Efficacy and Safety of Moxidectin Versus Ivermectin Against Strongyloides Stercoralis (StrongMoxi_KH)

Efficacy and Safety of Moxidectin in Comparison to Ivermectin Against Strongyloides Stercoralis Infection in Adults: a Randomized Controlled Non-inferiority Trial

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.

Study Overview

• Status: Completed
• Conditions: Strongyloides Stercoralis Infection
• Intervention / Treatment: Drug: Placebo; Drug: Ivermectin 3 mg; Drug: Moxidectin 2 mg

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.

• Study Type: Interventional
• Enrollment (Actual): 332
• Phase: Phase 3

Contacts and Locations

Study Locations

• Cambodia
  • Phnom Penh, Cambodia
    • National Centre for Parasitology, Entomology and Malaria Control

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Moxidectin; 8 mg Moxidectin at day 0 administered orally	Drug: Placebo; Monotherapy, oral administration, single dose, matching number of tablets to either moxidectin or ivermectin; Drug: Moxidectin 2 mg; Monotherapy, oral administration, single-dose, fixed-dose, 4 tablets of 2 mg each to yield an 8 mg final dose.
Experimental: Ivermectin; 200 ug/kg Ivermectin at day 0 administered orally	Drug: Placebo; Monotherapy, oral administration, single dose, matching number of tablets to either moxidectin or ivermectin; Drug: Ivermectin 3 mg; Monotherapy, oral administration, single-dose, weight dependent, The number of tablets will be adjusted according to the patients' weight to yield 200 ug/kg final dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cure Rate Against Strongyloides Stercoralis	The conversion from being larvae positive pre-treatment to larvae negative post-treatment, or cure rate (CR).	14-21 days after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CRs Against Concomitant Soil-transmitted Helminth Infections - Ascaris Lumbricoides	CRs will be calculated for Ascaris lumbricoides, Trichuris trichiura and hookworm infections as described in primary outcome.	14-21 days after treatment
CRs Against Concomitant Soil-transmitted Helminth Infections - Trichuris Trichiura	CRs will be calculated for Ascaris lumbricoides, Trichuris trichiura and hookworm infections as described in primary outcome.	14-21 days after treatment
CRs Against Concomitant Soil-transmitted Helminth Infections - Hookworm	CRs will be calculated for Ascaris lumbricoides, Trichuris trichiura and hookworm infections as described in primary outcome.	14-21 days after treatment
Larvae Reduction Rate (LRR) Against Strongyloidiasis Stercoralis	Larvae per gram (LPG) stool sample will be assessed by calculating the mean of the larvae counts from the three duplicate Baermann assays and divided by the mean weighted amount of these stool samples. The LRR will be calculated following: (LRR = (1-(mean at follow-up/mean at baseline))*100)	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.
Number of Participants Reporting Adverse Events	Participants will be monitored on site for at least 3 hours following treatment for any acute adverse events. In addition, participants will be interviewed 2-3 and 24 hours and at several weeks after treatment about the occurrence of adverse events. A standardized symptom questionnaire is used, that includes the recording of headache, abdominal pain, itching, nausea, vomiting, diarrhea, allergic reaction as well as any further mentioned event by the participant.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Socioeconomic Characteristics (SES)	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.	Pre-treatment
Genetic Profiling of S. Stercoralis Positive Stool Samples	From all S. stercoralis positive stool samples, the extracted larvae will be stored in 70% Ethanol after examination by Baermann. Samples will be shipped to the investigating laboratory (La Trobe University) at room temperature.	Pre-treatment

Collaborators and Investigators

• Sponsor: Jennifer Keiser
• Collaborators: National Centre for Parasitology, Entomology and Malaria Control, Cambodia
• Investigators: Principal Investigator: Jennifer Keiser, Prof. Dr, STPH

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2022
• Primary Completion (Actual): July 17, 2022
• Study Completion (Actual): July 17, 2022

Study Registration Dates

• First Submitted: April 8, 2021
• First Submitted That Met QC Criteria: April 13, 2021
• First Posted (Actual): April 19, 2021

Study Record Updates

• Last Update Posted (Estimated): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Parasitic Diseases; Secernentea Infections; Nematode Infections; Helminthiasis; Rhabditida Infections; Infections; Strongyloidiasis; Anti-Infective Agents; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Ivermectin; Moxidectin
• Other Study ID Numbers: 4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No