Onchocerciasis
Conditions
Interventions
Part 1 Arm A ABBV 4083
Part 1 Arm B ABBV 4083
Part 1 Arm C ABBV 4083 and albendazole
Part 1 Arm D ABBV 4083 and albendazole
Part 1 Arm E albendazole
Part 2 Basic Arm K ABBV 4083 plus or minus albendazole plus ivermectin
Part 2 Basic Arm L ABBV 4083 plus or minus albendazole
Part 2 Basic Arm M ABBV 4083 plus or minus albendazole plus or minus ivermectin
Part 2 Basic Arm N1 Placebo and Ivermectin
Sponsors
Drugs for Neglected
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written, signed (or thumb-printed) and dated informed consent. 2. Men and women with Onchocerca volvulus infection, 18 to 65 years of age inclusive at time of Screening: i. Presence of at least one excisable subcutaneous nodule/onchocercoma detected on palpation; ii. O. 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 requirement to use highly effective birth control from Day 0 until at least 1 month after the final intake of IMP.
Exclusion criteria
Exclusion criteria: Main exclusion criteria 1. Administration of medication or herbal preparations as follows: i. Any medication or herbal preparation within 14 days prior to IMP administration; ii. Strong CYP3A inhibitors or inducers within 14 days or 10 half-lives, whichever is longer, prior to IMP administration. iii. Other drugs known to interact with albendazole, within 14 days or 10 half-lives, whichever is longer, prior to IMP administration; iv. 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-week course; and/or • any other anti-Wolbachia treatments, = 1 year prior to IMP administration: more than 2-week course; and/or • moxidectin, = 2 years prior to IMP administration; v. Other preventive chemotherapy, e.g. as part of an MDA program, within 14 days prior to IMP administration; 2. Requirement for albendazole during the first 28 days after IMP administration or more than one dose per year thereafter given in MDA; 3. Presence of any of the following at Screening: i. Abnormal physical and/or neurological examination or laboratory findings; ii. Any clinically significant medical condition including, significant acute or chronic liver or kidney condition or cardiovascular disease, active infection, current or previous epilepsy, known human immunodeficiency virus (HIV) infection, disclosed by review of medical history or concomitant medication; 4. Ophthalmological history or conditions that could interfere with the objectives of the trial or the safety of the subject. 5. Clinically significant history of cardiac abnormality, and/or relevant pathological abnormalities on the ECG at Screening. 6. Known hypersensitivity to any ingredient of the IMPs, including the active ingredient of ABBV-4083, macrolides, albendazole or to ivermectin or to any medication used during the study (e.g. for eye examination). 7. Coincidental infection with other endemic filarial parasite (Loa loa > 8 000 mf/mL, Mansonella species or Wuchereria bancrofti), based on positive laboratory test at Screening. 8. Current hyperreactive onchodermatitis or severe manifestation due to onchocerciasis. 9. For women of child-bearing potential: pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1. Status of each live female adult worm as without Wolbachia endobacteria or not, as assessed by immunohistology of nodules;Part 2. Status of each subject as without skin microfilariae or not, as assessed across all skin snips in subject | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 1. Proportion of live female adult worms with only degenerated embryos in the uterus per subject ;Part 1. Proportion of live female adult worms out of all female adult worms per subject ;Part 1. Absence of microfilariae in nodular tissue per subject ;Part 1. Status of each subject as without skin microfilariae or not;Part 1. Reduction in skin microfilarial density (defined as mean number of microfilariae/mg per subject) as compared to baseline;Part 1. Status of each live adult worm as without Wolbachia endobacteria or not, as assessed by PCR;Part 2. Proportion of live female adult worms per subject;Part 2. Proportion of live female adult worms with only degenerated embryos in uterus per subject ;Secondary efficacy Part 2. Status of each subject as without skin microfilariae or not at all;Secondary efficacy Part 2. Reduction in skin microfilarial density as compared to baseline;Secondary efficacy Part 2. Absence of microfilariae in nodular tissue per subject ;Secondary efficacy Part 2. Status of each live adult female worm as without Wolbachia endobacteria or not, assessed by immunohistology;Secondary efficacy Part 2. Status of each live adult worm as without Wolbachia endobacteria or not, as assessed by PCR;Exploratory Parts 1 and 2. Absence of Wolbachia in skin microfilariae per subject, as assessed by PCR;Exploratory Parts 1 and 2. Decline in number of Wolbachia in skin microfilariae per subject compared to baseline, as assessed by PCR;Exploratory Parts 1 and 2. Microfilaria levels in cornea and anterior chamber per subject;Exploratory Parts 1 and 2. Presence, severity and clinical evolution of onchocerciasis ocular disease and onchocerciasis skin disease in each subject;Safety Parts 1 and 2. Adverse events, physical and skin examination findings, vital signs, ECG, clinical laboratory parameters including haematology, biochemistry, urine analysis and ophthalmological analysis;Pharmacokinetic Part 1 ABBV 4083 and albendazole sulfoxide AUCtau, | — |
Countries
Congo
Contacts
Public ContactVirginie Pillet
Clinical Project Manager
Outcome results
None listed