Years and older. Per ClinicalTrials.gov, last updated 2024-04-10.
Sponsored by Drugs for Neglected Diseases · Phase 3, Interventional, and Treatment
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.
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.
26 studies on the registry are indexed under Trypanosomiasis, African; 1 is open to participants now.
This study's planned enrollment of 2,500 is above the median of 155 across 24 interventional studies indexed under Trypanosomiasis, African.
Browse Trypanosomiasis, African studies →Drugs for Neglected Diseases is the lead sponsor of 58 studies on the registry; 3 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Participants able to give signed 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
Exclusion Criteria:
Individuals with a positive parasitological exam on the spot at baseline (mAECT or lymph gland puncture)
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
* 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.
Also known as: Acoziborole
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.
Time frame: 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
Time frame: 3 years
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.
Time frame: 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.
Time frame: 4 years
No study locations are listed for this record.
Plan to share: No — anonymity of participants must be guaranteed, GDRPR rules will apply anonymised study results can be shared with other researchers upon request
Start is estimated for Apr 2024; primary completion for Dec 2026, 32 months later.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Apr 2024. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: SCYX 7158
Drugs for Neglected Diseases