Safety and Efficacy of Novel Combination Regimens for Treatment of Onchocerciasis

Inclusion Criteria: * Adult men and women, 18 years to 75 years old * Participants must have at least 1 palpable subcutaneous nodule (onchocercoma) * Participants with mean skin Mf counts ≥ 1 Mf/mg at the time of enrollment (prior to pretreatment) Exclusion Criteria: * History of treatment with IVM or Mox less than six months prior to pretreatment with IVM. * Treatment with IVM or Mox outside of the study after the pre-treatment clearing dose before treatment with one of the four study treatments. * Pregnant or breastfeeding mothers. * Severe ocular disease at baseline (assessed just prior to the first study treatment, approximately 6-12 months after IVM pretreatment). Briefly, these conditions include severe uveitis, severe glaucoma, severe keratitis, and/or cataracts that interfere with visualization of the posterior segment of the eye. Details regarding ocular exclusion criteria are provided below. Individuals who are excluded with significant ocular disease will be referred for appropriate All ocular disease exclusion criteria apply to either eye. That is to say, participants will be excluded if any of the ocular exclusion criteria listed below are met for either eye. These exclusions are needed to reduce the risk of study treatments worsening severe pre-existing ocular disease. They also are needed to ensure that study staff will be able to adequately evaluate the posterior segment before and after treatment. 1. Any cataract that prevents clear visualization of fundus or imaging by OCT. 2. Severe retinal nerve fiber layer thinning of the optic nerve in the superior and inferior quadrant analysis by OCT with a corresponding visual field defect in the superior and inferior hemifield, and/or visual field loss within 5 degrees of fixation in at least one hemifield. Note: If OCT is not available, the following exclusion criteria will apply: vertical cup/disc ratio by fundoscopy greater than or equal to 0.80 with a corresponding visual field defect in the superior and inferior hemifield, and/or visual field loss within 5 degrees of fixation in at least one hemifield. 3. Intraocular pressure (IOP) greater than or equal to 25 by Goldmann tonometry. 4. Retinal detachment or retinal break. 5. Acute ocular infection (i.e., viral conjunctivitis, corneal ulcer, endophthalmitis). 6. Optic atrophy with a reproducible visual field defect detected by confrontation visual field testing. 7. Exam consistent with Herpes simplex virus eye infection. 8. Homonymous hemianopsia, quadrantopsia, bitemporal hemianopsia, or central scotoma related to cerebral vascular disease by Automated Visual field testing and confrontation visual field testing. 9. Acute angle closure glaucoma. 10. Gonioscopy grade 0 (slit) limiting ability to safely dilate participant. 11. Severe tremor, blepharospasm, or other voluntary or involuntary motor condition that limits careful slit lamp examinations, OCT, gonioscopy, IOP measurement, fundus photography, and automated perimetry. 12. Cognitive impairment that limits participant's ability to understand and perform a Visual Acuity Test with a Tumbling E chart, confrontation visual field, slit lamp exam, or any other ocular exam component. 13. Optic nerve edema. 14. Active retinopathy or retinitis not attributable to onchocercal disease. 15. A history of uveitis not associated with onchocerciasis. 16. Any pre-existing chorioretinal scar or retinal degeneration and other significant retinal pathologies (foveomacular schisis, dystrophies, arterial macroaneurysms etc) involving the macula. 17. Severe ocular pain that the participant rates as 9 or 10 out of 10. 18. Best corrected or pinhole visual acuity worse than 6/60 (20/200). 19. Age-related macular degeneration (AMD). 20. \>5 motile Mf in the anterior chamber in either eye at the time of secondary screening (6 months after pre-treatment with IVM).\* 21. The presence of one or more Mf in the posterior segment of the eye (detected by any opthalmological test performed) at the time of treatment (at least six months after pre-treatment with IVM). \*Note regarding exclusion criteria t and u: The cut-off of 5 Mf in either anterior chamber was suggested by external reviewers of our proposal to the Gates Foundation. These were experts in onchocerciasis selected by the Foundation. The reviews were anonymous, so we do not know their names. They also suggested that we exclude persons with any Mf in the posterior segment of the eye, and we have added that exclusion criterion to the protocol. * Significant comorbidities such as renal insufficiency (creatinine \> 2 times the upper limit of normal), liver disease (jaundice or either AST or ALT greater than 2.5 times the upper limit of normal), or any other acute or chronic illness identified by study clinicians and investigators that interferes with the participant's ability to go to school or work or perform routine household chores. * Prior allergic or hypersensitivity reactions or intolerance to IVM, Mox, ALB, or DEC. * Evidence of severe or systemic comorbidities (aside from features of onchocerciasis), as judged by a study physician. Persons with baseline medical conditions that correspond to adverse event severity scores of grade 3 or higher will also be excluded. * Evidence of urinary tract infection as indicated by 3+ nitrites by dipstick (individuals with 1+ or 2+ nitrites will not be excluded) or underlying chronic kidney disease as indicated by 3+ protein or 3+ blood by dipstick. Persons with urinary tract infections can be enrolled after their infections are treated and cured. * Hgb \<7 gm/dL; any such individuals will be referred to a local health center for evaluation and treatment).