Clinical trial NCT03962062: A Pharmacokinetic and Safety Study of Moxidectin to Identify an Optimal Dose for Treatment of Children 4 to 11 Years
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Onchocerciasis
Lead sponsor: Medicines Development for Global Health
Sponsor class: OTHER
First posted: 2019-05-23
Enrollment: 36
Sex: ALL
Minimum age (years): 4
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Area Under the Plasma Concentration Versus Time Curve of Moxidectin.
timeFrame: Pre-dose (Screening) and post-dose at Hours 1, 2, 4, 8, 24 and 72 and Days 7, 14 and 28.
Secondary outcomes:
measure: Area Under the Concentration Versus Time Curve (Zero to Infinity) of Moxidectin
timeFrame: Pre-dose (Screening) and post-dose at Hours 1, 2, 4, 8, 24 and 72, Days 7, 14 and 28 and Week 12.
measure: Maximum Observed Plasma Concentrations (Cmax) of Moxidectin
timeFrame: Pre-dose (Screening) and post-dose at Hours 1, 2, 4 and 8.
measure: Incidence and Severity of Adverse Events.
timeFrame: Day 0 to Week 24 inclusive.
Other outcomes:
Locations:
city: Hohoe
country: Ghana
facility: University of Health and Allied Services School of Public Health
state: Volta Region
Study officials:
affiliation: University of Health and Allied Sciences School of Public Health, Hohoe, Ghana
name: Nicholas O Opoku, MD
role: PRINCIPAL_INVESTIGATOR
References: