Clinical trial NCT04848688: Efficacy and Safety of Moxidectin Versus Ivermectin Against Strongyloides Stercoralis
Official title: Efficacy and Safety of Moxidectin in Comparison to Ivermectin Against Strongyloides Stercoralis Infection in Adults: a Randomized Controlled Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Strongyloides Stercoralis Infection
Lead sponsor: Swiss Tropical & Public Health Institute
Sponsor class: OTHER
Collaborators: name: National Centre for Parasitology, Entomology and Malaria Control, Cambodia
First posted: 2021-04-19
Enrollment: 332
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel study with 2 treatment arms
Primary purpose: TREATMENT

Brief summary: The study is an extension to the study StrongMoxi NCT04056325 and entails modifications based on the outcome of NCT04056325 part A.

The study is a phase 3, double-blinded and randomized clinical trial conducted in Cambodia. It aims at providing evidence on efficacy, safety and pharmacokinetic measures of 8 mg of moxidectin compared to 200 μg/kg ivermectin in adults infected with S. stercoralis. The efficacy of the treatment will be assessed by collecting three stool samples once per-treatment and once 21-28 days post-treatment. The stool samples will be analyzed by a quantitative duplicate Baermann assay.

Detailed description: The study is a phase 3 trial and will determine the efficacy and safety of:

8 mg of moxidectin in comparison to the standard treatment dose of ivermectin (200 μg/kg) in adults infected with S. stercoralis and to measure moxidectin disposition in adults using a microsampling device.

Our primary objective is to demonstrate non-inferiority in terms of cure rate (CR) against S. stercoralis in adults of an oral 8 mg of moxidectin compared to 200 μg/kg of ivermectin.

The secondary objectives of the trial are:

1. to evaluate the safety and tolerability of moxidectin
2. to compare the larval reduction rate (LRR) of the two different treatment groups against S. stercoralis
3. to evaluate the CRs of the different treatment drugs and regimens against soil-transmitted helminths (STH) co-infections.
4. to investigate potential extended effects on follow-up helminth prevalence at 42-49 and 63-70 days post-treatment
5. to relate socioeconomic characteristics (SES), access to sanitation, water facilities, hygiene to baseline infection intensity.
6. to determine the larval excretion pattern till day 70 in the moxidectin treatment arm, determined at every second day between day zero and 70 post-treatment in a subset of 50 adults.
7. to determine the origin of the remaining worm burden after treatment to treatment failure and reinfection based on genetic profiling.

Three stool samples will be collected at baseline analysed in duplicates by a quantitative Baermann method for S. stercoralis infection. Co-infection with other Helminths species will be identified using duplicate Kato-Katz thick smears on two stool samples. The medical history of the participants will be assessed with a standardized questionnaire, in addition to a clinical and physical examination carried out by the study physician shortly before the treatment day. Each participant will be asked to provide a finger-prick blood sample for haemoglobin measurements at baseline. Enrolled participants will be treated with either 8 mg of moxidectin or with the standard treatment ivermectin (200 μg/kg). The adults will be interviewed a) before treatment, 2-3 and 24 hours as well as 14-21, 42-49 and 63-70 days after treatment about the occurrence of adverse events. The efficacy of the treatment will be determined 14-21 days of post-treatment. All stool samples will be examined with quantitative sixtuplicate Baermann assays and quadruplet Kato-Katz thick smears. At 42-49 and 63-70 days post-treatment another three stool samples will be collected and quantified for S. stercoralis larvae using Baermann assay to assess potential long-term benefits of the study drugs and treatment regimen. Of 50 adults in the moxidectin arm only, additional stool samples will be collected every second day between treatment and 70 days post treatment to evaluate larval secretion patterns.

To all participating households, a brief questionnaire will be administered assessing information on socioeconomic characteristics (SES) and access to sanitation, water facilities, and hygiene behaviour.

An available case analysis (full analysis set according to the intention to treat principle) will be performed, including all participants with primary endpoint data.

CRs will be calculated as the percentage of larvae-positive subjects at baseline who become larvae-negative after treatment, assessed 14-21 days post-treatment by sextuplicate Baermann. Uncertainty estimates around the differences among CRs will be assessed using melded confidence intervals with mid-p correction. The non-inferiority.

Eligibility criteria: Inclusion Criteria:

* Adults (18-65 years)
* Infected with S. stercoralis (positive)
* Absence of major systemic illnesses
* Written informed consent

Exclusion Criteria:

* Any abnormal medical conditions or chronic disease
* Negative diagnostic result for S. stercoralis
* No written informed consent by the individual.
* Pregnant and lactating women.
* Recent use of an anthelmintic drug (within past 4 weeks)
* Attending other clinical trials during the study
* Known allergy to study medications (i.e. moxidectin, ivermectin)
* Currently taking medications with known interaction (i.e. for warfarin)

Primary outcomes:
measure: Cure Rate Against Strongyloides Stercoralis
timeFrame: 14-21 days after treatment
Secondary outcomes:
measure: Larvae Reduction Rate (LRR) Against Strongyloidiasis Stercoralis
timeFrame: 14-21 days after treatment. The originally planned follow-ups at 42-49 days and 63-70 days as well as the sample collection every second day between day 0 and day 70 (Moxidectin arm, n=50) was not performed.
measure: CRs Against Concomitant Soil-transmitted Helminth Infections - Ascaris Lumbricoides
timeFrame: 14-21 days after treatment
measure: CRs Against Concomitant Soil-transmitted Helminth Infections - Trichuris Trichiura
timeFrame: 14-21 days after treatment
measure: CRs Against Concomitant Soil-transmitted Helminth Infections - Hookworm
timeFrame: 14-21 days after treatment
measure: Number of Participants Reporting Adverse Events
timeFrame: 2-3 hours, 24 hours and 14-21 days after treatment. The originally planned follow-ups at 42-49 days and 63-70 days after treatment were not conducted.
Other outcomes:
measure: Socioeconomic Characteristics (SES)
timeFrame: Pre-treatment
measure: Genetic Profiling of S. Stercoralis Positive Stool Samples
timeFrame: Pre-treatment
Locations:
city: Phnom Penh
country: Cambodia
facility: National Centre for Parasitology, Entomology and Malaria Control
Study officials:
affiliation: STPH
name: Jennifer Keiser, Prof. Dr
role: PRINCIPAL_INVESTIGATOR
References: