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

• Sponsor: Medicines Development for Global Health (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03962062
• Collaborator: (none)
• Enrollment: 27
• Location: 1
• Arms: 3
• Anticipated Duration (Months): 17.1
• Patients Per Site Per Month: 1.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Onchocerciasis	Drug: Moxidectin	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 27 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• 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.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)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Mar 29, 2021
• Actual Primary Completion Date: May 30, 2022
• Anticipated Study Completion Date: Sep 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Area under the plasma concentration versus time curve of moxidectin [Pre-dose to Day 28]

   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.

Secondary Outcome Measures

1. Area under the concentration versus time curve (zero to infinity) of moxidectin [Pre-dose to Week 12]

   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.

2. Maximum observed plasma concentrations (Cmax) of moxidectin [Hour 0 to Hour 8]

   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.

3. Incidence and severity of adverse events [Day 0 to Week 24]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Aged 4 to 17 years, inclusive:

2. Cohort I: 12 to 17 years;

3. Cohort II: 8 to 11 years;

4. Cohort III: 4 to 7 years;

5. 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;

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

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

8. 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:

10. Cohort I (12 to 17 years): < 30 kg;

11. Cohort II (8 to 11 years): < 18 kg;

12. Cohort III (4 to 7 years): < 12 kg;

13. Clinically relevant laboratory abnormalities at Screening, including:

14. Hemoglobin < 9.5 grams per deciliter (g/dL);

15. Neutrophil (granulocyte) count < 1.5 x 109/L;

16. Platelet count < 110 x 109/L;

17. Alanine aminotransferase (ALT) > 1.5 times the upper limit of normal range (ULN);

18. Total bilirubin > 1.5 times ULN;

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

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

21. Loa loa co-infection;

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

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

24. Previous enrolment in this study;

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Health and Allied Services School of Public Health	Hohoe	Volta Region	Ghana

Sponsors and Collaborators

• Medicines Development for Global Health

Investigators

• Principal Investigator: Nicholas O Opoku, MD, University of Health and Allied Sciences School of Public Health, Hohoe, Ghana

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Jul 3, 2020

More Information

Publications

None provided.

• Responsible Party: Medicines Development for Global Health
• ClinicalTrials.gov Identifier: NCT03962062
• Other Study ID Numbers: MDGH-MOX-1006
• First Posted: May 23, 2019
• Last Update Posted: Jun 8, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Onchocerciasis; Moxidectin

Study Results

No Results Posted as of Jun 8, 2022