Emodepside Phase II Trial for Treatment of Onchocerciasis

NCT05180461 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: DNDi-EMO-04UHAS-REC A.1 [1] 20-21
• Study Type: interventional
• Target: 578
• Locations: 2 countries
• Sites: 3

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.

Conditions

Onchocerciasis

Keywords

Helminthiasis; Filariasis; Parasitic diseases; Nematode Infections; Neglected tropical diseases; Skin Diseases, Parasitic; Skin Diseases, Infectious; River blindness; Anthelmintics; Anti-Infective Agents; Antinematodal Agents; Skin diseases; Anti-parasitic agents; Octadepsipeptide (cyclic depsipeptide)

Outcome Measures

Primary Outcomes (3)

• Part 1 - absence (or presence) of live female adult worms with normal embryogenesis

  Absence (or presence) of live female adult worms with normal embryogenesis, assessed by histological examination of nodules collected on nodulectomy

  12 months

• Part 1 - absence (or presence) of skin microfilariae (co-primary outcome)

  Absence (or presence) of skin microfilariae across four skin snips

  12 months

• Part 2 - absence (or presence) of skin microfilariae

  Absence (or presence) of skin microfilariae, assessed across all skin snips in a participant

  24 months

Secondary Outcomes (11)

• Part 1- absence (or presence) of live female adult worms

  12 months

• Part 1 - presence (or absence) of dead female adult worms

  12 months

• Part 1 - Absence (or presence) of skin microfilariae

  up to 12 months

• Part 1 - reduction in skin microfilarial density

  up to 12 months

• Part 1 - Absence (or presence) of microfilariae in nodular tissue

  12 months

Study Arms (9)

Part 0 Pilot group emodepside 15mg Once a day (OD) 1 day

EXPERIMENTAL

emodepside tablets 15 milligrams once a day for 1 day

Drug: emodepside

Part 1 emodepside 30mg OD 1 day

EXPERIMENTAL

emodepside tablets 30 milligrams once a day for 1 day

Drug: emodepside

Part 1 emodepside 15mg OD 7 days

EXPERIMENTAL

emodepside tablets 15 milligrams once a day for 7 days

Drug: emodepside

Part 1 emodepside 15mg OD 14 days

EXPERIMENTAL

emodepside tablets 15 milligrams once a day for 14 days

Drug: emodepside

Part 1 emodepside 15mg twice a day (BID) 10 days

EXPERIMENTAL

emodepside tablets 15 milligrams twice a day for 10 days

Drug: emodepside

Part 1 placebo

PLACEBO COMPARATOR

matching placebo of emodepside tablets

Drug: matching placebo of emodepside

Part 2 emodepside dose regimen A

EXPERIMENTAL

emodepside tablets, dose regimen A selected from regimens tested in Part 1

Drug: emodepside; Drug: matching placebo of ivermectin

Part 2 emodepside dose regimen B

EXPERIMENTAL

emodepside tablets, dose regimen B selected from regimens tested in Part 1

Drug: emodepside; Drug: matching placebo of ivermectin

Part 2 ivermectin

ACTIVE COMPARATOR

ivermectin, single oral dose of 150 micrograms per kilogram by weight

Drug: matching placebo of emodepside; Drug: ivermectin

Interventions

emodepside DRUG

emodepside tablet

Also known as: BAY 44-4400

Part 0 Pilot group emodepside 15mg Once a day (OD) 1 day; Part 1 emodepside 15mg OD 14 days; Part 1 emodepside 15mg OD 7 days; Part 1 emodepside 15mg twice a day (BID) 10 days; Part 1 emodepside 30mg OD 1 day; Part 2 emodepside dose regimen A; Part 2 emodepside dose regimen B

matching placebo of emodepside DRUG

emodepside matching placebo tablet

Part 1 placebo; Part 2 ivermectin

ivermectin DRUG

ivermectin tablet (overencapsulated for blinding)

Also known as: Mectizan, Stromectol

Part 2 ivermectin

matching placebo of ivermectin DRUG

matching placebo of overencapsulated ivermectin tablet

Part 2 emodepside dose regimen A; Part 2 emodepside dose regimen B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written, signed (or thumb-printed) and dated informed consent, after having the opportunity to discuss the study with the Investigator or a delegate.
• Men and women with Onchocerca volvulus infection, 18 to 65 years of age inclusive at time of Screening,
• Presence of at least 1 excisable subcutaneous nodule/onchocercoma detected on palpation
• 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
• Body weight at Screening ≥ 40 kg
• 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.

You may not qualify if:

• 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.
• Any vaccination within 4 weeks prior to IMP administration.
• Acute infection and/or febrile illness requiring therapy within 14 days prior to IMP administration.
• Administration of medication or herbal therapies as follows:
• 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;
• 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.
• Other preventive chemotherapy, e.g. as part of an MDA programme within 14 days prior to IMP administration.
• 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.
• 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.
• 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).
• 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.
• Symptoms of orthostatic hypotension at Screening, considered clinically significant in the opinion of the Investigator.

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead
• Bayer: collaborator

Study Sites (3)

Centre de santé de référence de Kimpese

Kimpese, Bas-Congo Province, Democratic Republic of the Congo

Location

Hôpital général de référence de Masimanimba

Masi-Manimba, Kwilu, Democratic Republic of the Congo

Location

University of Health and Allied Services School of Public Health

Hohoe, Volta Region, Ghana

Location

MeSH Terms

Conditions

Onchocerciasis; Helminthiasis; Filariasis; Parasitic Diseases; Nematode Infections; Neglected Diseases; Skin Diseases, Parasitic; Skin Diseases, Infectious; Onchocerciasis, Ocular; Skin Diseases

Interventions

emodepside; Bay 44-4400; Ivermectin

Condition Hierarchy (Ancestors)

Spirurida Infections; Secernentea Infections; Infections; Skin and Connective Tissue Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Eye Infections, Parasitic; Vector Borne Diseases; Eye Infections; Eye Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Masking applies to Parts 1a/b and Part 2. Part 0 (Pilot Group) is Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2020
• First Posted: January 6, 2022
• Study Start: August 30, 2021
• Primary Completion (Estimated): September 18, 2026
• Study Completion (Estimated): October 2, 2026
• Last Updated: March 5, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Within 12 months of Clinical Study report finalization
• Access Criteria: Open Access

Locations

DE (2); GH (1)