Efficacy and Safety Study of Moxidectin in Adults With Scabies

Study Overview
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Brief Summary
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Moxidectin is not approved to treat scabies in humans. The effective dose of moxidectin to treat scabies is not known. This study aims to assess the efficacy of a single administration of 8 mg, 16 mg, or 32 mg moxidectin per oral in achieving Scabies Complete Cure at Day 28. This study also aims to assess the safety of three strengths of single moxidectin doses in adults with scabies.

Official Title
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A Phase 2, Placebo-controlled, Double-blind, Randomized, Dose Ranging, Efficacy and Safety Study of Orally Administered Moxidectin in Adults With Scabies.

Conditions
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Scabies

Intervention / Treatment
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* Drug: Moxidectin Oral Product
* Drug: Moxidectin Oral Product
* Drug: Moxidectin Oral Product
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or older. Provided written informed consent. Diagnosis of active scabies infestation confirmed by the presence of clinical signs and symptoms (evidence of burrows or typical inflammatory/noninflammatory lesions and pruritus) and either microscopic confirmation of scabies mite(s), ova or scybala by skin scraping or dermoscopy. All female subjects of childbearing potential must agree to the use of a highly effective method of birth control until 16 weeks after administration of Investigational Product (IP). Exclusion Criteria: Diagnosis of crusted/Norwegian scabies or scabies presentation that, in the opinion of the Investigator, would require treatment with more than one standard of care treatment for scabies (e.g., scabies requiring concurrent topical and oral treatment). History of chronic or recurrent dermatologic disease or skin conditions other than scabies that could interfere with the diagnosis of scabies and evaluation of cure. Received any treatment with one or more scabicides within the 28 days prior to Screening, or between Screening and Baseline, including but not limited to permethrin, ivermectin, benzyl benzoate, sulfur, lindane, crotamiton, malathion, tea tree oil or spinosad. Body mass index > 35 kg/m2. Creatinine clearance < 30 mL/min (using Cockcroft-Gault equation). Both total bilirubin >1.5 x upper limit of normal (ULN) and AST > ULN. Abnormal and clinically relevant findings in hematology or biochemistry assessments at Screening, or in vital signs, 12-lead ECG, or physical examination at Screening and/or Baseline, that in the opinion of the Investigator would put the subjects at increased risk from participating in the study, confound study evaluations, or may interfere with study conduct. 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 in the opinion of the Investigator would put the subjects at increased risk from participating in the study, confound study evaluations, or interfere with the study conduct. Use of topical steroids, systemic or high-dose inhaled corticosteroids (>500 µg per day of fluticasone propionate or equivalent for adults), or other immunomodulators within 14 days of Baseline. Requiring ongoing treatment with, or received within 5 half-lives before Screening, any of the following medications that are clinical BCRP inhibitors: curcurmin (turmeric) supplements, cyclosporine A, darolutamide, eltrombopag, febuxostat, fostamatinib, rolapitant and teriflunomide. Received an investigational agent within 28 days of Screening (or 5 half-lives of the investigational agent, whichever is longer). Known or suspected hypersensitivity to macrocyclic lactones or excipients used in the formulation of moxidectin or ivermectin. Known or suspected hypersensitivity to any of the components in permethrin 5% cream, to any synthetic pyrethroid or pyrethrin, or to the components of spinosad 0.9% topical suspension. Known, suspected or at risk of Loa loa coinfection. Difficulty swallowing tablets or capsules. Pregnant or breastfeeding or planning to become pregnant from Screening until 16 weeks after treatment with IP. Known or suspected alcohol or illicit substance abuse. Unwilling, unlikely or unable to comply with all protocol specified assessments. Previous enrolment in this study. Previous moxidectin exposure within 6 months (5 half-lives) from Baseline. Has household members who refuse or are unable to receive permethrin 5% cream treatment for scabies.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Placebo-controlled, double-blind, randomized, dose ranging study. Four cohorts of 50 subjects per cohort are planned. Subjects will be randomized 1:1:1:1 to receive Moxidectin 8mg, Moxidectin 16mg, Moxidectin 32mg or Placebo as a single oral dose.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Moxidectin 8mg<br>Moxidectin 8 mg (over encapsulated) will be administered as a single dose on Day 0. Each subject will receive the same number of capsules made up of moxidectin 2 mg over encapsulated tablets and placebo capsules to maintain the blind. | Drug: Moxidectin Oral Product<br>* The required number of moxidectin 2 mg tablet over encapsulated capsules will be administered as a single dose with placebo capsules to match as required<br>|
| Experimental: Moxidectin 16mg<br>Moxidectin 16 mg (over encapsulated) will be administered as a single dose on Day 0. Each subject will receive the same number of capsules made up of moxidectin 2 mg over encapsulated tablets and placebo capsules to maintain the blind. | Drug: Moxidectin Oral Product<br>* The required number of moxidectin 2 mg tablet over encapsulated capsules will be administered as a single dose with placebo capsules to match as required<br>|
| Experimental: Moxidectin 32mg<br>Moxidectin 32 mg (over encapsulated) will be administered as a single dose on Day 0. | Drug: Moxidectin Oral Product<br>* The required number of moxidectin 2 mg tablet over encapsulated capsules will be administered as a single dose.<br>|
| Placebo Comparator: Placebo<br>16 Placebo capsules will be administered as a single dose on Day 0. | Drug: Placebo<br>* 16 placebo capsules will be administered as a single dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of index subjects achieving complete cure (Efficacy) | Proportion of index subjects achieving Complete Cure at Day 28. Complete Cure is defined as demonstration of both: Clinical cure: all signs of scabies have completely resolved, including burrows, inflammatory/noninflammatory lesions and pruritus. And Microscopic or dermatoscopic cure demonstrating the absence of scabies mites, eggs, and/or scybala, and negative dermoscopy for burrows. | 28 Days | 
| Incidence and severity of Treatment Emergent Adverse Event (Safety) | Incidence and severity of Treatment Emergent Adverse Event (TEAEs), Incidence of serious TEAEs and Incidence of TEAEs leading to study withdrawal and/or death. | 84 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Moxidectin, Oral