Study Evaluating Orally Administered Moxidectin In Subjects With Onchocerca Volvulus Infection

A Randomized, Single-Ascending Dose, Ivermectin-Controlled, Double-Blind, Safety, Tolerability, Pharmacokinetic, and Efficacy Study Of Orally Administered Moxidectin In Subjects With Onchocerca Volvulus Infection

The primary purpose of this study was to determine the safety and tolerability of moxidectin in subjects infected with Onchocerca volvulus (a parasitic worm).

Study Overview

• Status: Completed
• Conditions: Onchocerciasis
• Intervention / Treatment: Drug: 2 mg moxidectin; Drug: ivermectin 150 mcg/kg; Drug: 4 mg moxidectin; Drug: 8 mg moxidectin

Detailed Description

This was a phase 2, randomized, ivermectin-controlled, double-blind, single-ascending-dose, parallel design, inpatient/outpatient study of moxidectin administered to subjects of both sexes with different degrees of severity of O. volvulus infection. The study was conducted at a single site in Ghana.

Secondary objects are to determine the pharmacokinetics of moxidectin, to obtain initial indication of the efficacy in terms of long term effect on skin microfilaria levels and an indication of the effect on the macrofilaria that may underlie the effect on skin microfilaria levels.

Subjects were enrolled in consecutive cohorts to receive a single oral dose of 2 mg, 4 mg or 8 mg or moxidectin or ivermectin 150 µg/kg by severity of infection, based on the mean of the skin microfilariae densities at each of 4 body locations, both iliac crests and calves.

• Study Type: Interventional
• Enrollment (Actual): 172
• Phase: Phase 2

Contacts and Locations

Study Locations

• Ghana
  • Volta Region
    • Hohoe, Volta Region, Ghana
      • Onchocerciasis Chemotherapy Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written, signed (or thumb-printed), and dated informed consent
2. Aged 18 to 60 years, inclusive
3. Body weight ≥ 40 kg for women and ≥ 45 kg for men
4. Nonpregnant, nonbreastfeeding women. Women of child bearing potential must agree to use birth control during the first 150 days after treatment.
5. Healthy, as determined by a physician on the basis of a physical examination, ECG, and a thorough review of the medical history and clinical laboratory results
6. Adequate hematologic, renal, and hepatic function
7. Skin microfilarial density within the required range for the cohort

Exclusion Criteria:

1. Participation in any studies other than purely observational ones, within 4 weeks before test article administration.
2. Any vaccination within 4 weeks before test article administration
3. Acute infection requiring therapy within the last 10 days before test article administration
4. Administration of any medication (with the exception of medication required to treat any reactions during the screening fluorescein angiography (chlorpheniramine) or paracetamol) or herbal preparation within 10 days prior to test article administration or any condition currently requiring regular medication
5. Clinically significant ECG abnormalities or history of cardiac abnormality
6. Past or current history of neurological or neuropsychiatric disease or epilepsy
7. Subjects with orthostatic hypotension at the screening evaluation
8. History of drug or alcohol abuse or regular use of ≥ 3 cigarettes per day
9. Use of alcohol or other drugs of abuse within 72 hours before test article administration
10. Any condition, in the investigator's opinion, that places the subject at undue risk
11. Subjects who have donated blood within 8 weeks before study entry
12. Subjects with ocular onchocerciasis in cohorts intended to enroll subjects with mild infection. Ocular onchocerciasis is defined by the presence of live or dead microfilariae, onchocercal punctate opacities, onchocercal lesions of the posterior segment or lesions that mimic those seen in onchocerciasis.
13. Subjects with hyperreactive onchodermatitis
14. Antifilarial therapy within the previous 5 years
15. Coincidental infection with Loa Loa
16. Female subjects of childbearing potential with a contraindication to DMPA if not on Norplant
17. Any other condition which the investigator feels would exclude the subject from the study

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: 2 mg moxidectin; 2 mg moxidectin (Dose-escalation 1st step)	Drug: 2 mg moxidectin; Single-dose, tablet encapsulated for blinding
Active Comparator: Ivermectin 150 mcg/kg; Active comparator arm (ivermectin 150 mcg/kg).	Drug: ivermectin 150 mcg/kg; Single-dose, tablets encapsulated for blinding
Experimental: 4 mg moxidectin; 4 mg moxidectin (dose escalation second step)	Drug: 4 mg moxidectin; Single dose, tablets encapsulated for blinding
Experimental: 8 mg moxidectin; 8 mg moxidectin (dose escalation third step)	Drug: 8 mg moxidectin; single dose, tablets encapsulated for blinding

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of clinical adverse events and clinically significant laboratory test results	Duration of follow up (18 months)

Secondary Outcome Measures

Outcome Measure	Time Frame
Skin mf counts at day 8 and months 1, 2, 3, 6, 12 and 18	day 8 and months 1, 2, 3, 6, 12, 18
Nodulectomy at 18 months	18 months
Pharmacokinetics (PKs) at days 1, 2, 4, 13, and 18 and months 1, 2, 3, 6 and 12	days 1, 2, 4, 13, and 18 and months 1, 2, 3, 6 and 12

Collaborators and Investigators

• Sponsor: Medicines Development for Global Health
• Collaborators: World Health Organization
• Investigators: Principal Investigator: Nicholas Opoku, MD, Onchocerciasis Chemotherapy Research Center, Hohoe, Ghana

Publications and helpful links

General Publications

• Awadzi K, Opoku NO, Attah SK, Lazdins-Helds J, Kuesel AC. A randomized, single-ascending-dose, ivermectin-controlled, double-blind study of moxidectin in Onchocerca volvulus infection. PLoS Negl Trop Dis. 2014 Jun 26;8(6):e2953. doi: 10.1371/journal.pntd.0002953. eCollection 2014 Jun.

Helpful Links

• Awadzi et al 2014

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2006
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 29, 2009

Study Registration Dates

• First Submitted: March 7, 2006
• First Submitted That Met QC Criteria: March 7, 2006
• First Posted (Estimate): March 9, 2006

Study Record Updates

• Last Update Posted (Actual): December 15, 2022
• Last Update Submitted That Met QC Criteria: December 13, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: ivermectin; moxidectin; onchocerciasis; onchocerca volvulus; river blindness
• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Infections; Gastrointestinal Diseases; Intestinal Diseases; Pathological Conditions, Anatomical; Parasitic Diseases; Skin Diseases, Parasitic; Skin Diseases, Infectious; Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Intestinal Obstruction; Filariasis; Torsion Abnormality; Onchocerciasis; Intestinal Volvulus; Anti-Infective Agents; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Ivermectin; Moxidectin
• Other Study ID Numbers: 3110A1-200-GH; B1751004 (Other Identifier: Protocol ID: Pfizer); OCRC 33 (Other Identifier: Protocol ID: WHO, OCRC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No