Real World Evaluation of an Albendazole-Ivermectin Coformulation Safety and Effectiveness

ConditionSoil-Transmitted Helminths

Trial statusRecruiting

Trial phasePhase 3

Trial typeInterventional

Biological sexAll

Age5-17

SponsorInsud Pharma

About this trial

An open-label, randomized by school, two-arm pragmatic trial, will be conducted involving two study sites in Sub-Saharan-Africa (SSA), Ghana and Kenya, to evaluate safety and effectiveness of the newly developed fixed dose combination (FDC) of albendazole (ALB) and ivermectin (IVM) as a single dose to treat Soil-Transmitted Helminths (STH), compared to the standard dose ALB single dose for the treatment and control of STH (REALISE study: Real World Evaluation of an Albendazole-Ivermectin Coformulation Safety and Effectiveness). The general objectives are to validate the benefits of FDC through this pragmatic trial in a context of mass drug administration (MDA) programme to evaluate the safety as a primary endpoint and effectiveness profile as a secondary endpoint, in a large population of school-aged children.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Age: 5 to 17 years old (included).

Height: over 110 cm.

Parental acceptance to participate in the study by obtaining written informed consent approved by the Ethics Committee. Written assent will also be obtained from children according to the local national legislation (12-17 years old).

Disqualifiers

Epidemiological risk of being infected by Loa loa, defined as those who have visited any of the following countries: Angola, Cameroon, Central Africa Republic, Chad, Congo, Democratic Republic of the Congo, Equatorial Guinea, Ethiopia, Gabon, Nigeria and Sudan.

Serious medical illness, defined as participants showing symptoms of acute illness which could hamper the participation in the trial, such as high-grade fever, severe diarrhoea, neurological symptoms or others, per investigator's criteria.

Any condition prevents the appropriate evaluation and follow-up of the participant, per the investigator's criteria.

Known hypersensitivity to any component of either study treatment.

Trial design

Design model

Parallel

Treatments tested in this trial

Pre-screening Phase
Drug
The entire school population will be invited to participate in the study. The purpose of this phase is to confirm participant eligibility for enrolment in the study based on the inclusion and exclusion criteria. Given the context in which the clinical trial is being conducted, in many instances, group meetings with the parents/guardians of potential participants in the community or at school might be necessary as part of the informed consent process. This consent process may be performed up to three months before the start of the screening visit activities. Participants and parents/guardians of subjects will be asked to confirm in writing their agreement to participate in the trial before any study-specific procedure is conducted. In addition, written assent will be sought for participants over 12 years of age.
Screenig Phase
Drug
The purpose of the screening visit is to confirm subject eligibility for enrolment in the study based on the inclusion/exclusion criteria. Screening visits in a particular school can be performed between 14 and 7 days before the intervention (Day 0). To continue with the screening activities, participants must have signed written consent from their parent or legal guardian, and in the case of participants aged 12 years or older, they must also have a signed assent form before any specific study procedure is performed.If the consent/assent process has not been finalized during the pre-screening phase, this can be completed during the screening visit, but always before any trial procedure. All participants who consent to participate in the trial will be given a Participant Screening Number, which will be assigned sequentially as the informed and assent forms are signed.
Randomization
Drug
Only when the screening process is finalized in a particular school, and the list of eligible participants is closed, with at least 100 eligible participants, will the school be a candidate for randomization. Once the screening process is finalized, the investigator or designee will notify the ISGlobal Trial Statistician, who will provide the School Randomization ID allocated based on the randomization lists created before the trial starts. School Randomization ID will be assigned sequentially per site, following the order of school randomization. Additionally, the ISGlobal Trial Statistician will provide the site with the list of eligible participants per school randomly selected to participate in the Effectiveness Cohort.
Baseline Effectiveness Cohort
Drug
Before the administration of the study drug at school, participants selected for the Effectiveness Cohort will perform an additional study visit during which they will provide the study team with a stool sample for STH analysis. A dried blood spot (DBS) sample will also be taken to test for S. stercoralis. Sampling of the baseline effectiveness cohort will be conducted within 7 days before the start of the school study intervention. In addition to the delivery of the stool/blood sample, participants from the effectiveness cohort will be evaluated for scabies by designated study personnel following the IACs simplified criteria.
Day 0 Trial Intervention
Drug
Within seven days after the first sample for the baseline effectiveness cohort is collected, the school's mass administration of the allocated drug will take place. All participants included in the list of eligible subjects from a particular randomized school will receive a single dose of the medication administered to their school (FDC or ALB). Before the administration, participants will be asked about any medical condition that has arisen since the last study visit, in which case information will be documented as a concomitant disease. In case a participant vomits within one hour after the study drug intake (during the study physician observation period), the participant will continue participating in the trial and may still participate in the effectiveness cohort. If they are chosen for the day 21 or month 11 effectiveness cohort, an additional sensitivity analysis will be performed without including these participants, considered as Intervention Fail.
Active Surveillance (study visit Day 1, Day 2 and Day 7)
Drug
Active safety surveillance will be performed at school during the trial intervention on day 0 until day 7 post-intervention. The assessment will include recording of all AEs and SAEs presented by study participants from the intake of the study drugs, and for two additional days (Day 1 and Day 2 study visits). During active surveillance, participants will be visited by a study physician at school during the study intervention, on day one and day two, and they will be questioned about any potential AE or change in a pre-existing condition. In addition, a final safety visit will be conducted to all participants at Day 7 to collect data on any potential AE occurred between day 2 and the end of the surveillance period and to perform a follow up of any AE ongoing after Day 2 visit.
Passive Surveillance
Drug
Passive surveillance will be carried out by monitoring AEs in health facilities near the schools involved in the study for six days after the intervention until Day 7 (end of the safety surveillance period). Although AE will be actively monitored during the scheduled study visits, this passive surveillance will allow for the identification of AEs and potential SAEs that might occur and remained underreported in case the participant does not attend school during the active safety surveillance period. In addition, a diary cards will be given to participants to write any AE they may have from Day 2 to Day 6 post intervention.
Post-Treatment Effectiveness Evaluation
Drug
Post-treatment effectiveness evaluation will be performed by measuring the prevalence of STH at two time points: 21 days after the intervention (± 7 days) and 11 months after intervention (± 28 days). Additionally, the reduction in S. stercoralis seroprevalence will be evaluated 11 months after the intervention. These participants will be tested for STH by Kato-Katz at the two post-treatment time points (day 21 and month 11) and for S. stercoralis by NIE ELISA at 11 months. The diagnostic test will be the same as in the intervention of Baseline Effectiveness Cohort. As part of the genetic monitoring pilot study and the microbiome analysis, the same samples will be collected as described in the intervection of Baseline Effectiveness Cohort.

Treatment groups

20,000 Participants

are divided into 2 treatment groups

Group A: Fixed Dose Combination (FDC) albendazole and Ivermectin (ALB/IVM )Experimental treatment 8 interventions

Group B: Albendazole (ALB)Active comparator 8 interventions

Trial outcomes

Primary outcomes

AEs and SAEs record of participants treated with FDC compared to ALB.

Adverse events will be recorded in the source documents and the electronic Case Report Form during the trial. The nature of the AE, its date and time of onset, duration and severity, therapy employed (only for SAEs) and the investigator's opinion of causality to the study drug with an alternate aetiology, if appropriate, will be documented. Changes in the severity of an AE will be documented to allow an assessment of the duration of the event at each level of intensity. Classification of the AEs and SAEs according to their frequency will be performed by the Sponsor at the end of the trial.

Time frame

7 days, active surveillance (Day 0 (1 hour), Day 1, Day 2 and Day 7 post-intervention) and passive surveillance (From Day 0 up to Day 6 post-intervention)

Secondary outcomes

Reduction in T. trichiura prevalence in participants treated with FDC compared with ALB.

At each time point, one stool sample will be requested from each selected participant, and the presence and number of STH eggs will be determined by a single Kato Katz method (WHO gold standard for STH diagnosis) using microscopy. T. trichiura prevalence will be considered as the number of participants infected divided by the total number of participants in the effectiveness cohort. STH diagnosis by Kato-Katz on fresh stool (samples analysed up to a maximum of 24 hours after sample collection). The stool sample will be analysed in the local laboratory to estimate STH prevalence at baseline in each school as part of evaluating the STH effectiveness of the treatment arms.

Time frame

Baseline, 21 days and 11 months post-intervention

Other outcomes

Exploratory 1: Reduction in Strongyloides stercoralis seroprevalence in participants treated with FDC compared with ALB.

A dried blood spot (DBS) will be obtained from the selected effectiveness cohort at each time point. The presence of specific antibodies against S. stercoralis will be determined by standard serology methods (ELISA). The seroprevalence of S. stercoralis will be calculated as the number of participants with a positive result by serology divided by the total number of participants in the effectiveness cohort. For the ELISA assay based on the recombinant S. stercoralis NIE antigen, a few drops of blood will be taken from the participants using Dried blood spot testing (DBS) to estimate the baseline prevalence of S. stercoralis.

Time frame

Baseline and 11 months

Exploratory 2: Reduction in hookworms prevalence in participants treated with FDC compared with ALB.

At each time point, one stool sample will be requested from each selected participant, and the presence and number of STH eggs will be determined by a single Kato Katz method (WHO gold standard for STH diagnosis) using microscopy. Hookworms prevalence will be considered as the number of participants infected and divided by the total number of participants in the effectiveness cohort. STH diagnosis by Kato-Katz on fresh stool (samples analysed up to a maximum of 24 hours after sample collection). The stool sample will be analysed in the local laboratory to estimate STH prevalence at baseline in each school as part of evaluating the STH effectiveness of the treatment arms.

Time frame

Baseline, 21 days and 11 months post-intervention

Exploratory 3: Reduction in A. lumbricoides prevalence in participants treated with FDC compared with ALB.

At each time point, one stool sample will be requested from each selected participant, and the presence and number of STH eggs will be determined by a single Kato Katz method (WHO gold standard for STH diagnosis) using microscopy. A.lumbricoides prevalence will be considered as the number of participants infected and divided by the total number of participants in the effectiveness cohort. STH diagnosis by Kato-Katz on fresh stool (samples analysed up to a maximum of 24 hours after sample collection). The stool sample will be analysed in the local laboratory to estimate STH prevalence at baseline in each school as part of evaluating the STH effectiveness of the treatment arms.

Time frame

Baseline, 21 days and 11 months post-intervention

Exploratory 4: Describe the frequency of scabies before and after the intervention in the two treatment arms.

Frequency of scabies measured by IACS simplified criteria. The frequency of scabies will be calculated as the number of participants infected divided by the total number of participants in the effectiveness cohort.

Time frame

Baseline and 21days

Sponsors and contacts

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Insud Pharma

Lead sponsor

Ghana Health Services

Collaborator

Kenya Medical Research Institute

Collaborator

Bridges to Development

Collaborator

Sanger Institute

Collaborator

Barcelona Institute for Global Health

Collaborator

European Union

Collaborator

Swiss Confederation

Collaborator

Fundación Mundo Sano

Collaborator

Source ClinicalTrials.gov

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