Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202010898529928 Date of Approval: 22/10/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Emodepside phase II trial for treatment of onchocerciasis
Official scientific title A Phase-II, Randomised, Double-blind, Parallel-group Trial to Investigate Emodepside (BAY 44-4400) in Subjects with Onchocerca volvulus Infection, comprising: Part 1 to Investigate Safety, Tolerability, Pharmacodynamics, Pharmacokinetics and Dose-Response Relationship for Efficacy (Proof-of-Concept); Part 2 to Investigate Efficacy of Selected Doses, Safety, Tolerability and Pharmacokinetics
Brief summary describing the background and objectives of the trial There is an urgent need for a macrofilaricidal drug targeting the adult stage of Onchocerca volvulus, which could be used in individual case management and, after appropriate testing, as an alternative drug to ivermectin in Mass Drug Administration (MDA) programs. Emodepside is a promising drug candidate to kill the adult and sexually mature Onchocerca volvulus. Emodepside was shown to be macrofilaricidal and microfilaricidal against a variety of filarial nematodes in non-clinical studies, and is a registered drug for animal health, commercialized by Bayer AG under the name of Profender® (in combination with praziquantel) or Procox® (in combination with toltrazuril). Three Phase I trials of emodepside with single or multiple doses of emodepside have been conducted in healthy Caucasian men. The results are encouraging and support continuation of the clinical development programme of emodepside as treatment for onchocerciasis. One of these trials also enabled the selection of a field-adapted tablet formulation, suitable for use in countries endemic for onchocerciasis. The present trial is designed in a stepwise approach starting with a proof of concept part, further subdivided in steps to investigate the safety, tolerability and PK of emodepside in the target population - Part 0 (open label pilot group), followed by investigations of the safety of emodepside in low and high-microfilaria carriers - Part 1a, and the dose-response relationship for efficacy of emodepside compared to placebo in microfilaria-positive patients - Part 1b (both parts blinded). Up to two efficacious dose regimens will be selected to carry forward into the confirmatory, active-controlled, blinded Part 2 of the trial, which will investigate the superiority of emodepside over ivermectin assessed using a clinically relevant endpoint, i.e. long-term absence of microfilariae at month 24.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Onchocerciasis
Purpose of the trial Treatment: Drugs
Anticipated trial start date 19/03/2021
Actual trial start date 30/08/2021
Anticipated date of last follow up 18/09/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 578
Actual target sample size (number of participants)
Recruitment status Active, not recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
DNDi EMO 04 Sponsor
UHAS REC A.1 1 20.21 University of Health and Allied Sciences Research Ethics Committee
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Part 0 emodepside 15mg OD 1 day 15 milligrams once a day 1 day emodepside 5mg tablets x 3, taken orally, once a day for 1 day 8
Experimental Group Part 1 emodepside 30mg OD 1 day 30 milligrams once a day 1 day emodepside 5mg tablets x 6, taken orally, once a day for 1 day 30
Experimental Group Part 1 emodepside 15mg OD 7 days 15 milligrams once a day 7 days emodepside 5mg tablets x 3, taken orally once a day for 7 days 30
Experimental Group Part 1 emodepside 15mg OD 14 days 15 milligrams once a day 14 days emodepside 5mg tablets x 3, taken orally once a day for 14 days 30
Experimental Group Part 1 emodepside 15mg BID 10 days 15 milligrams twice a day 10 days emodepside 5mg tablets x 3, taken orally twice a day for 10 days 30
Control Group Part 1 placebo regimen to match experimental intervention duration to match experimental intervention matching placebo of emodepside tablets at a dose regimen to match each experimental intervention 30 Placebo
Experimental Group Part 2 emodepside regimen A Dose regimen A selected from Part 1 of the trial Dose regimen A selected from Part 1 of the trial emodepside 5mg tablets - dose regimen selected from Part 1 of the trial; plus matching placebo of ivermectin (double-dummy design) 140
Experimental Group Part 2 emodepside regimen B Dose regimen B selected from Part 1 of the trial Dose regimen B selected from Part 1 of the trial emodepside 5mg tablets - dose regimen selected from Part 1 of the trial; plus matching placebo of ivermectin (double-dummy design) 140
Control Group Part 2 ivermectin 150 micrograms per kilogram (by weight), single dose single dose 2- 4 ivermectin 3mg tablets (overencapsulated for blinding) according to body weight, participants weighing >84kg may receive additional tablets; plus matching placebo of emodepside for the double-dummy design 140 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Main Inclusion Criteria 1. Written, signed (or thumb-printed) and dated informed consent 2. Men and women 18 to 65 years of age with Onchocerca volvulus infection a. Presence of at least 1 excisable subcutaneous nodule/onchocercoma detected on palpation b. O. volvulus infection diagnosed by skin snip method, documented skin assessment on 4 skin snips. c. Body weight at Screening > 40 kg 3. For women of child-bearing potential (WOCBP), acceptance of the requirement to use a highly effective form of birth control Main Exclusion Criteria 1. Administration of medication or herbal therapies as follows: i. The following antifilarial therapies or medication that may have an antifilarial effect: • ivermectin, ≤ 6 months prior to IMP administration, and / or • doxycycline, ≤ 1 year prior to IMP administration, more than 2 weeks course, and / or • moxidectin, ≤ 2 years prior to IMP administration. ii. Other preventive chemotherapy, e.g. as part of an MDA programme within 14 days prior to IMP administration. 2. Presence of any clinically significant medical condition at Screening: including, but not limited to diabetes type 1 or 2; past or current history of neurological or neuropsychiatric disease or epilepsy; sickle cell disease; known human immunodeficiency virus (HIV) infection, disclosed by review of medical history or concomitant medication. 3. Presence of abnormal physical findings or laboratory values at Screening that could interfere with the objectives of the trial or the safety of the subject, in the opinion of the Investigator. 4. Known hypersensitivity to any ingredient of the IMP, including the active ingredient emodepside, or to ivermectin, or to any medication used during the study. 5. Current hyperreactive onchodermatitis or severe manifestations due to onchocerciasis. 6. Coincidental infection with other endemic filarial parasites based on laboratory tests at Screening (Wuchereria bancrofti, Mansonella spp.). 7. Coincidental infection with Loa loa based on medical history or positive test at Screening. 8. In groups intended to include subjects without ocular involvement: ocular microfilariae or onchocercal eye lesions, assessed at Screening. 9. Ophthalmological history or conditions that could make the ocular examination difficult or represent a risk for the safety of the subject. 10. For WOCBP: Pregnancy or breastfeeding Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 65 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 09/06/2021 University of Health and Allied Sciences Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
PMB 31 Ho, Volta Region 0000 Ghana
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 07/06/2021 Ghana Health Service Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
Research and Development Division, Ghana Health Service, P. O. Box MB190 Accra 0000 Ghana
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 18/03/2022 Ministere de la Sante Publique Comite National dethique de la Sante CNES
Ethics Committee Address
Street address City Postal code Country
Immeuble PNMLS, 1 er Niveau, Local 5, Commune de Kasa-Vubu Kinshasa 1234 Congo
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Part 1. Absence of live female adult worms with normal embryogenesis, assessed by histological examination of nodules collected on nodulectomy at Month 12. Month 12
Primary Outcome Part 1. Co-primary outcome. Absence of skin microfilariae across four skin snips sampled at Month 12. Month 12
Primary Outcome Part 2. Percentage of subjects without skin microfilariae at Month 24, assessed across all skin snips in a subject. Month 24
Secondary Outcome Part 1. The percentage of subjects with live female adult worms (assessed by histological examination of nodules collected after nodulectomy at Month 12) Month 12
Secondary Outcome Part 1. The percentage of subjects with dead female adult worms (assessed by histological examination of nodules collected after nodulectomy at Month 12) Month 12
Secondary Outcome Part 1. The percentage of subjects without skin microfilariae at all time-points after treatment. All time points after treatment
Secondary Outcome Part 1. The reduction in skin microfilarial density, defined as the mean number of mf/mg per subject, at all time-points after treatment related to baseline: change and percentage reduction at all time-points after treatment; All time points after treatment
Secondary Outcome Part 1. The presence of microfilariae in nodular tissue assessed by histological examination of nodules collected after nodulectomy at Month 12. Month 12
Secondary Outcome Part 2. The percentage of subjects without live female adult worms with normal embryogenesis (assessed by histological examination of nodules collected after nodulectomy at Month 24) Month 24
Secondary Outcome Part 2. The percentage of subjects with live female adult worms (assessed by histological examination of nodules collected after nodulectomy at Month 24) Month 24
Secondary Outcome Part 2. The percentage of subjects with dead female adult worms (assessed by histological examination of nodules collected after nodulectomy at Month 24) Month 24
Secondary Outcome Part 2. The percentage of subjects with live female adult worms with normal embryogenesis (assessed by histological examination of nodules collected after nodulectomy at Month 24) Month 24
Secondary Outcome Part 2. The percentage of subjects without skin microfilariae at all time-points after treatment All time points after treatment
Secondary Outcome Part 2. The reduction in skin microfilarial density, defined as the mean number of mf/mg per subject, at all time-points after treatment related to baseline: change and percentage reduction at all time-points after treatment. All time points after treatment
Secondary Outcome Part 2. The presence of microfilariae in nodular tissue, assessed by histological examination of nodules collected on nodulectomy at Month 24. Month 24
Secondary Outcome Safety and Tolerability Outcome - Parts 1 and 2 - Safety and tolerability of emodepside. As measured by adverse event assessment, physical examination, skin examination, neurological examination, vital signs, 12-lead electrocardiogram, clinical laboratory tests, and ophthalmological examination All time points after treatment
Secondary Outcome PK/PD outcome - Part 1 and Part 2 - AUCtau, Cmax, Cmin, clearance and t½ for emodepside. Time above given concentrations may also be estimated. Sampling points between day 0 to 28 according to the dose regimen
Secondary Outcome PK/PD outcome - Part 1 and Part 2 - The relationship between the presence or absence of skin microfilariae at Month 12 and Month 24 with respect to emodepside pharmacokinetic parameters Month 12 and Month 24
Secondary Outcome PK/PD outcome - Part 1 and Part 2 - The relationship between reduction in mean skin microfilarial density over time, with respect to emodepside pharmacokinetic parameters All time points after treatment
Secondary Outcome PK/PD outcome - Part 1 and Part 2 - The relationship between percentage of live female adult worms and percentage of live female adult worms with normal embryogenesis with respect to emodepside pharmacokinetic parameters All time points after treatment
Secondary Outcome PK/PD outcome - Part 1 and Part 2 - The relationship between safety and tolerability parameters with respect to emodepside pharmacokinetic parameters. All time points after treatment
Secondary Outcome Exploratory outcome - Part 1 and Part 2 - Microfilaria levels in the cornea, anterior and posterior segment, measured in both eyes at all time-points when ophthalmological assessments are performed All time points after treatment
Secondary Outcome Exploratory outcome - Part 1 and Part 2 - The presence, severity and clinical evolution of onchocerciasis ocular disease, onchocerciasis skin disease, and itching at all time-points when ophthalmological or skin examinations are performed All time points after treatment
Primary Outcome Part 0. Safety and tolerability of emodepside in O. volvulus infected subjects, as measured by adverse event assessment, physical examination, skin examination, neurological examination, vital signs, 12-lead electrocardiogram, clinical laboratory tests, and ophthalmological examination up to end of study
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
School of Public Health University of Health and Allied Sciences Hohoe Ghana
Centre de sante de reference Kimpese Manyaki Congo
Hopital general de reference Masi-Manimba Masimanimba Congo
FUNDING SOURCES
Name of source Street address City Postal code Country
Drugs for Neglected Diseases Initiative 15 Chemin Louis-Dunant Geneva 1202 Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Drugs for Neglected Diseases Initiative 15 Chemin Louis-Dunant Geneva 1202 Switzerland Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
Bayer AG Muellerstrasse 178 Berlin 13353 Germany
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Nicholas Opoku noopoku@uhas.edu.gh +233244776668 University of Health and Allied Services School of Public Health
City Postal code Country Position/Affiliation
Hohoe Ghana Principal Investigator
Role Name Email Phone Street address
Public Enquiries Virginie Pillet vpillet@dndi.org +41796930161 15 Chemin Camille Vidart
City Postal code Country Position/Affiliation
Geneva 1202 Switzerland DNDi Senior Clinical Project Manager
Role Name Email Phone Street address
Scientific Enquiries Sabine Specht sspecht@dndi.org +41229069230 15 Chemin Camille Vidart
City Postal code Country Position/Affiliation
Geneva 1202 Switzerland DNDi Head of Filarial Clinical Programme
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Summary results will be shared once Clinical Study Report will be available Study Protocol Within 12 months of Clinical Study report finalization Open access
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information