Efficacy and Safety of Emodepside in Adults Infected With Trichuris Trichiura and Hookworm (EMODEP_PEMBA)

Efficacy and Safety of Emodepside in Adults Infected With Trichuris Trichiura and Hookworm: Randomized Two Stages Phase II Seamless Adaptive Controlled Single-blind Trials

The rationale of the study is to provide evidence on the efficacy and safety of Emodepside in adults infected with Trichuris trichiura and hookworm.

Study Overview

• Status: Completed
• Conditions: Hookworm Infections; Trichuris Trichiura; Infection
• Intervention / Treatment: Drug: Emodepside

• Study Type: Interventional
• Enrollment (Actual): 442
• Phase: Phase 2

Contacts and Locations

Study Locations

• Tanzania
  • Chake Chake, Tanzania, 122
    • Public Health Laboratory - Ivo de Carneri

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female adults aged between 18 and 45 years
• Written and signed informed consent
• Examined by a study physician before treatment
• Provided two stool samples at baseline
• Trichuris trichiura and hookworm EPG ≥ 48 and at least two Kato-Katz thick smears slides with more than one Trichuris trichiura and hookworm eggs

Exclusion Criteria:

• Pregnant or lactating and/or planning to become pregnant within three months after drug treatment
• Type 1 and/or 2 diabetes
• Psychiatric disorders
• History of ophthalmological conditions
• Presence or history of major systemic or chronic illnesses, as assessed by a medical doctor, during initial clinical assessment
• Suffers from severe anaemia (Hb < 80 g/l)
• Received anthelminthic treatment within past four weeks
• Attending other clinical trials during the study
• Received strong CYP3A4 inducers or inhibitors as well as concomitant treatments that are relevant substrate for CYP3A4 such as clarithromycin, erythromycin and rifampicin
• Received strong P-gp inhibitors as well as concomitant treatments that are relevant substrates for P-gp such as clotrimazole and ritonavir

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
Placebo Comparator: Placebo	Drug: Emodepside; Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or albendazole (400 mg) or placebo.
Experimental: Emodepside 5 mg	Drug: Emodepside; Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or albendazole (400 mg) or placebo.
Experimental: Emodepside 10 mg	Drug: Emodepside; Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or albendazole (400 mg) or placebo.
Experimental: Emodepside 15 mg	Drug: Emodepside; Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or albendazole (400 mg) or placebo.
Experimental: Emodepside 20 mg	Drug: Emodepside; Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or albendazole (400 mg) or placebo.
Experimental: Emodepside 25 mg	Drug: Emodepside; Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or albendazole (400 mg) or placebo.
Experimental: Emodepside 30 mg	Drug: Emodepside; Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or albendazole (400 mg) or placebo.
Active Comparator: Albendazole	Drug: Emodepside; Treatment with ascending doses of emodepside (from 5 mg to 30 mg) or albendazole (400 mg) or placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cure rate (CR) of emodepside against Trichuris trichiura	CR will be calculated as the percentage of Trichuris trichiura egg-positive participants at baseline who become egg-negative after treatment.	In the week between 14 and 21 days post-treatment
Cure rate (CR) of emodepside against hookworm	CR will be calculated as the percentage of hookworm egg-positive participants at baseline who become egg-negative after treatment.	In the week between 14 and 21 days post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Egg Reduction Rate (ERR) of the emodepside against Trichuris trichiura and 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. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).	In the week between 14 and 21 days post-treatment
CR against Ascaris lumbricoides	CR will be calculated as the percentage of Ascaris lumbricoides egg-positive participants at baseline who become egg-negative after treatment.	In the week between 14 and 21 days post-treatment
ERR against Ascaris 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. The egg reduction rate (ERR) is calculated as follows: ERR = (1-(geometric mean EPG at follow-up/geometric mean EPG at baseline))*100). Note: in contrast to the publication the "outcome measure" entry mask requires the complementary percentage: (geometric mean at follow-up/geometric mean at baseline)*100).	In the week between 14 and 21 days post-treatment

Collaborators and Investigators

• Sponsor: Jennifer Keiser
• Collaborators: Public Health Laboratory Ivo de Carneri

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2021
• Primary Completion (Actual): December 10, 2021
• Study Completion (Actual): December 10, 2021

Study Registration Dates

• First Submitted: July 5, 2021
• First Submitted That Met QC Criteria: August 18, 2021
• First Posted (Actual): August 23, 2021

Study Record Updates

• Last Update Posted (Actual): May 27, 2022
• Last Update Submitted That Met QC Criteria: May 26, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Hookworm; Trichuris trichiura; Soil-transmitted helminths; Dose selection; Emodepside
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Parasitic Diseases; Secernentea Infections; Nematode Infections; Helminthiasis; Strongylida Infections; Enoplida Infections; Adenophorea Infections; Infections; Communicable Diseases; Hookworm Infections; Ancylostomiasis; Trichuriasis; Anti-Infective Agents; Antiparasitic Agents; Emodepside
• Other Study ID Numbers: EMODEP_PEMBA

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