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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Onchocerciasis
• Intervention / Treatment: Drug: Moxidectin; Drug: Ivermectin

• Study Type: Interventional
• Enrollment (Actual): 323
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sally Kinrade; Phone Number: +61 3 9912 2411; Email: sally.kinrade@medicinesdevelopment.com
• Study Contact Backup: Name: Mupenzi Mumbere; Phone Number: +61 3 9912 2428; Email: mupenzi.mumbere@medicinesdevelopment.com

Study Locations

• Congo, The Democratic Republic of the
  • Ituri
    • Rethy, Ituri, Congo, The Democratic Republic of the
      • Centre de Recherche pour les Maladies Tropicales Negligees

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Signs and symptoms of onchocerciasis in all dose groups	Proportion of participants with signs and symptoms of onchocerciasis with these signs and symptoms at baseline.	6 months, 12 months, 18 months, 24 months, 30 months, 36 months
Viability and fertility of male and female macrofilariae in all dose groups	Histopathological assessment of male and female macrofilariae excised from participants with palpable nodules	36 months

Collaborators and Investigators

• Sponsor: Medicines Development for Global Health
• Investigators: Principal Investigator: Tony Ukety, MD, DO, MPH, Centre de Recherche en Maladies Tropicales de l'Ituri

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2021
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: March 11, 2019
• First Submitted That Met QC Criteria: March 14, 2019
• First Posted (Actual): March 15, 2019

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Infections; Parasitic Diseases; Skin Diseases, Parasitic; Skin Diseases, Infectious; Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Filariasis; Onchocerciasis; Anti-Infective Agents; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Ivermectin; Moxidectin
• Other Study ID Numbers: MDGH-MOX-3001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No