Efficacy and Safety of Emodepside in Participants With Soil-transmitted Helminth Infections (TREMO-Siargao)

A Phase III Single-center, Randomized, Double-Blinded, Parallel-group, Active Controlled Study to Evaluate the Efficacy and Safety of a Single Dose of Emodepside Compared to Multiple Doses of Mebendazole in Adolescent and Adult Participants With Soil-transmitted Helminthiasis

This study aims to assess the efficacy and safety of emodepside compared to mebendazole in adults and adolescents infected with T. trichiura, either as single infection or co-infections with hookworm and/or A. lumbricoides.

Study Overview

• Status: Not yet recruiting
• Conditions: Hookworm Infection; Ascaris Lumbricoides Infection; Trichuris Trichiura; Infection
• Intervention / Treatment: Drug: emodepside (BAY 44-4400); Drug: similar placebo to mebendazole; Drug: matching placebo of emodepside; Drug: Mebendazole 100 MG

• Study Type: Interventional
• Enrollment (Estimated): 315
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jennifer Keiser, Professor; Phone Number: +41 61 284 82 18; Email: jennifer.keiser@swisstph.ch

Study Locations

• Philippines
  • Manila, Philippines
    • University of the Philippines Manila
    • Contact: Ma. Cecilia D. Alinea, Clinical Associate Professor; Phone Number: 2100 +63 285448400; Email: mdalinea@up.edu.ph
    • Contact: Vicente Belizario Jr., Adjunct Research Professor; Phone Number: (+63) 917 5261359; Email: vybelizario@up.edu.ph
    • Principal Investigator: Ma. Cecilia D. Alinea, Clinical Associate Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or non-pregnant (confirmed by a negative serum pregnancy test) and non-breastfeeding female participants aged 12 years and older.
2. T. trichiura as a single infection or co-infection with hookworm and/or A. lumbricoides, confirmed by presence of T. trichiura eggs assessed by Kato-Katz thick smears from two stool samples (infection intensity defined as number of eggs per gram of stool (EPG): (1) light (1-999 EPG), (2) moderate to heavy (≥1000 EPG).
3. A minimum infection intensity of 24 eggs per gram of stool at baseline and at least two positive slides out of the four slides assessed at baseline.
4. Written informed consent signed by the participant and/or legally authorized representative(s) according to the participant's age as established per local regulations. In addition, participant's assent is required as applicable by local laws and regulations for adolescents of 12-17 years of age.
5. Women of childbearing potential must agree to use an effective, culturally appropriate contraceptive measure from at least 28 days prior to first dosage for hormonal contraceptives only and for non-hormonal contraceptive measures from screening Visit 2 until End of Study Visit.

Exclusion Criteria:

1. Presence of any systemic illnesses, renal and/or hepatic impairment, any other acute or chronic health conditions or congenital disorders which, in the opinion of the Investigator, would make the participant unsuitable for participation in a clinical study or may interfere with the efficacy, safety, and/or pharmacokinetic (PK) evaluation of the study drug.

2. Any of the following:

   1. Platelet <75,000/mm3
   2. Alanine Aminotransferase (ALT) or Serum Glutamic Pyruvic Transaminase (SGPT) >3x upper limit of normal (ULN)
   3. Total bilirubin >2xULN
   4. Estimated Glomerular Filtration Rate (eGFR) <90 ml/min/1.73 m2 (adolescents) or estimated creatinine clearance (CrCl) <90 ml/ min (adults)
3. Treatment with the following anthelminthic drugs: albendazole, mebendazole, ivermectin, within 28 days before the first dose of study intervention or planned before End of Study Visit.
4. Use of sensitive CYP3A4 substrates within 14 days before the start of the first study intervention and until at least 14 days after the last administration of study intervention.
5. Treatment with metronidazole within 2 days before the first dose of study intervention or planned before 24 hours after last administration of study intervention.
6. Previous assignment to a study intervention for another study planned to be administered during the period the participant is enrolled in this study (from date of informed consent to last follow-up).
7. Known allergy/hypersensitivity to mebendazole and/or emodepside

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Emodepside	Drug: emodepside (BAY 44-4400); Treatment with single dose of oral 15 mg emodepside; Drug: similar placebo to mebendazole; Treatment with mebendazole similar placebo orally administered b.i.d. for 3 days
Active Comparator: Mebendazole	Drug: matching placebo of emodepside; Treatment with single dose of oral emodepside matching placebo; Drug: Mebendazole 100 MG; Treatment with 100 mg mebendazole orally administered b.i.d. for 3 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cured of T. trichiura infection	Determined by negative Kato-Katz thick smears in two stool samples taken at the Test of Cure Visit	Test of Cure Visit at 14 to 21 days after end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of TEAEs	Defined as any AE that occurred or worsened after the first dose of study intervention up to 21 days after the last dose of study intervention	Adverse events that occur after the first dose of study intervention up to 21 days after the last dose of study intervention
Cured of A. lumbricoides infection	Determined by negative Kato-Katz thick smears in two stool samples taken at the Test of Cure Visit. This endpoint is only applicable for the subgroup of participants co-infected with A. lumbricoides at baseline.	Time Frame: Test of Cure Visit at 14 to 21 days after end of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Egg reduction of each species of STH (T. trichiura, A. lumbricoides and hookworm infection)	Defined as logarithm of the number of eggs/g (+1) from stool samples taken at the Test of Cure Visit minus the logarithm of the number of eggs/g (+1) in stool samples taken at baseline. Egg reduction of A. lumbricoides and hookworm will only be calculated in participants co-infected with A. lumbricoides and hookworm at baseline, respectively.	Test of Cure Visit at 14 to 21 days after end of treatment
Listing of individual plasma concentrations of emodepside		Plasma concentrations at 3, 6, 21-48 hours and 14-21 days after the end of treatment
Cured of hookworm infection	Determined by negative Kato-Katz thick smears in two stool samples taken at the Test of Cure Visit. This endpoint is only applicable for the subgroup of participants co-infected with hookworm at baseline.	Test of Cure Visit at 14 to 21 days after end of treatment

Collaborators and Investigators

• Sponsor: Swiss Tropical & Public Health Institute
• Collaborators: Bayer; University of the Philippines; Silicon Valley Community Foundation
• Investigators: Study Director: Jennifer Keiser, Professor, Swiss Tropical & Public Health Institute

Publications and helpful links

General Publications

• Taylor L, Ahmada AA, Ali MS, Ali SM, Hattendorf J, Mohammed IS, Keiser J. Efficacy and safety of emodepside compared with albendazole in adolescents and adults with hookworm infection in Pemba Island, Tanzania: a double-blind, superiority, phase 2b, randomised controlled trial. Lancet. 2024 Aug 17;404(10453):683-691. doi: 10.1016/S0140-6736(24)01403-X.
• Mrimi EC, Welsche S, Ali SM, Hattendorf J, Keiser J. Emodepside for Trichuris trichiura and Hookworm Infection. N Engl J Med. 2023 May 18;388(20):1863-1875. doi: 10.1056/NEJMoa2212825.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: January 23, 2025
• First Submitted That Met QC Criteria: January 23, 2025
• First Posted (Actual): January 29, 2025

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Hookworm; Mebendazole; STH; Trichuris trichiura; Whipworm; Soil-transmitted helminths; Emodepside; Ascaris lumbricoides; Roundworm
• Additional Relevant MeSH Terms: Infections; Parasitic Diseases; Secernentea Infections; Nematode Infections; Helminthiasis; Enoplida Infections; Adenophorea Infections; Strongylida Infections; Oxyuriasis; Oxyurida Infections; Trichuriasis; Hookworm Infections; Ancylostomiasis; Enterobiasis; Organic Chemicals; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Acids, Acyclic; Carboxylic Acids; Carbamates; Mebendazole; emodepside; Bay 44-4400
• Other Study ID Numbers: P2810-23B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: There is a data sharing agreement between Swiss TPH and PHL-IdC in place (study site). Data may be shared with other researchers upon request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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