Clinical trial NCT06736691: Efficacy and Safety of Emodepside in Participants With Soil-transmitted Helminth Infections
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Trichuris Trichiura; Infection
Hookworm Infection
Ascaris Lumbricoides Infection
Keywords: Trichuris trichiura
Ascaris lumbricoides
STH
Efficacy
Safety
Hookworm
Emodepside
Soil-transmitted helminths
Roundworm
Whipworm
Mebendazole
Lead sponsor: Swiss Tropical & Public Health Institute
Sponsor class: OTHER
Collaborators: name: Public Health Laboratory Ivo de Carneri
name: Bayer
name: Silicon Valley Community Foundation
First posted: 2024-12-17
Enrollment: 315
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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 \<50,000/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. Concomitant use as well as use within 14 days before the start of the first study intervention of strong CYP3A4 inhibitors or inducers, strong P-gp inducers and sensitive CYP3A4 substrates (detailed list of prohibited medication is provided in Section 6.5.1).
5. Concomitant use of metronidazole from 2 days before the start of the first study intervention until 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

Primary outcomes:
measure: Cured of T. trichiura infection
timeFrame: Test of Cure Visit at 14 to 21 days after end of treatment
Secondary outcomes:
measure: Cured of A. lumbricoides infection
timeFrame: Test of Cure Visit at 14 to 21 days after end of treatment
measure: Occurrence of TEAEs
timeFrame: Adverse events that occur after the first dose of study intervention up to 21 days after the last dose of study intervention
Other outcomes:
measure: Cured of hookworm infection
timeFrame: Test of Cure Visit at 14 to 21 days after end of treatment
measure: Egg reduction of each species of STH (T. trichiura, A. lumbricoides and hookworm infection)
timeFrame: Test of Cure Visit at 14 to 21 days after end of treatment
measure: Listing of individual plasma concentrations of emodepside
timeFrame: Plasma concentrations at 3, 6, 21-48 hours and 14-21 days after the end of treatment
Locations:
city: Chake Chake
country: Tanzania
facility: Public Health Laboratory - Ivo de Carneri (PHL-IdC)
Study officials:
affiliation: Swiss Tropical & Public Health Institute
name: Jennifer Keiser, Professor
role: STUDY_DIRECTOR
affiliation: Public Health Laboratory Ivo de Carneri
name: Said Mohammed Ali, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.