To Evaluate Hallux Terbinafine Subungual Gel (HSG) in the Treatment of Onychomycosis

An Open Label Phase 2a Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Hallux Terbinafine Subungual Gel Administered to the Toenail Bed of Patients With Distal-Lateral Subungual Onychomycosis

The key objective is to establish the efficacy, safety, tolerability, and pharmacokinetics of investigational drug Hallux Terbinafine Subungual Gel (HSG) administered over 44 weeks to patients with distal-lateral subungual onychomycosis (DLSO).

Study Overview

• Status: Active, not recruiting
• Conditions: Onychomycosis of Toenail
• Intervention / Treatment: Drug: Hallux Terbinafine Subungual Gel

Detailed Description

Primary Efficacy: To identify patients achieving Complete Cure in the target toenail at Week 52.

Secondary Efficacy: To identify patients that have achieved 1) Clinical Cure, 2) Mycological Cure, and/or 3) Positive Response in the target toenail at Week 52.

Plasma Pharmacokinetics: To characterize concentrations of terbinafine and major metabolite in a subpopulation of patients over the study period.

Nail Pharmacokinetics: To characterize concentrations of terbinafine and major metabolite in distal nail clippings in patients over the study period.

HSG Safety and Tolerability Profile: To establish from plasma pharmacokinetics, related adverse events, treatment site reactions, pain, clinically significant changes in medical condition and/or medications, and clinically significant changes in liver function, serum chemistry, urinalysis, and complete blood count over the study period.

Subungual Topical Procedure: To establish the ease and durability of once monthly and once bi-monthly HSG subungual topical treatments, the Investigator will record at selected time points 1) nail measurements indicating progressive clearing, 2) the ease and depth of each topical administration, 3) the investigational drug volume administered each treatment, and 4) patient tolerability.

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mark Taylor; Phone Number: 949-637-4656; Email: mark@halluxinc.com

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • OrthoArizona - East Valley Foot & Ankle Specialists
  • Colorado
    • Parker, Colorado, United States, 80134
      • Front Range Foot and Ankle Clinic
  • Oregon
    • Portland, Oregon, United States, 97210
      • Oregon Dermatology & Research Center
  • Texas
    • College Station, Texas, United States, 77845
      • J&S Studies

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and females 18 - 75 years of age inclusive
• Patients with DLSO of at least one great toe
• Patients with DLSO in the target toe confirmed by positive KOH and positive fungal culture for dermatophytes
• Willingness to abstain from pedicures, nail clipping, or application of nail polish or nail cosmetics to their toenails over the study period

Exclusion Criteria:

• History of any significant chronic fungal disease other than onychomycosis or an immunocompromised condition
• Any previous surgery to or abnormalities of the target toe that in the investigator's opinion could prevent the toenail surface area from clearing even if eradication of the DLSO infection is achieved
• Participation in another clinical study of an investigational drug or device within 3 months of screening
• No administration of oral terbinafine or another oral antifungal within 6 months of screening
• No topical antifungal used for onychomycosis or a dermatophyte infection (i.e. tinea pedis) within 3 months of screening
• No uncontrolled diabetes mellitus
• No severe psoriasis or severe atopic dermatitis

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HSG; Hallux terbinafine subungual gel	Drug: Hallux Terbinafine Subungual Gel; Hallux Terbinafine Subungual Gel (HSG) administered every 1 to 2 months over 44 weeks.; Other Names: HSG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Cure at Week 52 in the Target Toe	Complete Cure is defined as 1) 100% healthy, clear nail, and 2) negative mycology. Healthy, clear nail is absent any disease involvement attributable to DLSO and is determined by Investigator Global Assessment (IGA). Negative mycology is defined as zero visualization of septate hyphae by KOH microscopy (negative KOH) combined with a fungal culture negative for causal dermatophytes (negative fungal culture).	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Cure in the Target Toe	100% healthy, clear nail	Week 52
Mycological Cure in the Target Toe	Negative KOH, negative fungal culture	Week 52
Positive Response in the Target Toe	≥ 80% decrease in disease involvement	Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Pharmacokinetics	To characterize plasma concentrations of terbinafine and metabolite from a subset of patients over the study period	Week 52
Nail Pharmacokinetics	To characterize nail concentrations of terbinafine and metabolite from patients over the study period	Week 52
Subungual Topical Procedure	To evaluate the ease and durability of once monthly and once bi-monthly HSG subungual topical treatments to the target toe over 44 weeks. Nail measurements indicating progressive clearing are recorded from an Investigator Global Assessment scale referencing % disease involvement corroborated by nail image analysis. The ease and durability of subungual topical treatment is established using a 5-point Likert Scale. Patient local tolerability is established using a Treatment Site Assessment Scale and Pain Intensity Scale.	Week 44
Patient Global Assessment	To establish each patient's impression of DLSO improvement in their target toe over the study period, patients will reference the following scale (0 = clear of DLSO, 1 = marked improvement of DLSO, 2 = moderately improved DLSO, 3 = slightly improved DLSO, 4 = unchanged, 5 = worse)	Week 52
Safety and Tolerability: Established from patient incidence of Treatment-Emergent Adverse Events	Indicated by the number of patients with treatment-related adverse events assessed by Common Terminology Criteria for Adverse Events (CTCAE)	Monitored from screening visit to end of study visit (Week 52)
Safety and Tolerability: Established from clinical laboratory results	Indicated by clinically significant changes in patient liver function, serum chemistry, urinalysis, and complete blood count over the study period	Monitored at selected time points from screening visit to end of study visit (Week 52)
Safety and Tolerability: Established from patient reported medical condition and use of medications	Monitored by assessing clinically significant changes in patient medical condition and/or use of medications over the study period	Monitored from screening visit to end of study visit (Week 52)

Collaborators and Investigators

• Sponsor: Hallux, Inc.
• Investigators: Principal Investigator: Phoebe Rich, MD, Oregon Dermatology and Research Center; Principal Investigator: Lewis H. Freed, DPM, OrthoArizona, East Valley Foot & Ankle Specialists; Principal Investigator: Terry M. Jones, MD, J&S Studies; Principal Investigator: Daniel P. Mallett, DPM, Front Range Foot and Ankle Clinic

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2022
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: October 28, 2021
• First Submitted That Met QC Criteria: November 16, 2021
• First Posted (Actual): November 26, 2021

Study Record Updates

• Last Update Posted (Actual): August 7, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Onychomycosis
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Mycoses; Tinea; Dermatomycoses; Nail Diseases; Onychomycosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antifungal Agents; Terbinafine
• Other Study ID Numbers: HSG-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is a phase II study. Individual participant data (IPD) of this study will not be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No