Emodepside phase II trial for treatment of onchocerciasis

INTERVENTION: Part 0 emodepside 15mg OD 1 day Part 1 emodepside 15mg BID 10 days Part 1 emodepside 15mg OD 14 days Part 1 emodepside 15mg OD 7 days Part 1 emodepside 30mg OD 1 day Part 1 placebo Part 2 emodepside regimen A Part 2 emodepside regimen B Part 2 ivermectin CONDITION: ; Onchocerciasis Onchocerciasis 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 Part 1. Absence of live female adult worms with normal embryogenesis, assessed by histological examination of nodules collected on nodulectomy at Month 12. Part 1. Co‐primary outcome. Absence of skin microfilariae across four skin snips sampled at Month 12. Part 2. Percentage of subjects without skin microfilariae at Month 24, assessed across all skin snips in a subject. INCLUSION CRITERIA: 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 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 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 Part 1. The percentage of subjects with dead female adult worms (assessed by histological examination of nodules collected after nodulectomy at Month 12) Part 1. The percentage of subjects with live female adult worms (assessed by histological examination of nodules collected after nodulectomy at Month 12) Part 1. The percentage of subjects without skin microfilariae at all time‐points after treatment. Part 1. The presence of microfilariae in nodular tissue assessed by histological examination of nodules collected after nodulectomy at Month 12. 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; Part 2. The percentage of subjects with dead female adult worms (assessed by histological examination of nodules collected after nodulectomy at Month 24) Part 2. The percentage of subjects with live female adult worms (assessed by histological examination of nodules collected after nodulectomy at Month 24) 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) 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) Part 2. The percentage of subjects without skin microfilariae at all time‐points after treatment Part 2. The presence of microfilariae in nodular tissue, assessed by histological examination of nodules collected on nodulectomy at Month 24. 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. PK/PD outcome ‐ Part 1 and Part 2 ‐ AUCtau, Cmax, Cmin, clearance and t½ for emodepside. Time above given concentrations may also be estimated. 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 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 PK/PD outcome ‐ Part 1 and Part 2 ‐ The relationship between safety and tolerability parameters with respect to emodepside pharmacokinetic parameters. 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 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