NCT06282315

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

A Pragmatic Phase III Multicentre Clinical Trial to Evaluate the Safety and Effectiveness of a Single Dose of an Albendazole-Ivermectin Coformulation vs Albendazole for Preventive Chemotherapy of Soil-Transmitted Helminth Infections in School-Aged Children

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 20,000 (estimated)
• Sponsor: Insud Pharma · Industry
• Sex: All
• Age: 5 Years – 17 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed description

In the REALISE study a total of 20,000 children will be enrolled approximately in both countries for the safety cohort, 10,000 children in around 30 schools per country (5,000 per treatment arm). For the effectiveness cohort, REALISE study is planned to assess a total of approximately 4,500 participants in both countries, 2,250 children per country (75 children for each of the 30 schools and 1,125 children per treatment arm). The REALISE study will have two study arms: * Treatment arm 1: Single dose of a tablet of FDC 400 mg/18 mg IVM or 400 mg ALB/9 mg IVM, administered according to the following age criteria: 1. For children from 5-14 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/9 mg IVM. 2. For children from 15-17 years old (included) at the time of screening visit: 1 tablet of FDC 400 mg ALB/18 mg IVM. * Treatment arm 2: Single dose of a tablet of ALB 400 mg (active control arm). Randomization will occur at the school level, and each eligible participant within a school will receive only one of the study treatments. Given the variable number of children in the Ghanaian and Kenyan schools, and that conducting the intervention for only a fraction of the school is not feasible, it may be possible to exceed the intended trial sample size. Efforts will be made to minimize this The Primary objective of the trial will be to evaluate and compare safety of a FDC against ALB alone via MDA in two study areas in Kenya and Ghana in the seven days after first treatment intervention. Thus, as a primary outcome, the adverse effects will be monitored through a specific surveillance system established in schools, hospitals and health centers as health facilities. Safety surveillance will be performed for seven days after each MDA, allowing for the identification of AEs and SAEs in subpopulations (in terms of gender, age, body weight, comorbidities, and additional risk factors) for better estimation of safety. This surveillance will consist of active surveillance at day 0, day 1, day 2 and day 7 post-intervention to record any AEs and SAEs presented by participants during the conducting study with drug intake. In addition, the trial will include passive surveillance monitoring AEs and SAEs through diary cards given to the subjects, and in hospitals and health centres near the schools involved in the study for six days after the intervention until day 7 (end of the safety surveillance period) to avoid the loss of possible AEs and SAEs underreported, in case the participant does not attend school during the surveillance period. The Secondary objective will be to evaluate the effectiveness of one round of MDA with FDC compared to ALB against STH T. trichiura by microscopy, to address the reduction of the prevalence of this species in the FDC and ALB arms. Thus, the secondary outcome will be measured at the school level, prior to the first intervention (baseline), at 21 days post intervention and within the month prior to the second yearly intervention which is at s11 months. Moreover, the trial will include Exploratory objectives to evaluate the effectiveness of one round of MDA with FDC compared to ALB against S. Stercolaris by serology to address the outcome of the seroprevalence reduction of this species in the FDC arm and ALB arm and to evaluate the effectiveness of one round of MDA with FDC compared with ALB against Hookworms and A. lumbricoides to determine the reduction of the prevalence of these species through microscopy. The frequency of scabies also will be measured as an exploratory objective in the effectiveness cohort at baseline and 21 days after the intervention. Genetic monitoring is an exploratory objective to address the impact of the two treatment arms on the genetic structure of the populations of parasites. This genetic analysis will measure on the one hand the genetic diversity as an estimation of the effective population size and a proxy for successful control programmes, as seen for other parasites (it is expected that diversity will be lower in populations closed to elimination. In addition, the genetic differentiation between baseline parasites and the parasites collected after the interventions will be evaluated. Thus, the investigators will be able to evaluate the impact of both treatments in genetic selection and potentially identify genes associated with treatment failure and anthelmintic resistance. On the other hand, the investigators will measure the genome-wide association to see the relationship between parasite genetics and parasite clearance in response to treatments. As part of the exploratory endpoints, the investigators will estimate alpha and beta diversity as well as the composition of the microbiome at phylum, family and genus level for each sample and time point. Investigators will assess differences between infected and uninfected participants at baseline by comparing the diversity and relative abundance of the different bacteria between baseline and 21 days after the intervention, comparing the effect of the two treatment arms in the microbiome composition. Moreover, the investigators will also explore the recovering of the initial microbiome composition between month 11 post-intervention and baseline, particularly in those participants that were not newly infected after 11 months.

Conditions

• Soil-Transmitted Helminths

Interventions

Type	Name	Description
DRUG	Pre-screening Phase	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.
DRUG	Screenig Phase	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.
DRUG	Randomization	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.
DRUG	Baseline Effectiveness Cohort	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.
DRUG	Day 0 Trial Intervention	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.
DRUG	Active Surveillance (study visit Day 1, Day 2 and Day 7)	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.
DRUG	Passive Surveillance	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.
DRUG	Post-Treatment Effectiveness Evaluation	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.

Timeline

• Start date: 2025-09-01
• Primary completion: 2026-04-01
• Completion: 2027-02-01
• First posted: 2024-02-28
• Last updated: 2025-09-15

Locations

2 sites across 2 countries: Ghana, Kenya