Dose-finding Study of Moxidectin for Treatment of Scabies

NCT03905265 | Completed Phase 2 Results FDA Drug

• 1 other identifier: MDGH-MOX-2001
• Study Type: interventional
• Target: 22
• Locations: 2 countries
• Sites: 4

Brief Summary

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.

Conditions

Scabies

Keywords

moxidectin; acaricide; oral

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Analysis of Moxidectin Plasma Concentrations

  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)

  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 Outcomes (2)

• Incidence and Severity of Scabies Signs and Symptoms

  28 days

• Severity of Pruritus

  28 days

Study Arms (4)

Moxidectin 2 mg

EXPERIMENTAL

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

Moxidectin 8 mg

EXPERIMENTAL

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

Moxidectin 20 mg

EXPERIMENTAL

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

Moxidectin 36 mg

EXPERIMENTAL

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

Interventions

Moxidectin Oral Product DRUG

The required number of moxidectin 2 mg oral tablets will be administered as a single dose with placebo to match as required

Moxidectin 2 mg; Moxidectin 20 mg; Moxidectin 36 mg; Moxidectin 8 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥ 18 years.
• Provision of written informed consent.
• 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.
• 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.

You may not qualify if:

• History of chronic or recurring dermatologic disease (other than scabies) that could interfere with the diagnosis and/or subsequent clinical assessment of scabies.
• 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).
• 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.
• 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.
• Poor venous access.
• Received an investigational agent within 28 days of Screening (or 5 half-lives of the investigational agent, whichever is longer).
• Body Mass Index over 35 kg/m2.
• 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.
• Clinically relevant laboratory abnormalities at Screening, including:
• alanine aminotransferase or aspartate aminotransferase \> 2.5 x upper limit of reference range;
• creatinine \> 2.0 milligrams per deciliter (mg/dL);
• hemoglobin \< 9.5 g/dL (female) or \<10.5 g/dL (male);
• amylase \> 2.0 x upper limit of reference range.
• Known or suspected hypersensitivity to macrocyclic lactones or excipients used in the formulation of moxidectin.
• 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.

Sponsors & Collaborators

• Medicines Development for Global Health: lead

Study Sites (5)

Royal Darwin Hospital

Darwin, Australia

Location

Medizinischen Universität Wien

Vienna, Austria

Location

Hopital Henri Mondor AP-HP

Créteil, France

Location

CHU Nice Hopital Archet 2

Nice, France

Location

CHU Saint-Etienne Hopital Nord

Saint-Priest-en-Jarez, France

Location

MeSH Terms

Conditions

Scabies

Condition Hierarchy (Ancestors)

Mite Infestations; Ectoparasitic Infestations; Skin Diseases, Parasitic; Parasitic Diseases; Infections; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

Small number of subjects, especially in the per-protocol analysis set, confounds interpretation of some study results.

Results Point of Contact

• Title: Clinical Project Manager
• Organization: Medicines Development for Global Health Limited

MDGH-MOX-2001@medicinesdevelopment.com

+61 399122400

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: To maintain blinding to treatment allocation, all subjects will receive treatment with the same number of tablets, comprised of moxidectin 2 mg tablets and matched placebo (as required).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel, double blind, multicenter, randomized, pharmacokinetic/pharmacodynamic study. Three cohorts of six subjects per cohort are planned. Subjects will be randomized 1:1:1 to receive 2, 8 or 20 mg moxidectin as a single oral dose. An additional cohort of 36 mg may be initiated with a target sample size of 6 subjects.

Study Record Dates

• First Submitted: March 18, 2019
• First Posted: April 5, 2019
• Study Start: January 13, 2020
• Primary Completion: February 28, 2022
• Study Completion: February 28, 2022
• Last Updated: September 22, 2023
• Results First Posted: September 22, 2023

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); FR (3)