Efficacy, Safety and Acceptability of Ivermectin ODT in PSAC

Hookworm Infections Clinical Trial

— Iverped  

Official title:

Efficacy, Safety and Acceptability of Ascending Doses of Ivermectin in Combination With Albendazole for Trichuris Trichiura Infections in Preschool-aged Children: a Single-blind Randomised Controlled Dose-ranging Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06184399
• Other study ID #: Iverped_1
• Status: Recruiting
• Phase: Phase 2
• Start date: June 5, 2024
• Est. completion date: August 2024

Study information

• Verified date: June 2024
• Source: Swiss Tropical & Public Health Institute
• Contact: Jennifer Keiser, PhD
• Phone: +41 61 284 8218
• Email: jennifer.keiser[@]swisstph.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a single-blind randomized controlled dose-ranging trial aiming at providing evidence on the on the optimal dose of co-administered ivermectin and albendazole in terms of efficacy, safety and acceptability in preschool-aged children (PSAC; aged 2-5 years) infected with whipworm (Trichuris trichiura) on Pemba Island, Tanzania. Additionally, the pharmacokinetics of the newly developed ODTs and the standard ivermectin tablets (Stromectol®) will be compared in this age group.

As measure of efficacy of the treatment the cure rate (percentage of egg-positive participants at baseline who become egg-negative after treatment) will be determined 14-21 days post-treatment.

Description:

This study is a single-blind randomized controlled dose-ranging trial aiming at providing evidence on the optimal dose of co-administered ivermectin and albendazole in terms of efficacy, safety and acceptability in preschool-aged children (PSAC; aged 2-5 years) infected with whipworm (Trichuris trichiura) on Pemba Island, Tanzania. Additionally, the pharmacokinetics of the newly developed ODTs and the standard ivermectin tablets (Stromectol®) will be compared in this age group.

The primary objective of the trial is to comparatively assess the efficacy in terms of cure rate (CR) against T. trichiura infections among PSAC receiving different doses of ivermectin.

The secondary objectives of the trial are to compare the egg reduction rates (ERRs) of the treatment regimens against T. trichiura, to determine the CRs and ERRs of the drugs in study participants co-infected with A. lumbricoides and hookworm, and to evaluate the safety and tolerability of the treatment regimens.

In addition, this study aims to characterize population pharmacokinetics of the ivermectin ODTs compared to standard tablets in T. trichiura infected individuals, and to assess the acceptability of the treatments.

After obtaining informed consent from parents and/or caregivers, the medical history of the participants will be assessed with a standardized questionnaire, in addition to a clinical examination carried out by the study physician before treatment. Enrollment will be based on two stool samples, which will be collected, if possible, on two consecutive days or otherwise within a maximum of 5 days. All stool samples will be examined with duplicated Kato-Katz thick smears by experienced laboratory technicians.

Randomization of participants into the six treatment arms will be stratified according to intensity of infection and age. All participants will be interviewed before treatment, and at 3 and 24 hours and 14-21 days after treatment about the occurrence of adverse events. The efficacy of the treatment will be determined 14-21 days post-treatment by collecting another two stool samples.

The primary analysis will include all participants with primary end point data (available case analysis). Supplementary, a per-protocol analysis will be conducted. CRs will be calculated as the percentage of egg-positive participants at baseline who become egg-negative after treatment. Differences among CRs between treatment arms will be analysed using crude and adjusted logistic regression modeling (adjustment for age, sex and weight). Geometric and arithmetic mean egg counts will be calculated for the different treatment arms before and after treatment to assess the corresponding ERRs. Bootstrap resampling method with 5,000 replicates will be used to calculate 95% confidence intervals (CIs) for differences in ERRs.Using the DoseFinding package of the statistical software environment R, Emax models will be implemented to predict the dose-response curves based on CRs and ERRs.

Adverse events will be compiled into frequency tables and compared between treatment groups using descriptive summary statistics.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 210
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 5 Years

Eligibility

Inclusion Criteria:

• individuals aged 2-5 years (24-71 months; confirmed by birth certificate or similar document)

• having given written informed consent signed by parents/caregivers

• being able and willing to provide two stool samples at baseline and at follow-up assessment (14-21 days)

• having at least two out of four Kato-Katz slides positive for T. trichiura at baseline

• being able and willing to be examined by a study physician before and after treatment

Exclusion Criteria:

• presence or signs of major systemic illness, e.g. fever (temporal body temperature of >38.0°C), severe anaemia (haemoglobin level of <70 g/l)

• history of severe acute disease or unmanaged, severe chronic disease (i.e., condition is not as therapeutically controlled as necessary)

• use of anthelminthic drugs during study period

• known allergy to study medication (i.e., ivermectin or albendazole)

• being prescribed or taking concomitantly medication with known contraindications or drug interactions with the study medication

• concurrent participation in other clinical trials

Related Conditions & MeSH terms

• Ascariasis
• Hookworm Infections
• Infections
• Trichuriasis

Intervention

Drug:
• Ivermectin 1.5 mg ODT
Oro-dispersible tablets of 1.5 mg ivermectin
• Ivermectin 3 mg Oral Tablet
Tablets of 3 mg ivermectin
• Albendazole 400 mg Oral Tablet
Tablets of 400 mg albendazole
• Placebo IVM ODT
Placebo for ivermectin ODT

Locations

Country	Name	City	State
Tanzania	Public Health Laboratory Ivo de Carneri	Chake Chake

Sponsors (2)

Lead Sponsor	Collaborator
Jennifer Keiser	Public Health Laboratory Ivo de Carneri

Country where clinical trial is conducted

Tanzania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Blood concentration of ivermectin	For characterization of population pharmacokinetics (PK), ivermectin concentration will be quantified using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Drug concentrations will be calculated by interpolation from a calibration curve with a lower limit of quantification of 1-5 ng/ml.	0 to 24 hours post-treatment
Other	Acceptability of ODT assessed by visual analogue scale (0-100 mm)	To determine the acceptability of ivermectin ODTs compared to standard tablets, the palatability of each formulation will be rated by children aged 4-5 years using a visual analogue scale with continuous scores from 0 mm (worst taste) to 100 mm (best taste).	15 min post-treatment
Primary	Cure rate (CR) against T. trichiura	The CR will be calculated as the proportion of participants converting from being egg-positive pre-treatment to egg-negative post-treatment.	14-21 days post-treatment
Secondary	Egg reduction rate (ERR) against T. trichiura	Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. Geometric and arithmetic mean egg counts will be calculated for the two treatment arms before and after treatment to assess the corresponding ERRs.	14-21 days post-treatment
Secondary	Cure rate (CR) against A. lumbricoides	The CR will be calculated as the proportion of participants converting from being egg-positive pre-treatment to egg-negative post-treatment.	14-21 days post-treatment
Secondary	Egg reduction rate (ERR) against A. lumbricoides	Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. Geometric and arithmetic mean egg counts will be calculated for the two treatment arms before and after treatment to assess the corresponding ERRs.	14-21 days post-treatment
Secondary	Cure rate (CR) against Hookworm	The CR will be calculated as the proportion of participants converting from being egg-positive pre-treatment to egg-negative post-treatment.	14-21 days post-treatment
Secondary	Egg reduction rate (ERR) against Hookworm	Eggs per gram of stool (EPG) will be assessed by adding up the egg counts from the quadruplicate Kato-Katz thick smears and multiplying this number by a factor of six. Geometric and arithmetic mean egg counts will be calculated for the two treatment arms before and after treatment to assess the corresponding ERRs.	14-21 days post-treatment
Secondary	Number of participants reporting adverse events (AEs)	Participants will be monitored at the site for 3 hours following treatment for any acute AEs and reassessment will be done at 24h post-treatment. In addition, participants will be interviewed 3 and 24 hours after treatment and retrospectively at days 14-21 about the occurrence of AEs.	3 hours, 24 hours and 14-21 days post-treatment