| Eligibility |
Inclusion Criteria for Part 1:
1. Written, signed (or thumb-printed) and dated informed consent, after having the
opportunity to discuss the study with the Investigator or a delegate.
2. Men and women with Onchocerca volvulus infection, 18 to 65 years of age inclusive at
time of Screening,
1. Presence of at least 1 excisable subcutaneous nodule/onchocercoma detected on
palpation
2. O. volvulus infection diagnosed by skin snip method: documented mf-positivity on
skin assessment on at least 2 out of 4 skin snips.
- i. For Part 0: subjects with low microfilarial load, skin microfilarial
density > 0 and < 10 microfilariae/mg and without ocular involvement
- ii. For Part 1a:
- In groups with low microfilarial load, skin microfilarial density > 0
and < 10 microfilariae/mg and without ocular involvement;
- In groups with high microfilarial load, skin microfilarial density = 10
microfilariae/mg with or without ocular involvement (only in anterior
segment) or skin microfilarial density > 0 and < 10 microfilariae/mg
and with ocular involvement (only in anterior segment), which must
include microfilariae in the eye, i.e. onchocercal corneal opacities
alone are not acceptable.
- iii. For Part 1b:
- positive for microfilariae
3. Body weight at Screening = 40 kg
4. For women of child-bearing potential, acceptance of the requirement to use a highly
effective form of birth control effective from Day 0 until at least 3 months after the
final intake of IMP (Month 4 visit). Choice of birth control method must be clearly
documented.
Exclusion Criteria for Part 1:
1. Participation in any studies other than purely observational studies within 3 months
prior to Screening or during the study, or within 5 times the half-life of the drug in
the previous clinical trial, whichever is longer (time calculated relative to final
intake in previous trial) or currently in the follow-up period for any clinical trial.
2. Any vaccination within 4 weeks prior to IMP administration.
3. Acute infection and/or febrile illness requiring therapy within 14 days prior to IMP
administration.
4. Administration of medication or herbal therapies as follows:
1. Administration of any medication (with the exception of diclofenac, paracetamol,
ibuprofen and aspirin) or herbal preparation within 14 days prior to IMP
administration, or medicine given regularly for an existing condition;
2. The following antifilarial therapies, or medication that may have an antifilarial
effect:
- i. ivermectin; = 6 months prior to IMP administration and / or
- ii. doxycycline; = 1 year prior to IMP administration: more than 2-week
course and / or
- iii. moxidectin; = 2 years prior to IMP administration.
3. Other preventive chemotherapy, e.g. as part of an MDA programme within 14 days
prior to IMP administration.
5. 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.
6. 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.
7. Clinically significant history of cardiac abnormality, and/or relevant pathological
abnormalities on electrocardiography at Screening, such as atrioventricular block (PR
interval above 240 msec), or prolongation of the QRS complex over 120 msec or QTc
interval over 450 msec (QTcB or QTcF).
8. Blood pressure and heart rate in the supine position at Screening, outside one or more
of the ranges 90-140 mmHg systolic, 60-90 mmHg diastolic; heart rate 45-100 beats/min.
9. Symptoms of orthostatic hypotension at Screening, considered clinically significant in
the opinion of the Investigator.
10. History of drug or alcohol abuse.
11. Use of alcohol or drugs of abuse within 48 hours before IMP administration.
12. Abnormal laboratory results at Screening, defined as (based on the reference
laboratory test ranges for the study*):
1. White blood cell count < 3.0 x 109/L
2. Neutrophils < 1.0 x 109 /L
3. Lymphocytes < lower limit of normal (LLN)*
4. Haemoglobin < 11 g/dL
5. Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT)
and/or alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT > 2
x upper limit of normal (ULN*) and/or bilirubin > 1.5 ULN*
6. Fasting glucose > ULN*
7. Potassium < LLN*
8. Serum creatinine > ULN* and estimated Glomerular Filtration Rate (using the
Modification of Diet in Renal Disease equation) < 60 mL/min
9. Any other abnormal laboratory result corresponding to Grade 2 or above in the
study grading criteria, or abnormalities considered significant in the opinion of
the Investigator.
13. History of severe drug allergy, non-allergic drug reactions, severe adverse reaction
to any drug, or multiple drug allergies.
14. Known hypersensitivity to any ingredient of the IMP, including the active ingredient
emodepside, or to ivermectin, or to any medication used during the study (e.g. for eye
examinations).
15. Blood donation within 8 weeks prior to Screening or blood transfusion received within
1 year before Screening.
16. Current hyperreactive onchodermatitis or severe manifestations due to onchocerciasis.
17. Coincidental infection with other endemic filarial parasites based on laboratory tests
at Screening (Wuchereria bancrofti, Mansonella spp.).
18. Coincidental infection with Loa loa based on medical history or positive test at
Screening.
19. In groups intended to include subjects without ocular involvement: ocular
microfilariae or onchocercal eye lesions, assessed at Screening.
20. Ophthalmological history or conditions that could make the ocular examination
difficult or represent a risk for the safety of the subject in the opinion of the
Investigator, assessed at Screening, including the following (subjects will be
excluded if any of the criteria are met for either eye):
1. Ocular disease including inflammatory eye disease, uveitis, glaucoma or evidence
of retinal cysticercosis;
2. History of surgery for glaucoma and/or cataract;
3. Evidence of corneal or conjunctival damage, with or without ocular symptoms
(except corneal opacities in groups intended to include subjects with ocular
involvement);
4. Evidence of an increased risk of acute glaucoma, based on examination of anterior
chamber.
5. Evidence of ocular media opacity, including lens opacity and vitreous opacities,
that make difficult ocular examination in the opinion of the Investigator;
6. Evidence of retinal or optic nerve pathology (including age-related macular
degeneration (AMD));
7. Visual impairment of best corrected or pinhole visual acuity worse than 6/18
metres, and/or visual field defect of grade 3 (on frequency doubling technology
(FDT) or worse; and/or - where ocular coherence tomography (OCT) is used - severe
retinal nerve fibre layer thinning in the superior and inferior quadrant analysis
on OCT of the optic nerve with a corresponding visual field defect of grade 2 (on
FDT) or worse on the same eye; ; or blindness;
8. Any microfilariae identified in the posterior segment of the eye or more than 50
microfilariae in the anterior segment.
21. Unwilling to remain within the clinical research ward for the Admission Period (for
Part 0 and Part 1a), or in or nearby the clinical research ward for the in-house
period (for Part 1b) or unwilling to comply with the house rules of the clinical
research ward.
22. Any other past or current condition that the Investigator feels would exclude the
subject from the study or that places the subject at undue risk.
23. For women of child-bearing potential (WOCBP): pregnancy (determined by date of last
menstrual period and serum pregnancy test prior to first intake of IMP), or
breastfeeding.
24. Unwilling or unable to comply with the requirements of the study protocol for the
entire duration of the study, in the opinion of the Investigator.
25. Unable to participate in the study as per local law, if applicable.
Inclusion Criteria for Part 2:
1. Written, signed (or thumb-printed) and dated informed consent, after having the
opportunity to discuss the trial with the Investigator or a delegate.
2. Men and women with Onchocerca volvulus infection, 18 to 65 years of age inclusive at
time of Screening.
1. Presence of at least 1 excisable subcutaneous nodule/onchocercoma detected on
palpation.
2. Onchocerca volvulus infection diagnosed by skin snip method: documented
mf-positivity on skin assessment on at least 2 out of 4 skin snips.
3. Body weight = 40 kg at Screening.
4. For women of child-bearing potential, acceptance of the requirement to use a highly
effective form of birth control effective from Day 0 until at least 3 months after the
final intake of IMP (Month 4 visit). Choice of birth control method must be clearly
documented.
Exclusion Criteria for Part 2:
1. Participation in any studies other than purely observational studies, within 3 months
prior to Screening, and during the study, or within 5 times the half-life of the drug
tested in the previous clinical trial, whichever is longer (time calculated relative
to last dose in the previous clinical trial) or is currently in the follow-up period
for any clinical trial, or received emodepside as part of a previous clinical trial.
2. Any vaccination within 4 weeks before IMP administration.
3. Acute infection and/or febrile illness requiring therapy within 14 days prior to IMP
administration.
4. Administration of medication or herbal therapies as follows.
1. Administration of any medication (with the exception of diclofenac, paracetamol,
ibuprofen and aspirin) or herbal preparation within 14 days prior to IMP
administration, or medicine given regularly for an existing condition, except
with the approval of the Principal Investigator;
2. The following antifilarial therapies, or medication that may have an antifilarial
effect:
i. ivermectin; = 6 months prior to IMP administration and / or ii. doxycycline; = 1
year prior to IMP administration: more than 2-week course and / or iii. moxidectin; =
2 years prior to IMP administration. c. Other preventive chemotherapy, e.g. as part of
an MDA programme within 14 days prior to IMP administration, except with the approval
of the Principal Investigator.
5. Presence of any of the following at Screening that could interfere with the objectives
of the trial or the safety of the subject, in the opinion of the Investigator:
1. Abnormal physical examination or laboratory finding;
2. Any clinically significant medical condition. Including, but not limited to
diabetes type 1 or 2, significant liver or cardiovascular disease, current or
previous neurological or neuropsychiatric disease or epilepsy, active infection,
sickle cell disease, known human immunodeficiency virus (HIV) infection,
disclosed by review of medical history or concomitant medication.
6. Recent history of drug or alcohol abuse (within 6 months prior to IMP administration).
7. Use of alcohol or drugs of abuse within 24 hours prior to IMP administration.
8. Abnormal laboratory results at Screening, defined as (based on the reference
laboratory test ranges for the study*):
1. Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT)
and/or alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT > 2
x upper limit of normal (ULN*) and/or bilirubin > 1.5 ULN
2. Serum creatinine > ULN* and estimated glomerular filtration rate (using the
Modification of Diet in Renal Disease equation) < 60 mL/min
9. History of severe drug allergy, non-allergic drug reactions, severe adverse reaction
to any drug or multiple drug allergies.
10. Current hyperreactive onchodermatitis.
11. Known hypersensitivity to any ingredient of the IMPs, including the active ingredient
emodepside, or to ivermectin, or to any medication used during the study (e.g. for eye
examination).
12. Blood donation within 8 weeks prior to Screening.
13. Coincidental infection with other endemic filarial parasites based on laboratory tests
at Screening (Wuchereria bancrofti, Mansonella spp.)
14. Coincidental infection with Loa loa based on medical history or positive test at
Screening.
15. Ophthalmological history or conditions that could interfere with the objectives of the
trial or compromise the safety of the subject in the opinion of the Investigator,
assessed at Screening, including the following (subjects will be excluded if any of
the criteria are met for either eye):
1. Inflammatory eye disease, glaucoma, severe uveitis, evidence of retinal
cysticercosis;
2. History of surgery for glaucoma;
3. Severe keratitis, and/or cataracts that interfere with visualisation of the
posterior segment of the eye;
4. Evidence of an increased risk of acute glaucoma, based on examination of anterior
chamber;
5. Evidence of ocular media opacity, including lens opacity and vitreous opacities,
that make difficult ocular examination in the opinion of the Investigator;
6. Evidence of retinal or optic nerve pathology (including age-related macular
degeneration (AMD));
7. Severe visual impairment (best corrected or pinhole visual acuity worse than 6/60
metres), severe reduction of peripheral visual fields (greater than grade 3 on
frequency doubling technology (FDT)) or blindness;
8. Any microfilariae identified in the posterior segment of the eye or more than 50
microfilariae in the anterior segment.
16. Any other past or current condition that the Investigator feels would exclude the
subject from the study or place the subject at undue risk.
17. For women of child-bearing potential (WOCBP): pregnancy (based on date of last
menstrual period, and pregnancy test prior to first intake of IMP) or breastfeeding.
18. Unwilling or unable to comply with the requirements of the study protocol for the
entire duration of the study, in the opinion of the Investigator.
19. Unable to participate in the study as per local law, if applicable.
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