Emodepside Phase II Trial for Treatment of Onchocerciasis
- Conditions
- Onchocerciasis
- Interventions
- Drug: matching placebo of emodepsideDrug: matching placebo of ivermectin
- Registration Number
- NCT05180461
- Lead Sponsor
- Drugs for Neglected Diseases
- Brief Summary
The trial evaluates safety, tolerability, pharmacodynamics, pharmacokinetics, dose-response, and efficacy of emodepside tablets, administrated as a range of dose regimens, in adults infected with Onchocerca Volvulus.
- Detailed Description
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, which is further subdivided in steps to investigate the safety, tolerability and pharmacokinetics of emodepside in the target population - Part 0 (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. This approach allows to maximize the information regarding the safety of emodepside in the target population and to establish a dose range, in which emodepside is efficacious. Based on the information obtained from Parts 0 and 1, up to two efficacious dose regimens will be selected to carry forward into the confirmatory, active-controlled 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 578
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1 placebo matching placebo of emodepside matching placebo of emodepside tablets Part 2 ivermectin matching placebo of emodepside ivermectin, single oral dose of 150 micrograms per kilogram by weight Part 2 emodepside dose regimen A matching placebo of ivermectin emodepside tablets, dose regimen A selected from regimens tested in Part 1 Part 2 emodepside dose regimen B matching placebo of ivermectin emodepside tablets, dose regimen B selected from regimens tested in Part 1 Part 2 ivermectin ivermectin ivermectin, single oral dose of 150 micrograms per kilogram by weight Part 0 Pilot group emodepside 15mg Once a day (OD) 1 day emodepside emodepside tablets 15 milligrams once a day for 1 day Part 1 emodepside 30mg OD 1 day emodepside emodepside tablets 30 milligrams once a day for 1 day Part 1 emodepside 15mg OD 7 days emodepside emodepside tablets 15 milligrams once a day for 7 days Part 1 emodepside 15mg OD 14 days emodepside emodepside tablets 15 milligrams once a day for 14 days Part 1 emodepside 15mg twice a day (BID) 10 days emodepside emodepside tablets 15 milligrams twice a day for 10 days Part 2 emodepside dose regimen A emodepside emodepside tablets, dose regimen A selected from regimens tested in Part 1 Part 2 emodepside dose regimen B emodepside emodepside tablets, dose regimen B selected from regimens tested in Part 1
- Primary Outcome Measures
Name Time Method Part 2 - absence (or presence) of skin microfilariae 24 months Absence (or presence) of skin microfilariae, assessed across all skin snips in a participant
Part 1 - absence (or presence) of skin microfilariae (co-primary outcome) 12 months Absence (or presence) of skin microfilariae across four skin snips
Part 1 - absence (or presence) of live female adult worms with normal embryogenesis 12 months Absence (or presence) of live female adult worms with normal embryogenesis, assessed by histological examination of nodules collected on nodulectomy
- Secondary Outcome Measures
Name Time Method Part 1- absence (or presence) of live female adult worms 12 months The absence (or presence) of live female adult worms, assessed by histological examination of nodules collected after nodulectomy
Part 1 - Absence (or presence) of microfilariae in nodular tissue 12 months The absence (or presence) of microfilariae in nodular tissue assessed by histological examination of nodules collected after nodulectomy
Part 2 - Presence (or absence) of dead female adult worms 24 months Presence (or absence) of dead female adult worms, assessed by histological examination of nodules collected after nodulectomy
Part 1 - presence (or absence) of dead female adult worms 12 months The presence (or absence) of dead female adult worms, assessed by histological examination of nodules collected after nodulectomy
Part 1 - reduction in skin microfilarial density up to 12 months The reduction in skin microfilarial density, defined as the mean number of microfilariae per milligram per subject, at all time-points after treatment related to baseline: change and percentage reduction
Part 2 - The reduction in skin microfilarial density up to 24 months The reduction in skin microfilarial density, defined as the mean number of microfilariae per milligram per subject, at all time-points after treatment related to baseline: change and percentage reduction
Part 1 - Absence (or presence) of skin microfilariae up to 12 months Absence (or presence) of skin microfilariae
Part 2 - Absence (or presence) of live female adult worms with normal embryogenesis 24 months Absence (or presence) of live female adult worms with normal embryogenesis assessed by histological examination of nodules collected after nodulectomy.
Part 2 - Absence (or presence) of live female adult worms 24 months Absence (or presence) of live female adult worms, assessed by histological examination of nodules collected after nodulectomy
Part 2 - Absence (or presence) of skin microfilariae up to 24 months Absence (or presence) of skin microfilariae
Part 2 - Absence (or presence) of microfilariae in nodular tissue 24 months The absence (or presence) of microfilariae in nodular tissue, assessed by histological examination of nodules collected on nodulectomy
Trial Locations
- Locations (3)
University of Health and Allied Services School of Public Health
🇬🇭Hohoe, Volta Region, Ghana
Hôpital général de référence de Masimanimba
🇨🇩Masi-Manimba, Kwilu, Congo, The Democratic Republic of the
Centre de santé de référence de Kimpese
🇨🇩Kimpese, Kongo Central, Congo, The Democratic Republic of the