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Trial registered on ANZCTR

Registration number

ACTRN12620000697987

Ethics application status

Approved

Date submitted

29/04/2020

Date registered

23/06/2020

Date last updated

11/08/2022

Date data sharing statement initially provided

23/06/2020

Date results information initially provided

11/08/2022

Type of registration

Prospectively registered

Titles & IDs

Public title

Evaluation of HXP124 in the treatment of a fungal nail infection, onychomycosis.

Scientific title

A Phase II, Randomized, Double-blind, Vehicle-controlled Study to Investigate the Efficacy, Safety, and Tolerability of HXP124 in Patients with Mild to Moderate Onychomycosis.

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1255-3850

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Toenail Onychomycosis

Condition category

Condition code

Infection

Other infectious diseases

Skin

Dermatological conditions

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

In Cohort 1, participants with mild to moderate onychomycosis (n = 44) will be randomized to receive either active drug (20 mg/mL HXP124; n = 33) or vehicle (n = 11).
Cohort 1: 2 x 6 week once daily treatment with HXP124 or 2 x 6 week once daily treatment with placebo( N= 44, Active = 33 Placebo =11) Each treatment period will be separated by a 1-week washout period. Treatment periods end in a 27-week treatment-free follow up period. Administration is self-application of a topical solution to occur after showering and drying the effected toes.

In Cohort 2, participants with mild to moderate onychomycosis (n = 44) will be randomized to receive either active drug (20 mg/mL HXP124; n = 33) or vehicle (n = 11).
Cohort 2: 2 x 6 week once daily treatment separated by a 1-week washout period plus 1 x 23 week once weekly treatment with HXP124, or 2 x 6 week once daily treatment separated by a 1-week washout period plus 1 x 23 week once weekly treatment with placebo (N = 44, Active = 33, Placebo =11). Treatment periods end in a 4-week treatment-free follow up period. Administration is self-application of a topical solution to occur after showering and drying the effected toes.

In Cohort 3, participants with mild to moderate onychomycosis (n = 44) will be randomized to receive either active drug (20 mg/mL HXP124; n = 33) or vehicle (n = 11).
Cohort 3: 5 x 6 week once-daily treatment followed by 1 x 1 week once-daily treatment with HXP124,or 5 x 6 week once-daily treatment followed by 1 x 1 week once-daily treatment with placebo ( N= 44, Active = 33 Placebo =11).Each treatment period will be separated by a 1-week washout period. Treatment periods end in a 4-week treatment-free follow up period. Administration is self-application of a topical solution to occur after showering and drying the effected toes.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

The vehicle will be the excipients in a topical solution in the same bottle without the active (HXP124).

Control group

Placebo

Outcomes

Primary outcome [1]

To evaluate the safety and tolerability of 20 mg/mL topical HXP124 in treated participants with mild to moderate DLSO of the target great toenail.
Safety and Tolerability will be assessed by:
1. Incidence, nature, and severity of AEs and SAEs.
2. Incidence of treatment discontinuations due to AEs.
3. Changes in clinical laboratory tests from baseline over time; incidence of treatment emergent abnormal laboratory tests.
4. Physical examination abnormalities including incidence of application site reactions (burning/stinging, induration/edema, oozing/crusting, pruritis, erythema, pain and local irritation).
5. Changes in vital signs (systolic and diastolic blood pressures, respiratory rate, heart rate and body temperature) and 12-lead ECGs.

Timepoint [1]

Outcomes will be assessed at weeks 13, 24, 36 and 40 for all cohorts.

Secondary outcome [1]

These are composite secondary outcomes.

To evaluate the efficacy of 20 mg/mL topical HXP124 in treated participants with mild to moderate DLSO of the target great toenail.
Efficacy will be assessed by:
1. Percentage of participants in each treatment group (all cohorts) who at Week 13, Week 24, Week 36 and Week 40 following application of 20 mg/mL topical HXP124 achieve:
• Mycological Cure (negative microscopy stain and a negative fungal culture of the target toenail).The outcome will be assessed via mycological assessment
• Complete or Almost Complete Cure (defined as is less than or equal to 5% but greater than or equal to 0% infection of the target great toenail, in addition to both Mycological Cure parameters, i.e. negative microscopy stain (KOH) examination and a negative fungal culture of the target toenail).The outcome will be assessed via mycological assessment and digital measurement of the area of toenail infection.
• Clinical Efficacy (defined as 0% to less than or equal to 10% area of infection of the target great toenail).The outcome will be assessed via digital measurement of the area of toenail infection.
• Complete Cure (defined as 100% clear nail surface area of the target toenail, in addition to both a negative microscopy stain result and a negative fungal culture result of the target toenail).The outcome will be assessed via mycological assessment and digital measurement of the area of toenail infection.
• A change in clear nail surface area of greater than or equal to 20% from baseline. The outcome will be assessed via digital measurement of the area of toenail infection.

Timepoint [1]

Outcomes will be assessed at weeks 13, 24, 36 and 40 for all cohorts.

Secondary outcome [2]

These are composite secondary outcomes.
To determine if additional application of once weekly topical HXP124 (20 mg/mL) for 23 weeks (161 days), followed by a treatment free follow-up period of 4 weeks (28 days) affects rates of Mycological Cure, Complete or Almost Complete Cure and Clinical Efficacy in participants with mild to moderate DLSO of the target great toenail.
1. Percentage of participants in cohort 2 who at Week 13, Week 24, Week 36 and Week 40 following application of 20 mg/mL topical HXP124 achieve:
• Mycological Cure (negative microscopy stain and a negative fungal culture of the target toenail).The outcome will be assessed via mycological assessment.
• Complete or Almost Complete Cure (defined as is less than or equal to 5% but greater than or equal to 0% infection of the target great toenail, in addition to both Mycological Cure parameters, i.e. negative microscopy stain (KOH) examination and a negative fungal culture of the target toenail).The outcome will be assessed via mycological assessment and digital measurement of the area of toenail infection.
• Clinical Efficacy (defined as 0% to less than or equal to 10% area of infection of the target great toenail).The outcome will be assessed via digital measurement of the area of toenail infection.
• Complete Cure (defined as 100% clear nail surface area of the target toenail, in addition to both a negative microscopy stain result and a negative fungal culture result of the target toenail).The outcome will be assessed via mycological assessment and digital measurement of the area of toenail infection.
• A mean change in clear nail surface area from baseline.The outcome will be assessed via digital measurement of the area of toenail infection.

Timepoint [2]

Outcomes will be assessed at weeks 13, 24, 36 and 40 for cohort 2.

Secondary outcome [3]

These are composite secondary outcomes
To determine if five repeated treatment periods of 6 weeks (6 x 42 days) followed by one treatment period of 1 week (7 days; each treatment period separated by a treatment free period of 1 week) for a 36-week period, followed by a 4-week treatment free period, affects rates of Mycological Cure, Complete or Almost Complete Cure and Clinical Efficacy in participants with mild to moderate DLSO of the target great toenail.
1. Percentage of participants in cohort 3 who at Week 13, Week 24, Week 36 and Week 40 following application of 20 mg/mL topical HXP124 achieve:
• Mycological Cure (negative microscopy stain and a negative fungal culture of the target toenail). The outcome will be assessed via mycological assessment.
• Complete or Almost Complete Cure (defined as is less than or equal to 5% but greater than or equal to 0% infection of the target great toenail, in addition to both Mycological Cure parameters, i.e. negative microscopy stain (KOH) examination and a negative fungal culture of the target toenail). The outcome will be assessed via mycological assessment and digital measurement of the area of toenail infection.
• Clinical Efficacy (defined as 0% to less than or equal to 10% area of infection of the target great toenail). The outcome will be assessed via digital measurement of the area of toenail infection.
• Complete Cure (defined as 100% clear nail surface area of the target toenail, in addition to both a negative microscopy stain result and a negative fungal culture result of the target toenail). The outcome will be assessed via mycological assessment and digital measurement of the area of toenail infection.
• A mean change in clear nail surface area from baseline. The outcome will be assessed via digital measurement of the area of toenail infection.

Timepoint [3]

Outcomes will be assessed at Week 13, Week 24, Week 36 and Week 40 for cohort 3.

Secondary outcome [4]

These are composite secondary outcomes.
Change in the rate of Mycological Cure, Complete or Almost Complete Cure and Clinical Efficacy following additional application of once-weekly topical HXP124 (20 mg/mL) for 23 weeks
• Mycological Cure (negative microscopy stain and a negative fungal culture of the target toenail). The outcome will be assessed via mycological assessment.
• Complete or Almost Complete Cure (defined as is less than or equal to 5% but greater than or equal to 0% infection of the target great toenail, in addition to both Mycological Cure parameters, i.e. negative microscopy stain (KOH) examination and a negative fungal culture of the target toenail). The outcome will be assessed via mycological assessment and digital measurement of the area of toenail infection.
• Clinical Efficacy (defined as 0% to less than or equal to 10% area of infection of the target great toenail). The outcome will be assessed via digital measurement of the area of toenail infection.
• Complete Cure (defined as 100% clear nail surface area of the target toenail, in addition to both a negative microscopy stain result and a negative fungal culture result of the target toenail). . The outcome will be assessed via mycological assessment and digital measurement of the area of toenail infection.

Timepoint [4]

Outcomes will be assessed at Week 13, Week 24, Week 36 and Week 40 in cohort 2..

Secondary outcome [5]

Change in clear nail surface area following additional application of once-weekly topical HXP124 (20 mg/mL) for 23 weeks.
The outcome will be assessed via digital measurement of the area of toenail infection.

Timepoint [5]

Outcomes will be assessed at Week 13, Week 24, Week 36 and Week 40 in cohort 2..

Secondary outcome [6]

Change in the rate of Mycological Cure, Complete or Almost Complete Cure and Clinical Efficacy following application of once-daily topical HXP124 (20 mg/mL) for six treatment periods.These are composite secondary outcomes.
• Mycological Cure (negative microscopy stain and a negative fungal culture of the target toenail). The outcome will be assessed via mycological assessment.
• Complete or Almost Complete Cure (defined as is less than or equal to 5% but greater than or equal to 0% infection of the target great toenail, in addition to both Mycological Cure parameters, i.e. negative microscopy stain (KOH) examination and a negative fungal culture of the target toenail). The outcome will be assessed via mycological assessment and digital measurement of the area of toenail infection.
• Clinical Efficacy (defined as 0% to less than or equal to 10% area of infection of the target great toenail). The outcome will be assessed via digital measurement of the area of toenail infection.
• Complete Cure (defined as 100% clear nail surface area of the target toenail, in addition to both a negative microscopy stain result and a negative fungal culture result of the target toenail). The outcome will be assessed via mycological assessment and digital measurement of the area of toenail infection.

Timepoint [6]

Outcomes will be assessed at Week 13, Week 24, Week 36 and Week 40 in cohort 3.

Secondary outcome [7]

Change in clear nail surface area following application of once-daily topical HXP124 (20 mg/mL) for six treatment periods. The outcome will be assessed via digital measurement of the area of toenail infection.

Timepoint [7]

Outcomes will be assessed at Week 13, Week 24, Week 36 and Week 40 in cohort.3.

Secondary outcome [8]

The mean change in clear nail surface area and clear nail growth (change from baseline in unaffected new nail growth) at Week 13, Week 24, Week 36 and Week 40 following application of 20 mg/mL topical HXP124 for participants in each treatment group (all cohorts). The outcome will be assessed via digital measurement of the area of toenail infection and toenail growth.

Timepoint [8]

Outcomes will be assessed at weeks 13, 24, 36 and 40 for all cohorts.

Eligibility

Key inclusion criteria

1. Presence of mild to moderate clinically diagnosed DLSO, defined as involving at least 20% but not more than 60% nail plate involvement of at least one great toenail as determined by visual inspection at screening after the nail has been trimmed;
2. Confirmed diagnosis of onychomycosis by positive mycological microscopic examination (staining by potassium hydroxide (KOH) for dermatophyte hyphae) and positive dermatophyte culture or a mixed culture of dermatophytes/Candida from the target great toenail at screening;
Note: It is known that both cultures and stains may yield false negative results. If the stain
exhibits fungal elements or septate hyphae but the culture fails to grow a fungus, the culture may be repeated. If the culture grows but the stain does not exhibit fungal elements or septate hyphae, the stain may be repeated. If two sequential cultures or two subsequent stains are negative, the nail should not be included in the study.
3. The combined thickness of the distal nail plate at the associated hyperkeratotic nail bed is less than or equal to 3 mm at screening;
4. A clear nail distance of less than or equal to 3 mm from the proximal nail fold at screening;
5. Males and females aged 18-70 years (inclusive) in otherwise good health based on past
medical history, physical examination, vital signs, ECG, and laboratory tests at screening, as determined by the PI;
Note: Participants with Type 2 diabetes mellitus (T2DM) under glycemic control who
manage their condition only by diet/exercise will be considered for study participation, at the discretion of the PI.
6. Negative test for selected drugs of abuse prior to enrollment. A positive result may be
verified by re-testing (up to one false positive result permitted) and may be followed up at
the discretion of the PI;
7. Females must be non-pregnant and non-lactating, and either surgically sterile (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or use a highly effective contraceptive method (oral contraceptives pills (OCP’s), long acting implantable hormones, injectable hormones, a vaginal ring or an intrauterine device (IUD)) from screening until at least 30 days after the last application of study drug or be post-menopausal for less than or equal to 12 months. Post-menopausal status will be confirmed through testing of follicle stimulating hormone (FSH) levels (less than or equal to 40 IU/mL) at screening for amenorrheic female participants. Females who are abstinent from heterosexual intercourse (for the duration of the dosing period plus 1 month) will also be eligible. Female participants in same sex relationships do not need to use contraception;
8. Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and at Day 1 and be willing to have additional pregnancy tests as required throughout the study;
9. Willing and able to provide voluntary signed informed consent prior to study entry;
10. Willing and able to comply with all scheduled visits, laboratory tests, and other study
procedures.

Minimum age

18 Years

Maximum age

70 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Exclusion Criteria
1. Presence of dermatophytoma in the target great toenail;
2. Lunula (matrix) involvement or exclusively lateral disease in the target great toenail;
3. Presence of hyperkeratotic/moccasin-type tinea pedis (athletes’ foot) at screening or baseline visits;
4. Presence of toenail infection other than being caused by dermatophytes and Candida;
5. Previous toenail surgery of the target great toenail;
6. Presence of more than 6 infected toenails and/or any infected fingernails;
7. Presence of any disease or condition other than DLSO that might cause nail abnormalities or interfere with the evaluation of the study drug;
8. Pregnant or lactating female at screening or plans to become pregnant or breastfeed from the time of enrolment until 30 days after the last application of study drug;
9. Use of any systemic antifungal therapy with known activity against dermatophytes within 12 weeks prior to the Screening visit part 1;
10. Non-responsiveness to prior systemic antifungal therapy for onychomycosis;
11. Use of any prescription or over-the-counter topical antifungal therapy for the feet within 4 weeks prior to screening part 1 (does not include topical antifungals for treatment of tinea pedis which can be used during the study);
12. Use of topical anti-inflammatories, corticosteroids and immunomodulators applied to the toe area within 2 weeks of screening part 2. Participants are not excluded for concomitant drugs that inhibit cytochrome P450 3A4;
13. Use of systemic immunomodulators and/or corticosteroids (including intramuscular injections of corticosteroids) within 4 weeks of screening part 2;
14. A history of immunosuppression and/or clinical signs indicative of possible immunosuppression, known human immunodeficiency virus or infection;
15. Use of any investigational or non-registered drug or vaccine within 30 days or 5 half-lives (whichever is longer) preceding treatment period 1 or planned use during the study period;
16. Unwilling to refrain from the use of nail cosmetics such as clear and/or colored nail lacquers from the screening visit until study completion;
17. Diagnosis of Diabetes mellitus which is not stable and controlled by diet/exercise;
18. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the participant inappropriate for entry into this study;
19. Seropositive for HIV or Hepatitis C Virus (HCV) or Hepatitis B surface antigen (HBsAg) positive at screening;
20. History of severe allergy (requiring hospital care), severe reaction to any drug, or any known or suspected allergies or sensitivities to HXP124 or analogous drugs or excipients;
21. History of alcohol or drug abuse that in the opinion of the Investigator could affect the participants’ safety or compliance with study;
22. Participant who, in the judgment of the Investigator, is unwilling or unable to comply with the restrictions described in this protocol.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Other design features

Phase

Phase 2

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

29/06/2020

Actual

9/10/2020

Date of last participant enrolment

Anticipated

19/10/2020

Actual

24/07/2021

Date of last data collection

Anticipated

16/08/2021

Actual

9/05/2022

Sample size

Target

132

Accrual to date

Final

117

Recruitment in Australia

Recruitment state(s)

ACT,NSW,QLD,SA,WA,VIC

Recruitment hospital [1]

Veracity Clinical Research - Woolloongabba

Recruitment hospital [2]

St John of God Hospital, Subiaco - Subiaco

Recruitment hospital [3]

Fremantle Dermatology - Fremantle

Recruitment hospital [4]

Dermatology Institute of Victoria - South Yarra

Recruitment hospital [5]

Skin and Cancer Foundation - Carlton

Recruitment hospital [6]

North Eastern Health Specialists - Hectorville

Recruitment hospital [7]

Paratus Clinical Research - Brisbane - Albion

Recruitment hospital [8]

Paratus Clinical Pty Ltd Blacktown Trial Clinic - Blacktown

Recruitment hospital [9]

Paratus Clinical Pty Ltd Kanwal Trial Clinic - Kanwal

Recruitment hospital [10]

Essendon Private Hospital - Essendon

Recruitment postcode(s) [1]

2148 - Blacktown

Recruitment postcode(s) [2]

2259 - Kanwal

Recruitment postcode(s) [3]

3040 - Essendon

Recruitment postcode(s) [4]

3053 - Carlton

Recruitment postcode(s) [5]

3141 - South Yarra

Recruitment postcode(s) [6]

4010 - Albion

Recruitment postcode(s) [7]

4102 - Woolloongabba

Recruitment postcode(s) [8]

5073 - Hectorville

Recruitment postcode(s) [9]

6008 - Subiaco

Recruitment postcode(s) [10]

6160 - Fremantle

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Auckland

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Hexima Ltd

Address [1]

La Trobe Institute for Molecular Science,
Level 4, LIMS2, La Trobe University,
Melbourne, VIC 3086 Australia

Country [1]

Australia

Primary sponsor type

Commercial sector/Industry

Name

Hexima Ltd

Address

La Trobe Institute for Molecular Science,
Level 4, LIMS2, La Trobe University,
Melbourne, VIC 3086 Australia

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Bellberry

Ethics committee address [1]

123 Glen Osmond Road, Eastwood, South Australia 5063

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

18/03/2020

Approval date [1]

09/04/2020

Ethics approval number [1]

2020-02-170

Summary

Brief summary

This is a multi-center, randomized, double-blind, placebo controlled study designed to assess the efficacy, safety and tolerability of HXP124 when administered topically to the great toenail of otherwise healthy participants with mild to moderate Onychomycosis.
All participants will be instructed to apply HXP124 topical solution or vehicle to one target great toenail and any other infected toenails, following bathing and towel drying.
Up to 132 eligible adult participants will be enrolled to one of three dosing cohorts and will be randomly assigned to receive treatment with either HXP124 topical solution or vehicle (at 3:1

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Peter Foley

Address

Skin Health Institute Inc.
Level 1, 80 Drummond Street
Carlton VIC 3053

Country

Australia

Phone

+61 396239416

Fax

pfoley@skinhealthinstitute.org.au

Contact person for public queries

Name

Dr Yolanda Gaspar

Address

Hexima Ltd
Level 4, Bldg LIMS2 La Trobe University
Bundoora
VIC 3086

Country

Australia

Phone

+61 394793521

Fax

Y.Gaspar@latrobe.edu.au

Contact person for scientific queries

Name

Dr Yolanda Gaspar

Address

Hexima Ltd
Level 4, Bldg LIMS2, La Trobe University
Bundoora
VIC 3086

Country

Australia

Phone

+61 394793521

Fax

Y.Gaspar@latrobe.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Data is intended to be pooled for analysis.

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

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Doc. No.	Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
4148	Plain language summary	No		Please see: ASX announcement 11/7/22 https://i... [More Details]

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Source	Title	Year of Publication	DOI
Dimensions AI	Hyperpolarisation of Mitochondrial Membranes Is a Critical Component of the Antifungal Mechanism of the Plant Defensin, Ppdef1	2024	https://doi.org/10.3390/jof10010054

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