Efficacy and Safety of Emodepside in Adults Infected With Strongyloidiasis Stercoralis

Efficacy, Safety and Pharmacokinetics of Ascending Dosages of Emodepside and in Comparison to Ivermectin Against Strongyloidiasis Stercoralis in Adults: Randomized Stage II Seamless Adaptive Controlled Trials

Efficacy, safety and pharmacokinetics of ascending dosages of emodepside and in comparison to ivermectin against Strongyloidiasis stercoralis in adults: randomized stage II seamless adaptive controlled trials

Study Overview

• Status: Completed
• Conditions: Strongyloidiasis; Strongyloides Stercoralis Infection
• Intervention / Treatment: Drug: Emodepside

• Study Type: Interventional
• Enrollment (Actual): 202
• Phase: Phase 2

Contacts and Locations

Study Locations

• Lao People's Democratic Republic
  • Vientiane, Lao People's Democratic Republic
    • Lao Tropical and Public Health Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent signed by the participant him/herself
• Males and females of age 18 or older
• Infected with S. stercoralis (positive by at least two Baermann assays on two different days and infection intensities of at least 0.75 LPG in the two stool samples.
• Agree to comply with the study procedures, including to be examined by a study physician at the beginning of the study and to provide three stool samples during the screening period (within a maximum of 10 days) and approximately three weeks after treatment (follow-up).
• Female participants of childbearing potential to ensure adequate contraception during the study period.

Exclusion Criteria:

• No written informed consent by individual.
• Presence of acute or uncontrolled systemic illnesses (e.g. severe anemia, clinical malaria) as assessed by a medical doctor, upon initial clinical assessment.
• Recent history of acute or severe chronic disease, as assessed by a medical doctor or reported by the participant: Type 1 and/or 2 diabetes; Psychiatric disorders; Chronic heart, liver, or renal disease
• Prior treatment with anthelmintics (eg, diethylcarbamazine [DEC], suramin, ivermectin, mebendazole or albendazole) within 4 weeks before planned study drug administration.
• Actively participating in other clinical trials during the study.
• Positive pregnancy test or breastfeeding women and planning to become pregnant within three months of study drug administration.
• Received strong CYP3A4 inducers or inhibitors as well as concomitant treatments that are relevant substrate for CYP3A4 such as clarithromycin, erythromycin and rifampicin within 4 weeks before planned study drug administration.
• Received strong P-gp inhibitors as well as concomitant treatments that are relevant substrates for P-gp such as clotrimazole and ritonavir.
• Known allergy to study drugs or any of the ingredients

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Emodepside 5 mg; Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or ivermectin (200 μg/kg) or placebo.	Drug: Emodepside; 5 mg tablets of emodepside and matching placebo tablets, 3mg ivermectin
Experimental: Emodepside 10 mg; Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or ivermectin (200 μg/kg) or placebo.	Drug: Emodepside; 5 mg tablets of emodepside and matching placebo tablets, 3mg ivermectin
Experimental: Emodepside 15 mg; Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or ivermectin (200 μg/kg) or placebo.	Drug: Emodepside; 5 mg tablets of emodepside and matching placebo tablets, 3mg ivermectin
Experimental: Emodepside 20 mg; Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or ivermectin (200 μg/kg) or placebo.	Drug: Emodepside; 5 mg tablets of emodepside and matching placebo tablets, 3mg ivermectin
Experimental: Emodepside 25 mg; Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or ivermectin (200 μg/kg) or placebo.	Drug: Emodepside; 5 mg tablets of emodepside and matching placebo tablets, 3mg ivermectin
Experimental: Emodepside 30 mg; Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or ivermectin (200 μg/kg) or placebo.	Drug: Emodepside; 5 mg tablets of emodepside and matching placebo tablets, 3mg ivermectin
Placebo Comparator: Placebo; Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or ivermectin (200 μg/kg) or placebo.	Drug: Emodepside; 5 mg tablets of emodepside and matching placebo tablets, 3mg ivermectin
Active Comparator: Ivermectin 3 mg; Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or ivermectin (200 μg/kg) or placebo.	Drug: Emodepside; 5 mg tablets of emodepside and matching placebo tablets, 3mg ivermectin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cure rate (CR) of emodepside against Strongyloides stercoralis	The CR will be calculated as the proportion of Strongyloides stercoralis larvae-positive participants at baseline who become larvae-negative after treatment.	In the week between 14 and 21 days post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of the dose-dependent emodepside treatment regimes, and compared with ivermectin.	AEs will be evaluated descriptively as the difference of proportion reported AEs before and after treatment.	Actively evaluated at 3 hours, 24 hours, 72 hours, and 14 days post-treatment
Geometric Mean Larvae Reduction Rate (LRR) of emodepside against Strongyloides stercoralis.	The LRRs will be calculated based on the geometric mean	In the week between 14 and 21 days post-treatment
Exposure response of emodepside in adults	Emodepside 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 foreseen limit of quantification of approximately 1-5 ng/ml.	Actively collected at 0 hours, 0.5 hours, 2.5 hours, 5 hours, 24 hours, 72 hours, and 14 days post-treatment
Cure rate (CR) and egg reduction rate (ERR) with other soil-transmitted helminths (STH) and trematodes	The CR will be calculated as the proportion of the STH or trematode positive participants at baseline who become egg-negative after treatment. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100).	In the week between 14 and 21 days post-treatment

Collaborators and Investigators

• Sponsor: Swiss Tropical & Public Health Institute
• Collaborators: National Institute of Public Health, Vientiane, Laos

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2024
• Primary Completion (Actual): September 21, 2024
• Study Completion (Actual): September 21, 2024

Study Registration Dates

• First Submitted: April 16, 2024
• First Submitted That Met QC Criteria: April 16, 2024
• First Posted (Actual): April 18, 2024

Study Record Updates

• Last Update Posted (Estimated): November 20, 2024
• Last Update Submitted That Met QC Criteria: November 19, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Parasitic Diseases; Secernentea Infections; Nematode Infections; Helminthiasis; Rhabditida Infections; Strongyloidiasis; Anti-Infective Agents; Antiparasitic Agents; Emodepside
• Other Study ID Numbers: EMODEPSIDE_LAOS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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