A Pharmacokinetic and Safety Study of Moxidectin to Identify an Optimal Dose for Treatment of Children 4 to 11 Years

Study Overview
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Brief Summary
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The primary purpose of this study is to determine a dose of moxidectin for children 4 to 11 years that is equivalent to an 8 mg dose administered for treatment of onchocerciasis in people 12 years and over. The secondary purpose is to evaluate the safety and pharmacokinetics of a single dose of moxidectin in children and adolescents aged 4 to 17 years.

Official Title
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An Open-label Study of the Pharmacokinetics and Safety of a Single Dose of Moxidectin Per Oral in Subjects Aged 4 to 17 Years With (or at Risk of) Onchocerciasis to Identify an Optimal Dose for Treatment of Children 4 to 11 Years

Conditions
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Onchocerciasis

Intervention / Treatment
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* Drug: Moxidectin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 4 to 17 years, inclusive: Cohort I: 12 to 17 years; Cohort II: 8 to 11 years; Cohort III: 4 to 7 years; Live in a region designated by the World Health Organization (WHO) as endemic for O. volvulus infection (World Health Organization, 2019). Specifically, participants will be recruited from the Kpassa sub-district of the Nkwanta North district.The specific communities will include Wii, Jagri-Do, and Azua where mass drug administration with ivermectin for onchocerciasis commenced in October 2017; Willing and able to remain at the study clinic from Screening up to Day 7; Provision of parental or guardian written informed consent and assent / lack of expression of 'deliberate objection' (as appropriate for age); Females of childbearing potential must commit to using a reliable method of contraception as per local family planning guidelines from Baseline (pre-treatment on Day 0) until approximately 6 months after treatment with study drug. Exclusion Criteria: History of serious medical or psychiatric condition which, in the opinion of the investigator, would put the subject at increased risk by participating in the study or jeopardize study outcomes; Known or suspected concurrent clinically significant renal, cardiac, pulmonary, vascular, metabolic (thyroid disorders, adrenal disease), immunological disorders or malignancy, congenital heart disease, chronic lung disease; Has received an investigational product within 28 days or 5 half-lives of Baseline, whichever is longer; Has received ivermectin or any other anti-helminthic treatments within 28 days of Baseline; Has received a vaccination within 7 days of Baseline; Known or suspected hypersensitivity to macrocyclic lactones or excipients used in the formulation of moxidectin; Poor venous access; Unable to swallow tablets (flat oval, 8.0 millimeters (mm) x 4.5 mm x 3.0 mm); Weight: Cohort I (12 to 17 years): < 30 kg; Cohort II (8 to 11 years): < 18 kg; Cohort III (4 to 7 years): < 12 kg; Clinically relevant laboratory abnormalities at Screening, including: Hemoglobin < 9.5 grams per deciliter (g/dL); Neutrophil (granulocyte) count < 1.5 x 109/L; Platelet count < 110 x 109/L; Alanine aminotransferase (ALT) > 1.5 times the upper limit of normal range (ULN); Total bilirubin > 1.5 times ULN; Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV) positive; Known or suspected malaria or other ongoing viral, bacterial, or plasmodium infection at Screening and/or Baseline; Loa loa co-infection; Unwilling, unlikely or unable to comply with all protocol specified assessments; For females of child bearing potential, pregnant or breastfeeding, or planning to become pregnant; Previous enrolment in this study; Is a sibling of another child already enrolled in this study.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 17 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: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Prospective, age-stratified, adaptive, open-label, single-dose study with 3, age-defined cohorts. Cohort 1 (12 to 17 years, n = 9) and Cohort 2 (8 to 11 years, n = 9) will receive moxidectin 8 mg. Cohort 3 (4 to 7 years, n = 9) will receive moxidectin at a dose to be determined from safety and pharmacokinetic data analyses of Cohorts 1 and 2. If the starting dose for Cohorts 2 and 3 results in at least 3 subjects with moxidectin exposures above the target range, a revised dose will be determined in decrements of 2 mg and the Cohort(s) will be repeated with at least 9 new subjects. For Cohort 3, if the starting dose results in at least 3 subjects with moxidectin exposures below the target range, a revised dose will be determined in increments of 2 mg to a maximum dose of 8 mg.Therefore, it is expected that the study will enroll 27 subjects. However, if additional cohorts are required to meet pharmacokinetic outcomes, up to a maximum of 63 subjects may be enrolled.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: 12-17 years<br>Moxidectin 8mg per oral, single dose | Drug: Moxidectin<br>* 2 mg tablets<br>|
| Experimental: Cohort 2: 8-11 years<br>Moxidectin 8mg (or lower dose) per oral, single dose | Drug: Moxidectin<br>* 2 mg tablets<br>|
| Experimental: Cohort 3: 4-7 years<br>Moxidectin single dose, determined by population pharmacokinetic modelling including data from Cohorts 1 and 2 | Drug: Moxidectin<br>* 2 mg tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve of moxidectin | Moxidectin concentration in plasma collected at pre-specified intervals after dosing with oral moxidectin determined using a validated liquid chromatography-mass spectrometry(MS)/MS method. | Pre-dose to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration versus time curve (zero to infinity) of moxidectin | Moxidectin concentration in plasma collected at pre-specified intervals after dosing with oral moxidectin determined using a validated liquid chromatography-mass spectrometry(MS)/MS method. | Pre-dose to Week 12 | 
| Maximum observed plasma concentrations (Cmax) of moxidectin | Moxidectin concentration in plasma collected at pre-specified intervals after dosing with oral moxidectin determined using a validated liquid chromatography-mass spectrometry(MS)/MS method. | Hour 0 to Hour 8 | 
| Incidence and severity of adverse events | Incidence and severity of adverse events, assessed by the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Paediatric Adverse Events, Version 2.1. | Day 0 to Week 24 |