Safety and Efficacy of IDA for Onchocerciasis
Condition: Onchocerciasis
MeSH terms: Onchocerciasis
Intervention: IVM w/ ALB; Single dose of IDA; Three daily doses of IDA
Intervention description: Participants will be given a single dose of oral IVM (150 µg/kg) plus ALB (400 mg) (IVM/ALB); Participants will be given a single dose of oral IVM (150 µg/kg), DEC (6 mg/kg) and ALB (400 mg); Participants will be given one daily dose for 3 days of oral IVM (150 µg/kg), DEC (6 mg/kg) and ALB (400 mg)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants will be split into two strata - those without ocular Mf detected six months after ivermectin pretreatment in the Part I preceding study AND without ocular Mf detected at baseline in the part II study will be in stratum 1. Those participants with ocular Mf detected 6 months after ivermectin pretreatment in the preceding study OR with ocular Mf detected at the baseline exam for this study will be in stratum 2. Stratum 1 will be enrolled first, followed by stratum 2. Members of each stratum will be evenly randomized into one of three treatment arms:
IVM + ALB - Single dose of oral IVM (150 µg/kg) plus ALB (400 mg) (IVM/ALB)
IDA x 1 dose - Single dose of oral IVM (150 µg/kg), DEC (6 mg/kg) and ALB (400 mg)
IDA x 3 doses -Once daily for 3 days oral IVM (150 µg/kg), DEC (6 mg/kg) and ALB (400 mg)
Masking: None (Open Label)
Masking description: While this is an open label study and there is no placebo treatment group, all efforts will be made to ensure that that medical/technical staff assessing skin Mf, adverse events (AEs) and ophthalmological findings will be unaware of initial baseline skin and ocular Mf findings and treatment arm as best as possible.
Enrollment: 154.0
Sex: All
Minimum age: 16 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: ophthalmology

Summary:

      This DOLF study will investigate the safety and effectiveness of IDA treatment in persons
      with onchocerciasis when it is administered after pre-treatment with ivermectin to clear or
      greatly reduce microfilariae from the skin and eyes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women who were previously enrolled in the preceding Part I study (Protocol
             ID#201804116) and residing in the study area

          -  Must have at least palpable subcutaneous nodule (onchocercoma)

          -  Participants with baseline skin Mf counts less than or equal to 3 Mf/mg at the time of
             enrollment into the Part I study (Protocol ID#201804116)

        Exclusion Criteria:

          -  Pregnant and breastfeeding mothers within 1 month of giving birth

          -  Severe eye disease at baseline including uveitis, severe glaucoma, severe keratitis,
             and/or cataracts that interfere with visualization of the posterior segment of the eye
             as well as the list of ocular diseases as outlined below. All ocular disease exclusion
             criteria apply to either eye. Bilateral disease is not necessary to exclude a
             participant. A participant will be excluded if any of the criteria are met for one
             eye.

               1. Any cataract of any type preventing clear visualization of fundus or imaging on
                  Optical Coherence Tomography (OCT).

               2. Severe retinal nerve fiber layer thinning in the superior and inferior quadrant
                  analysis on Ocular Coherence Tomography of the optic nerve with a corresponding
                  visual field defect of grade 2 or worse on the same eye.If Ocular Coherence
                  Tomography is not available, the following exclusion criteria will apply:
                  vertical Cup/disc ratio on fundoscopy (not by OCT reading) greater than or equal
                  to 0.80.

               3. Intraocular pressure (IOP) greater than or equal to 25 by Goldmann tonometry .12

               4. Retinal Detachment or Retinal Break

               5. Acute ocular infection (i.e., Viral conjunctivitis, corneal ulcer,
                  endophthalmitis)

               6. Optic Atrophy with visual field defect reproducible on confrontation visual field
                  testing..

               7. Exam consistent with Herpes Simplex Virus eye infection

               8. Homonymous hemianopsia, quadrantanopsia, 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 patient

              11. Severe Tremor, blepharospasm, or other voluntary or involuntary motor condition
                  that prevents ability to examine patient with slit lamp, OCT, gonioscopy, IOP
                  measurement, fundus photography, and Frequency doubling technology perimetry.

              12. Cognitive impairment sufficient to prevent ability to understand and perform
                  Visual Acuity Test with 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. History of uveitis not associated with onchocercal disease

              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 patient rates as 9 or 10 out of 10 pain.

              18. Best corrected or pinhole visual acuity worse than 6/60 (20/200)

              19. Age related macular degeneration (AMD)

          -  Significant comorbidities such as renal insufficiency, liver failure, 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 / hypersensitivity reactions or intolerance to IVM, ALB, or DEC.

          -  Treatment with IVM outside of the study after the pre-treatment clearing dose provided
             in the Part I study.

          -  >5 motile Mf in the anterior chamber in either eye at the time of enrollment (after
             pre-treatment with IVM).

          -  Any Mf identified in the posterior segment of the eye at the time of enrollment (six
             months after pre-treatment with IVM).

          -  Any other condition identified by study clinicians or investigators that may preclude
             participation in the study.