A Study to Evaluate the Efficacy and Safety of Oral VT-1161 in Patients With Onychomycosis of the Toenail

Study Overview
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Brief Summary
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Several properties of VT-1161 suggest that it might be a safer and more effective treatment for onychomycosis of the toenail (also known as toenail fungus) than other oral antifungal medicines. This study will evaluate the effectiveness and safety of VT-1161 for the treatment of toenail onychomycosis and consists of a screening phase, a 24-week treatment phase in which the patient will take either active drug, placebo or a combination of the 2 (according to random assignment), an initial observational phase of 36 weeks and an additional observational study extension of 9 months. The additional 9-month observational study extension was added with a protocol amendment and patient participation was optional.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of VT-1161 Oral Tablets in the Treatment of Patients With Distal Lateral Subungual Onychomycosis of the Toenail

Conditions
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Onychomycosis

Intervention / Treatment
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* Drug: VT-1161
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Distal subungual onychomycosis of the great toenail, affecting at least ≥25 to ≤75% of nail. Positive culture for dermatophytes and positive KOH. Nail ≤ 3 mm thick at the distal end. At least ≥ 2 mm of the proximal end of the great toenail must be free of infection. Subjects must be able to swallow tablets. Women of childbearing potential and males must use acceptable birth control methods throughout the study. Key Exclusion Criteria: Presence of subungual hematoma or melanonychia. Presence of dermatophytoma/nail streaks and severe onychorrhexis. Significant dystrophy or anatomic abnormalities of the great toenail. Presence of any other infections of the foot. Evidence of clinically significant major organ disease. Poorly controlled diabetes mellitus. Onychomycosis involving more than 8 toe nails. Recent use of systemic antifungal therapy. Recent of any topical antifungal nail therapy. Recent use of systemic corticosteroid therapy. Recent use of immunosuppressive medication. History of prolonged QT intervals. Known human immunodeficiency virus (HIV) infection. Known significant renal or hepatic impairment. Known history of intolerance or hypersensitivity to azole antifungal drugs.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose 12-week<br>2 VT-1161 150mg tablets and 2 placebo tablets once daily for 2 weeks, then once weekly for 10 weeks, followed by 4 placebo tablets once weekly for 12 weeks | Drug: VT-1161<br> <br> |
| Experimental: Low dose 24-week<br>2 VT-1161 150mg tablets and 2 placebo tablets once daily for 2 weeks, then once weekly for 22 weeks | Drug: VT-1161<br> <br> |
| Experimental: High dose 12-week<br>4 VT-1161 150mg tablets once daily for 2 weeks, then once weekly for 10 weeks, followed by 4 placebo tablets once weekly for 12 weeks | Drug: VT-1161<br> <br> |
| Experimental: High dose 24-week<br>4 VT-1161 150mg tablets once daily for 2 weeks, then once weekly for 22 weeks | Drug: VT-1161<br> <br> |
| Placebo Comparator: Placebo<br>4 placebo tablets once daily for 2 weeks, then once weekly for 22 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Subjects in the Intent-to-treat Population With Complete Cure, Defined as Clinical AND Mycological Cure, at Week 48 | Complete cure was defined as 0% nail involvement and an Investigator Global Assessment (IGA) score of 0. Mycological cure was defined as negative potassium hydroxide (KOH) and negative dermatophyte culture. Investigator Global Assessment (IGA) scoring: 0: 0% nail involvement >0% to ≤10% nail involvement >10% to <25% nail involvement ≥25% to ≤50% nail involvement >50% to ≤75% nail involvement >75% nail involvement | 48 weeks | 
| Study Extension - Number of Subjects Who Experienced Treatment-emergent Adverse Events and Lab Abnormalities |  | 9 months |