A Study of ATB1651 in Adults With Mild to Moderate Onychomycosis

A Phase 1, First in Human, Randomized, Double-Blind, Placebo-Controlled Multiple Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of ATB1651 in Adults With Mild to Moderate Onychomycosis

The study is designed to evaluate the Safety, Tolerability and Pharmacokinetics of ATB1651 in participants with mild to moderate onychomycosis.

Study Overview

• Status: Completed
• Conditions: Onychomycosis
• Intervention / Treatment: Drug: ATB1651, 2 mg/mL; Drug: ATB1651, 5 mg/mL; Drug: ATB1651, 10 mg/mL; Drug: ATB1651, 20 mg/mL; Drug: ATB1651, 30 mg/mL; Other: Placebo

Detailed Description

Onychomycosis (also known as tinea unguium) is a contagious infection of toe nails by fungal organisms including dermatophytes, yeast, and molds.

This is phase 1, first in human, randomized, double-blind, placebo-controlled, MAD study designed to assess the safety, tolerability, and PK of ATB1651 when administered in participants with mild to moderate onychomycosis.

The study consists of 2 parts. In both parts, participants will receive multiple doses of ATB1651 applied to 1 affected great toenail and the remaining toenails (affected or not)

Part A: Participants will be enrolled into 1 of 3 cohorts and randomized to receive either ATB1651 or placebo at a ratio of 2:1.

Up to 2 additional cohorts may be added at the discretion of the Sponsor and Safety Monitoring Committee, if deemed necessary

Part B: Participants will be randomized within a single cohort to receive either ATB1651 or placebo at a ratio of 4:1

There will be 18 participants enrolled in part A, 30 participants in part B

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Christchurch, New Zealand, 8011
    • New Zealand Clinical Research Christchurch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Confirmation of onychomycosis by mycological staining and/or culture from affected great toenail(s).
2. Appearance of onychomycosis involving 20% to 70% of 1 (or both) affected great toenail(s) as determined by visual inspection after the nail has been trimmed. If the percentage of infection is outside this range but is still considered appropriate for this study, based on the overall impression of the Investigator, participation can be considered in consultation with the Medical Monitor.
3. The combined thickness of the distal nail plate at the associated hyperkeratotic nail bed is less than 3 mm.
4. Medically healthy with clinically insignificant Screening results (eg, laboratory profiles, medical history, ECGs, physical exam), as judged by the PI.
5. Negative urine drug screen and alcohol breath test at Screening and Day 1.
6. Body Mass Index (BMI) between 17.5 and 35.0, inclusive.
7. Agree to adhere to the current state and national advice regarding minimizing exposure to coronavirus disease of 2019 (COVID-19) from the Screening visit until the EOS visit.

Exclusion Criteria:

1. History of allergy to any of the excipients in ATB1651.
2. Positive COVID-19 test at Screening or any symptoms consistent with COVID-19 prior to initial dosing.
3. Positive test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV) antibody at Screening.
4. Have any underlying physical or psychological medical conditions that, in the opinion of the Investigator, would make it unlikely that the participant will comply with the study.
5. Pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study, including the follow-up period.
6. Unwilling to refrain from the use of nail cosmetics such as clear and/ or colored nail lacquers from the Screening visit until the end of the study.
7. Use of any IP or investigational medical device within 30 days prior to Screening, or 5 half-lives of the product (whichever is the longest) or participation in more than 4 investigational drug studies within 1 year prior to Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A (ATB1651, 2 mg/mL); The planned ATB1651 dose level of 2 mg/mL. Six participants are expected to be enrolled in each arm.	Drug: ATB1651, 2 mg/mL; The participants will apply daily doses of ATB1651, 2 mg/mL to all 10 toenails including at least 1 affected great toenail for 28 days
Experimental: B (ATB1651, 5 mg/mL); The planned ATB1651 dose level of 5 mg/mL. Six participants are expected to be enrolled in each arm.	Drug: ATB1651, 5 mg/mL; The participants will apply daily doses of ATB1651, 5 mg/mL to all 10 toenails including at least 1 affected great toenail for 28 days
Experimental: C (ATB1651, 10 mg/mL); The planned ATB1651 dose level of 10 mg/mL. Six participants are expected to be enrolled in each arm.	Drug: ATB1651, 10 mg/mL; The participants will apply daily doses of ATB1651, 10 mg/mL to all 10 toenails including at least 1 affected great toenail for 28 days
Experimental: D (ATB1651, 20 mg/mL); The planned ATB1651 dose level of 20 mg/mL. Six participants are expected to be enrolled in each arm.	Drug: ATB1651, 20 mg/mL; The participants will apply daily doses of ATB1651, 20 mg/mL to all 10 toenails including at least 1 affected great toenail for 28 days
Placebo Comparator: E (ATB1651, 30 mg/mL); The planned ATB1651 dose level of 30 mg/mL. Six participants are expected to be enrolled in each arm.	Drug: ATB1651, 30 mg/mL; The participants will apply daily doses of ATB1651, 30 mg/mL to all 10 toenails including at least 1 affected great toenail for 28 days
Placebo Comparator: F (placebo); The participants will apply placebo for 28 days. Six participants are expected to be enrolled in each arm.	Other: Placebo; The participants will apply placebo to all 10 toenails including at least 1 affected great toenail for 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the safety and tolerability of multiple ascending doses (MAD) of ATB1651 in participants with mild to moderate onychomycosis through the percentage and severity of adverse events including pain, erythema and local irritation	Adverse Events will be coded using the most current version of Medical Dictionary for Regulatory Activities (MedDRA®) Version 22.0 or higher	From baseline to end of study treatment up to 56 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the efficacy of ATB1651 in improving signs and symptoms of onychomycosis in participants with mild to moderate onychomycosis	Efficacy of ATB1651 assessed based on Mycological evaluation of the affected great toenail(s) where ATB1651 was applied	From baseline to end of study treatment up to 56 days
To assess the efficacy of ATB1651 in improving signs and symptoms of onychomycosis in participants with mild to moderate onychomycosis	Difference in the appearance of the affected great toenail(s) as determined by photographs throughout treatment and follow-up periods	From baseline to end of study treatment up to 56 days
To assess whether there is systemic exposure following multiple doses of ATB1651 through pharmacokinetic analysis Parameters: Maximum plasma concentration and Time to maximum plasma concentration		From baseline to end of study treatment up to 56 days
To assess whether there is systemic exposure following multiple doses of ATB1651 through pharmacokinetic analysis Parameters: Apparent terminal elimination rate constant		From baseline to end of study treatment up to 56 days
To assess whether there is systemic exposure following multiple doses of ATB1651 through pharmacokinetic analysis Parameters: Area under the drug concentration-time curve, from time zero to 24 hours post dose		From baseline to end of study treatment up to 56 days
To assess whether there is systemic exposure following multiple doses of ATB1651 through pharmacokinetic analysis Parameters: Area under the drug concentration-time curve, from time zero to the last measurable concentration		From baseline to end of study treatment up to 56 days
To assess whether there is systemic exposure following multiple doses of ATB1651 through pharmacokinetic analysis Parameters: Area under the drug concentration-time curve, from time zero to infinity		From baseline to end of study treatment up to 56 days
To assess whether there is systemic exposure following multiple doses of ATB1651 through pharmacokinetic analysis Parameters: Apparent terminal half-life		From baseline to end of study treatment up to 56 days
To assess whether there is systemic exposure following multiple doses of ATB1651 through pharmacokinetic analysis Parameters: Apparent clearance		From baseline to end of study treatment up to 56 days
To assess whether there is systemic exposure following multiple doses of ATB1651 through pharmacokinetic analysis Parameters: Apparent terminal volume of distribution		From baseline to end of study treatment up to 56 days
To assess whether there is systemic exposure following multiple doses of ATB1651 through pharmacokinetic analysis Parameters: Plasma ATB1651 trough concentrations (Ctrough) during multiple dosing		From baseline to end of study treatment up to 56 days

Collaborators and Investigators

• Sponsor: AmtixBio Co., Ltd.
• Collaborators: Novotech (Australia) Pty Limited

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2022
• Primary Completion (Actual): June 3, 2023
• Study Completion (Actual): September 20, 2023

Study Registration Dates

• First Submitted: October 12, 2021
• First Submitted That Met QC Criteria: October 12, 2021
• First Posted (Actual): October 22, 2021

Study Record Updates

• Last Update Posted (Actual): October 11, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Infections; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Mycoses; Tinea; Dermatomycoses; Nail Diseases; Onychomycosis
• Other Study ID Numbers: ATB1651-101

Drug and device information, study documents

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