Onchocerca Infection, Onchocercal Subcutaneous Nodule, Onchocerciasis, Onchocerciasis, Ocular, Tropical Disease
Conditions
Brief summary
This study will investigate the safety and effectiveness of combination regimens in persons with onchocerciasis when it is administered after pre-treatment with ivermectin to clear or greatly reduce microfilariae from the skin and eyes.
Detailed description
The open label, randomized clinical trial studies the safety and efficacy of combination regimens for the treatment of onchocerciasis. Around 300 participants from Bong Mines, Liberia will be randomly assigned to one of four treatment groups after receiving Ivermectin pre-treatment: Ivermectin plus Albendazole (IA0, Ivermectin plus DEC plus Albendazole (IDA), Moxidectin plus albendazole (MoxA), or Moxidectin plus DEC plus Albendazole (MoxDA). Participants will be treated at baseline and 6 months after initial treatment. Safety will be measured through extensive adverse event monitoring from baseline to 6 months. Efficacy of the treatment will be measured at 24 months after the initial treatment by the proportion of all adult female worms that are fertile in the Onchocerca nodules and the percentage of participants without microfilaremia at 6, 18, and 24 months after the first treatment.
Interventions
DRUGIvermectin w/ Albendazole
Participants will be given a dose of oral Ivermectin (IVM) (150 µg/kg) plus Albendazole (ALB) (400 mg)
DRUGIvermectin + Diethylcarbamazine + Albendazole
Participants will be given a dose of oral Ivermectin (IVM) (150 µg/kg), Diethylcarbamazine (DEC) (6 mg/kg) and Albendazole (ALB) (400 mg)
DRUGMoxidectin + Albendazole
Participants will be given a dose of oral Moxidectin (Mox) (8 mg) plus Albendazole (ALB) (400 mg)
DRUGMoxidectin + Diethylcarbamazine + Albendazole
Participants will be given a dose of oral Moxidectin (Mox) (8 mg), Diethylcarbamazine (DEC) (6 mg/kg) and Albendazole (ALB) (400 mg)
Sponsors
National Public Health Institute of Liberia
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Intervention model description
IVM + ALB (IA) - Dose of oral IVM (150 µg/kg) plus ALB (400 mg) Mox + ALB (MoxA) - Dose of oral Mox (8mg tablets) plus ALB (400mg) IVM + DEC + ALB (IDA) - Dose of oral IVM (150 µg/kg), DEC (6 mg/kg) and ALB (400 mg) MOX + DEC + IVM (MoxDA) - Dose of oral Mox (8 mg), DEC (6 mg/kg) and ALB (400 mg)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rates and types of severe or serious adverse events within 6 months following Ivermectin treatments | Baseline to 6 months | Rates and types of severe or serious adverse events (grade 3 or higher) occurring within 6 months following combination treatment with DEC, ivermectin, and albendazole (IDA) vs. the comparator regimen of ivermectin plus albendazole (IA). |
| Rates and types of severe or serious adverse events within 6 months following Moxidectin treatments | Baseline to 6 months | Rates and types of severe or serious adverse events (grade 3 or higher) occurring within 6 months following combination treatment with DEC, moxidectin, and albendazole (MoxDA) vs. the comparator regimen of moxidectin plus albendazole (MoxA). |
| Proportion of all adult female worms that are fertile 24 months after first treatment | 24 months | Proportion of all adult female worms in nodules that are fertile (i.e. with morulae or later developmental stages in the uterus) 24 months after the first treatment dose. The primary objective efficacy analysis will be restricted to comparisons between IA vs IDA and between MoxA vs. MoxDA, respectively. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rates of adverse events grade 3 or higher in participants with ocular MF in Moxidectin treatment groups. | Baseline to 7 days after first treatment. | Rates of adverse events grade 3 or higher that occur within 7 days of treatment in participants with detectable intraocular microfilariae just before the study treatment. |
| Rates of ocular adverse events (any grade) by Ivermectin treatment group | Baseline to 7 days after first treatment. | To compare rates of ocular adverse events (any grade) by treatment group that occur within 7 days of treatment. Comparison is between IA vs IDA. |
| Rates of ocular adverse events (any grade) by Moxidectin treatment groups | Baseline to 7 days after first treatment. | To compare rates of ocular adverse events (any grade) by treatment group that occur within 7 days of treatment. Comparison is between MoxA vs MoxDA. |
| Percentage of adult female worms in nodules that are alive | 24 Months | Percentage of adult female worms in nodules that are alive 24 months after the first round of study treatment. |
| Percentage of nodules with microfilaria in tissue | 24 Months | The percentage of nodules with microfilariae in nodule tissue (outside of worms) |
| Rates of adverse events grade 3 or higher by Ivermectin treatment group, that occur within 7 days of treatment | Baseline to 7 days after first treatment. | Rates of adverse events grade 3 or higher by treatment group, that occur within 7 days of treatment. Comparison is made between IA vs IDA. |
| Percentage of participants without microfiladermia after the first study treatment. | 6, 18, and 24 Months | Percentage of participants without microfiladermia at 6, 18 and 24 months after the first study treatment. |
| Percentage of participants with recurrence of microfilariae in the skin across treatment groups | 18 and 24 Months | Percentage of participants with recurrence of microfilariae in the skin at 18 and 24 months after the first study treatment (among persons who had complete Mf clearance 6 months after the first study treatment). |
| Microfilariae density in the skin across treatment groups | 6, 8, and 24 Months | Mf density in the skin at 6, 18, and 24 months after the first study treatment. |
| Percentage of nodules with fully or partially calcified worms | 24 Months | Percentage of nodules with fully or partially calcified worms 24 months after the first round of study treatment. |
| Percentage of nodules that do not contain living adult worms | 24 Months | The percentage of nodules that do not contain any living adult female worms |
| Rates of adverse events grade 3 or higher by Moxidectin treatment group, that occur within 7 days of treatment | Baseline to 7 days after first treatment. | Rates of adverse events grade 3 or higher by treatment group, that occur within 7 days of treatment. Comparison is made between MoxA vs MoxDA. |
| Rates of adverse events grade 3 or higher in participants with ocular MF in Ivermectin treatment groups. | Baseline to 7 days after first treatment. | Rates of adverse events grade 3 or higher that occur within 7 days of treatment in participants with detectable intraocular microfilariae just before the study treatment. |
Countries
Liberia
Outcome results
None listed