Safety and Efficacy of Annual or Biannual Doses of Moxidectin or Ivermectin for Onchocerciasis

Study Overview
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Brief Summary
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The primary purpose of this phase 3b study is to determine the safety and efficacy of moxidectin administration twice a year, compared to once a year, in maintaining undetectable levels in skin of O. volvulus microfilaria in skin, the parasite that causes river blindness. Secondary purposes are to determine the effectiveness of moxidectin compared to ivermectin once or twice a year in maintaining undetectable levels, or reducing levels, of skin microfilaria.

Official Title
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A Randomized, Double Blind, Parallel Trial in the Democratic Republic of Congo (DRC) Comparing the Safety and Efficacy of Annual or Biannual Doses of Moxidectin or Ivermectin for Treatment of Onchocerciasis

Conditions
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Onchocerciasis

Intervention / Treatment
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* Drug: Moxidectin
* Drug: Ivermectin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written informed consent, or assent with parental or guardian written consent. Mean ≥ 10 O. volvulus microfilariae/mg skin, determined by four skin snips Living in a village selected for the study. Age ≥ 12 years. All female participants of childbearing potential must commit to the use of a reliable method of birth control for the duration of treatment and until 3 months after completion of dosing with investigational product. Exclusion Criteria: Pregnant or breast-feeding. Any concurrent condition that, in the opinion of the Investigator, would preclude evaluation of response to treatment or would pose undue risk to the participant's health. Has received ivermectin, oral diethylcarbamazine (DEC) or doxycycline (for > 2 weeks) within 6 months of Baseline. Has received treatment with an investigational agent within the last 30 days (or 5 half-lives, whichever is longer) prior to Baseline. Known or suspected allergy to ivermectin or moxidectin or their excipients. Self-reported planned or ongoing activities within the study period that would make it unlikely that a participant will be available for all planned treatment rounds and follow-up examinations. Weight > 88 kg. Infection with Loa loa.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be assigned to four groups: annual ivermectin; annual moxidectin; biannual ivermectin; or biannual moxidectin
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Annual Moxidectin<br>Moxidectin 8mg per oral, administered annually for 24 months | Drug: Moxidectin<br>* 2mg tablets, encapsulated for blinding<br>|
| Experimental: Biannual Moxidectin<br>Moxidectin 8mg per oral, administered biannually for 24 months | Drug: Moxidectin<br>* 2mg tablets, encapsulated for blinding<br>|
| Active Comparator: Annual Ivermectin<br>Ivermectin (approximately) 150 micrograms/kg per oral, administered annually for 24 months | Drug: Ivermectin<br>* 3mg tablets, encapsulated for blinding<br>|
| Experimental: Biannual Ivermectin<br>Ivermectin (approximately) 150 micrograms/kg per oral, administered biannually for 24 months | Drug: Ivermectin<br>* 3mg tablets, encapsulated for blinding<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of moxidectin annual and biannual recipients with sustained microfilarial response at month 12 | Proportion of recipients with zero Onchocerca volvulus microfilariae/mg skin at all post-treatment timepoints to month 12 | Up to 12 months | 
| Incidence and severity of adverse events | Incidence and severity of adverse events, vital signs and liver function tests | Up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants in all dose groups with sustained microfilariae response | Proportion of participants with zero Onchocerca volvulus microfilariae/mg skin | 6 months, 12 months, 18 months, 24 months, 30 months, 36 months | 
| Sustained ocular microfilariae response in all dose groups | Proportion of participants with 0 live O. volvulus microfilariae in the anterior chambers of the eyes at all post-Baseline assessments in those with liver ocular microfilariae before the first treatment | 6 months, 12 months, 18 months, 24 months, 30 months, 36 months | 
| Skin microfilarial density in all dose groups | Mean, median and percentage reduction Onchocerca volvulus microfilariae/mg skin from baseline | 6 months, 12 months, 18 months, 24 months, 30 months, 36 months | 
| Ocular microfilariae response in all dose groups | Proportion of participants in all dose groups with 0 Onchocerca volvulus microfilariae/mg skin and 0 live microfilariae in the anterior chambers of the eyes each timepoint | 6 months, 12 months, 18 months, 24 months, 30 months, 36 months | 
| Mean skin microfilariae density at each post-Screening assessment | Mean and mean change from baseline of Onchocerca volvulus microfilariae/mg skin | 6 months, 12 months, 18 months, 24 months, 30 months, 36 months |