A Study of ATB1651 in Adults With Mild to Moderate Onchomycosis

Official title

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the

Overview

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

Detailed description

This Phase 2, multicenter, randomized, double-blind, placebo-controlled study is designed to assess the efficacy, safety, and tolerability of ATB1651 when administered topically to the great (hallux) toenail of participants with mild to moderate onychomycosis who are otherwise healthy.

This study will enroll upto 120 participants in 3+1 (optional) sequential cohorts.

* Participants in Cohorts 1 to 3 will be randomized within each cohort to receive either ATB1651 3% or placebo at a ratio of 5:1. * An optional cohort (Cohort 4) may enroll up to 30 participants who will be randomized to receive either ATB1651 5% or placebo at a ratio of 5:1.

Dosing will start with Cohort 1 followed at least 4 weeks later by Cohort 2. The decision to continue dosing in Cohort 2 beyond 12 weeks and/or to commence Cohort 3, at the planned dosage regimen or a modified dosage regimen, will be determined by the Safety Review Committee (SRC).

Interventions

• Drug ATB1651-102- Cohort 1
  Dosage form- Topical solution; Dosage- 3% formulation The participants will apply the daily dose of 3% ATB1651 once daily to the affected great toenail for 12 weeks with a follow-up for 24 weeks.
• Drug ATB1651-102- Cohort 2
  Dosage form- Topical solution; Dosage- 3% formulation The participants will apply the daily dose of 3% ATB1651 once daily to the affected great toenail for 20 weeks with a follow-up for 16 weeks.
• Drug ATB1651-102- Cohort 3
  Dosage form- Topical solution; Dosage- 3% formulation The participants will apply the daily dose of 3% ATB1651 twice daily to the affected great toenail for 12 weeks with a follow-up for 24 weeks.
• Drug ATB1651-102- Cohort 4
  Dosage form- Topical solution; Dosage- 5% formulation The participants will apply the daily dose of 5% ATB1651 once daily to the affected great toenail for 12 weeks with a follow-up for 24 weeks.
• Drug Placebo
  participants will receive matching placebo across cohorts 1-4 of the study.

Primary outcome measures

• To evaluate the complete cure rate with topical ATB1651 3% and ATB1651 5% in participants with mild to moderate onychomycosis. [Time frame: From screening to end of study treatment up to 252 days]

Secondary outcome measures (10)

• To further evaluate the efficacy of topical ATB1651 3% and topical ATB1651 5% in participants with mild to moderate onychomycosis. [Time frame: From screening to end of study treatment up to 252 days]
• To assess and collect the percentage and severity of adverse events (AEs). [Time frame: From screening to end of study treatment up to 252 days]
• Maximum plasma concentration (Cmax) [Time frame: Cohort 1, 3 and 4- On day1, day 14, day 28, day 42, Day 56, day 70 and day 84; Cohort 2- Same as cohort 1+day 98, 112, day 126 and day 140]
• Time to maximum plasma concentration (Tmax) [Time frame: Cohort 1, 3 and 4- On day1, day 14, day 28, day 42, Day 56, day 70 and day 84; Cohort 2- Same as cohort 1+day 98, 112, day 126 and day 140]
• Apparent terminal elimination rate constant (λz) [Time frame: Cohort 1, 3 and 4- On day1, day 14, day 28, day 42, Day 56, day 70 and day 84; Cohort 2- Same as cohort 1+day 98, 112, day 126 and day 140]
• Area under curve (AUC) [Time frame: Cohort 1, 3 and 4- On day1, day 14, day 28, day 42, Day 56, day 70 and day 84; Cohort 2- Same as cohort 1+day 98, 112, day 126 and day 140]
• Apparent terminal half-life (t 1/2) [Time frame: Cohort 1, 3 and 5- On day1, day 14, day 28, day 42, Day 56, day 70 and day 84; Cohort 2- Same as cohort 1+day 98, 112, day 126 and day 140]
• Apparent clearance (CL) [Time frame: Cohort 1, 3 and 4- On day1, day 14, day 28, day 42, Day 56, day 70 and day 84; Cohort 2- Same as cohort 1+day 98, 112, day 126 and day 140]
• Apparent terminal volume of distribution (VD) [Time frame: Cohort 1, 3 and 4- On day1, day 14, day 28, day 42, Day 56, day 70 and day 84; Cohort 2- Same as cohort 1+day 98, 112, day 126 and day 140]
• Plasma ATB1651 trough concentrations (Ctrough) [Time frame: Cohort 1, 3 and 4- On day1, day 14, day 28, day 42, Day 56, day 70 and day 84; Cohort 2- Same as cohort 1+day 98, 112, day 126 and day 140]

Eligibility criteria

Inclusion criteria

• Confirmation of onychomycosis by positive mycological (KOH) staining and positive culture from affected great toenail(s).
• Appearance of onychomycosis involving 20% to 60% 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 Principal Investigator (PI), participation can be considered in consultation with the Medical Monitor (MM). The visual inspection results of the appearance of onychomycosis involving 20% to 60% of 1 (or both) affected great toenail(s) will be reviewed by the Sponsor before enrollment.
• The combined thickness of the distal nail plate at the associated hyperkeratotic nail bed is < 2 mm.
• Adult males and females, 18 to 70 years of age (inclusive) at the time of Screening.
• In good general health, with no significant medical history, and no clinically significant abnormalities on physical examination or ECG at Screening and/or before the first administration of IP at the discretion of the PI or designee. Participants with mild stable disease may be considered eligible at the discretion of the PI or designee.
• Body mass index (BMI) between 17.5 and 35.0 kg/m2, inclusive, at Screening.

Exclusion criteria

• History of allergy to any of the excipients in ATB1651.
• Positive test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV) antibody at Screening or Day 1.
• Underlying physical or psychological medical conditions that, in the opinion of the PI, would make it unlikely for the participant to comply with the protocol or complete the study per protocol.
• 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.
• 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.
• Diabetes mellitus requiring treatment other than diet and exercise.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

New Zealand · 1 center

• New Zealand Clinical Research Christchurch — Christchurch

Identifiers

NCT: NCT06327295 · ATB1651-102

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗