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

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

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.

Inclusion Criteria:

1. Aged 4 to 17 years, inclusive:

   1. Cohort I: 12 to 17 years;
   2. Cohort II: 8 to 11 years;
   3. Cohort III: 4 to 7 years;

2. 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;

3. Willing and able to remain at the study clinic from Screening up to Day 7;

4. Provision of parental or guardian written informed consent and assent / lack of expression of 'deliberate objection' (as appropriate for age);

5. 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:

1. 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;

2. 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;

3. Has received an investigational product within 28 days or 5 half-lives of Baseline, whichever is longer;

4. Has received ivermectin or any other anti-helminthic treatments within 28 days of Baseline;

5. Has received a vaccination within 7 days of Baseline;

6. Known or suspected hypersensitivity to macrocyclic lactones or excipients used in the formulation of moxidectin;

7. Poor venous access;

8. Unable to swallow tablets (flat oval, 8.0 millimeters (mm) x 4.5 mm x 3.0 mm);

9. Weight:

   1. Cohort I (12 to 17 years): < 30 kg;
   2. Cohort II (8 to 11 years): < 18 kg;
   3. Cohort III (4 to 7 years): < 12 kg;

10. Clinically relevant laboratory abnormalities at Screening, including:

    1. Hemoglobin < 9.5 grams per deciliter (g/dL);
    2. Neutrophil (granulocyte) count < 1.5 x 109/L;
    3. Platelet count < 110 x 109/L;
    4. Alanine aminotransferase (ALT) > 1.5 times the upper limit of normal range (ULN);
    5. Total bilirubin > 1.5 times ULN;

11. Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV) positive;

12. Known or suspected malaria or other ongoing viral, bacterial, or plasmodium infection at Screening and/or Baseline;

13. Loa loa co-infection;

14. Unwilling, unlikely or unable to comply with all protocol specified assessments;

15. For females of child bearing potential, pregnant or breastfeeding, or planning to become pregnant;

16. Previous enrolment in this study;

17. Is a sibling of another child already enrolled in this study.