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

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: Enrolling by invitation
• 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

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

Contacts and Locations

Study Locations

• Tanzania
  • Chake Chake, Tanzania
    • Public Health Laboratory - Ivo de Carneri (PHL-IdC)

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 (detailed list of prohibited medication is provided in Section 6.5.1).
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; 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
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.	Test of Cure Visit at 14 to 21 days after end of treatment
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Swiss Tropical & Public Health Institute
• Collaborators: Bayer; Silicon Valley Community Foundation; Public Health Laboratory Ivo de Carneri
• Investigators: Study Director: Jennifer Keiser, Professor, Swiss Tropical & Public Health Institute; Principal Investigator: Said Mohammed Ali, MSc, Public Health Laboratory Ivo de Carneri

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 (Actual): November 25, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: December 12, 2024
• First Submitted That Met QC Criteria: December 12, 2024
• First Posted (Actual): December 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 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: P2810-23A

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