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

"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."

"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."

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.

"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."

"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 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 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 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."