Dose-finding Study of Moxidectin for Treatment of Scabies

A Phase II, Randomized, Double-blind, Parallel Group Dose Finding Study of Single Oral Doses of Moxidectin in Adults With Scabies

The effective dose of moxidectin to treat human scabies is not known. This study aims to provide proof of concept that a single dose of moxidectin is effective in eliminating the scabies parasite in humans and to enable the determination of an optimal dose of moxidectin for treatment of scabies for further clinical studies.

Study Overview

• Status: Completed
• Conditions: Scabies
• Intervention / Treatment: Drug: Moxidectin Oral Product

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Darwin, Australia
    • Royal Darwin Hospital
• Austria
  • Vienna, Austria
    • Medizinischen Universität Wien
• France
  • Créteil, France
    • Hôpital Henri Mondor AP-HP
  • Nice, France
    • Chu Nice Hopital Archet 2
  • Saint-Priest-en-Jarez, France
    • CHU SAINT-ETIENNE Hôpital Nord

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged ≥ 18 years.
2. Provision of written informed consent.
3. Parasitologically confirmed active Sarcoptes scabiei infestation, defined as the presence of at least two lesions (which may include burrows), each containing at least one live (internal and/or external structures discernable) adult Sarcoptes scabiei mite observed by reflectance confocal microscopy.
4. Agree to the use of reliable contraceptive measures if female or male partner of a female of child-bearing potential from Screening and until 6 months after treatment with study product.

Exclusion Criteria:

1. History of chronic or recurring dermatologic disease (other than scabies) that could interfere with the diagnosis and/or subsequent clinical assessment of scabies.
2. Diagnosis of crusted/Norwegian scabies or scabies that, in the opinion of the Investigator, would require treatment with more than one standard of care (e.g. scabies requiring concurrent topical and oral treatment).
3. Received any treatment for scabies within 7 days of Screening, including but not limited to permethrin, ivermectin, benzyl benzoate, lindane, crotamiton, malathion, and/or tea tree oil.
4. Presence of any other clinically relevant condition, including infection, immunological disorder, malignant disease, and/or other underlying condition or circumstance at Screening or Baseline that would put the subject at increased risk from participating in the study or confound study evaluations.
5. Poor venous access.
6. Received an investigational agent within 28 days of Screening (or 5 half-lives of the investigational agent, whichever is longer).
7. Body Mass Index over 35 kg/m2.
8. Clinically relevant abnormal findings in vital signs, 12-lead electrocardiogram (ECG), or physical examination at Screening and/or Baseline in the opinion of the Investigator.

9. Clinically relevant laboratory abnormalities at Screening, including:

   1. alanine aminotransferase or aspartate aminotransferase > 2.5 x upper limit of reference range;
   2. creatinine > 2.0 milligrams per deciliter (mg/dL);
   3. hemoglobin < 9.5 g/dL (female) or <10.5 g/dL (male);
   4. amylase > 2.0 x upper limit of reference range.
10. Known or suspected hypersensitivity to macrocyclic lactones or excipients used in the formulation of moxidectin.
11. Use of systemic steroids within 14 days of Screening, or history of prolonged use of systemic and/or high-dose inhaled corticosteroids, or use of topical steroids for 7 out of the 14 days prior to Screening.
12. Subjects with known or suspected Loa loa coinfection.
13. Difficulty swallowing tablets.
14. Pregnant or breastfeeding, or planning to become pregnant.
15. Known or suspected alcohol or illicit substance abuse.
16. Unwilling, unlikely or unable to comply with all protocol specified assessments.
17. Previous enrolment and treatment with moxidectin in this 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: Moxidectin 2 mg; Moxidectin 2 mg will be administered as a single dose. Each subject will receive the same number of tablets made up of moxidectin 2 mg tablets and placebo tablets to maintain the blind.	Drug: Moxidectin Oral Product; The required number of moxidectin 2 mg oral tablets will be administered as a single dose with placebo to match as required
Experimental: Moxidectin 8 mg; Moxidectin 8 mg will be administered as a single dose. Each subject will receive the same number of tablets made up of moxidectin 2 mg tablets and placebo tablets to maintain the blind.	Drug: Moxidectin Oral Product; The required number of moxidectin 2 mg oral tablets will be administered as a single dose with placebo to match as required
Experimental: Moxidectin 20 mg; Moxidectin 20 mg will be administered as a single dose. Each subject will receive the same number of tablets made up of moxidectin 2 mg tablets and placebo tablets to maintain the blind.	Drug: Moxidectin Oral Product; The required number of moxidectin 2 mg oral tablets will be administered as a single dose with placebo to match as required
Experimental: Moxidectin 36 mg; Moxidectin 36 mg will be administered as a single dose. Each subject will receive the same number of tablets made up of moxidectin 2 mg tablets and placebo tablets to maintain the blind.	Drug: Moxidectin Oral Product; The required number of moxidectin 2 mg oral tablets will be administered as a single dose with placebo to match as required

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality Rate for Adult Scabies Mites	Adult scabies mite death was based on the reflectance confocal microscopy (RCM) morphology assessment of 2 live adult scabies mites nominated pre-treatment (Baseline), hence overall number of units analyzed are different from the overall number of participants. For the outcome measure, the number of adult mites assessed at each timepoint is the sum of the number of adult mites from all participants in the analysis population for each dose. Therefore, mortality was assessed in 2 mites in the 2 mg group, 6 in the 8 mg group, 8 in the 20 mg group and 14 in the 32 mg group. Adult mite death was defined as the degradation (homogenization of internal structures and/or external anatomic structures, and increased reflectance) of the adult mite observed by RCM. The number of dead mites was assessed at Hours 4, 8, 24, 48 and 72, and Days 7, 14 and 28 compared to the baseline adult mites.	28 days
Summary of Participants With Most Commonly Occurring Adverse Events by Preferred Term (Safety Analysis Set)	No formal statistical analysis of AEs was undertaken. Adverse events reported in this Section refer to treatment emergent adverse events (TEAE), defined as AEs that started, or worsened, on or after the start of the administration of Investigational Product (Moxidectin). Moxidectin was generally well tolerated, with no treatment-related SAEs reported and no treatment emergent adverse event (TEAEs) leading to study withdrawal or resulting in death. Treatment-Emergent Adverse Events by MedDRA System Organ Class and Preferred Term. Data up to and including the Day 28 assessment for each subject.	Day 0 to Day 28 inclusive
Number of Participants and Severity of Adverse Events	Number of participants with Adverse events reported in this Section refer to treatment emergent adverse events (TEAE), defined as AEs that started, or worsened, on or after the start of the administration of IP. Data up to and including the Day 28 assessment for each subject. The severity of adverse events were assessed using the Toxicity Grading Scale for Healthy Adult and Adolescent volunteers Enrolled in Preventive Vaccine Clinical Trials.	Day 0 to Day 28 inclusive

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of Moxidectin Plasma Concentrations	The final PK analysis dataset included a total of 240 evaluable PK samples from 22 subjects. All pre-dose samples were below the limit of quantitation (BQL).	Nominal time of PK sample collection was Pre-dose, 2hours (h), 3h, 4h, 8h, Day 1 (24h), Day 2 (48h), Day 3 (72h), Day 7 (168h), Day 14 (336h) and Day 28 (672h)
Analysis of Moxidectin Maximum Plasma Concentrations (Cmax)	The final PK analysis dataset included a total of 240 evaluable PK samples from 22 subjects. All pre-dose samples were below the limit of quantitation (BQL).	Nominal time of PK sample collection was Pre-dose, 2hours (h), 3h, 4h, 8h, Day 1 (24h), Day 2 (48h), Day 3 (72h), Day 7 (168h), Day 14 (336h) and Day 28 (672h)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Scabies Signs and Symptoms	The incidence and severity of signs and symptoms of scabies infection will be explored using a clinician-reported scabies severity assessment.	28 days
Severity of Pruritus	The severity of pruritus will be determined using the Numerical Rating Scale where 0="no itch" and 10="worst itch imaginable"	28 days

Collaborators and Investigators

• Sponsor: Medicines Development for Global Health

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2020
• Primary Completion (Actual): February 28, 2022
• Study Completion (Actual): February 28, 2022

Study Registration Dates

• First Submitted: March 18, 2019
• First Submitted That Met QC Criteria: April 3, 2019
• First Posted (Actual): April 5, 2019

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: oral; moxidectin; acaricide
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Parasitic Diseases; Ectoparasitic Infestations; Skin Diseases, Parasitic; Skin Diseases, Infectious; Mite Infestations; Scabies; Anti-Infective Agents; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Moxidectin
• Other Study ID Numbers: MDGH-MOX-2001

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