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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] 301159 0
None
Universal Trial Number (UTN)
U1111-1255-3850
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Toenail Onychomycosis 317282 0
Condition category
Condition code
Infection 315404 315404 0 0
Other infectious diseases
Skin 315405 315405 0 0
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] 317468 0
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] 323657 0
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] 323657 0
Outcomes will be assessed at weeks 13, 24, 36 and 40 for all cohorts.
Secondary outcome [1] 382508 0
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] 382508 0
Outcomes will be assessed at weeks 13, 24, 36 and 40 for all cohorts.
Secondary outcome [2] 382509 0
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] 382509 0
Outcomes will be assessed at weeks 13, 24, 36 and 40 for cohort 2.
Secondary outcome [3] 383301 0
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] 383301 0
Outcomes will be assessed at Week 13, Week 24, Week 36 and Week 40 for cohort 3.
Secondary outcome [4] 383302 0
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] 383302 0
Outcomes will be assessed at Week 13, Week 24, Week 36 and Week 40 in cohort 2..
Secondary outcome [5] 383303 0
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] 383303 0
Outcomes will be assessed at Week 13, Week 24, Week 36 and Week 40 in cohort 2..
Secondary outcome [6] 383304 0
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] 383304 0
Outcomes will be assessed at Week 13, Week 24, Week 36 and Week 40 in cohort 3.
Secondary outcome [7] 383305 0
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] 383305 0
Outcomes will be assessed at Week 13, Week 24, Week 36 and Week 40 in cohort.3.
Secondary outcome [8] 383966 0
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] 383966 0
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?
No
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] 22951 0
Veracity Clinical Research - Woolloongabba
Recruitment hospital [2] 22952 0
St John of God Hospital, Subiaco - Subiaco
Recruitment hospital [3] 22953 0
Fremantle Dermatology - Fremantle
Recruitment hospital [4] 22954 0
Dermatology Institute of Victoria - South Yarra
Recruitment hospital [5] 22955 0
Skin and Cancer Foundation - Carlton
Recruitment hospital [6] 22956 0
North Eastern Health Specialists - Hectorville
Recruitment hospital [7] 22957 0
Paratus Clinical Research - Brisbane - Albion
Recruitment hospital [8] 22958 0
Paratus Clinical Pty Ltd Blacktown Trial Clinic - Blacktown
Recruitment hospital [9] 22959 0
Paratus Clinical Pty Ltd Kanwal Trial Clinic - Kanwal
Recruitment hospital [10] 22960 0
Essendon Private Hospital - Essendon
Recruitment postcode(s) [1] 38257 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 38258 0
6008 - Subiaco
Recruitment postcode(s) [3] 38259 0
6160 - Fremantle
Recruitment postcode(s) [4] 38260 0
3141 - South Yarra
Recruitment postcode(s) [5] 38261 0
3053 - Carlton
Recruitment postcode(s) [6] 38262 0
5073 - Hectorville
Recruitment postcode(s) [7] 38263 0
4010 - Albion
Recruitment postcode(s) [8] 38264 0
2148 - Blacktown
Recruitment postcode(s) [9] 38265 0
2259 - Kanwal
Recruitment postcode(s) [10] 38266 0
3040 - Essendon
Recruitment outside Australia
Country [1] 24949 0
New Zealand
State/province [1] 24949 0
Auckland

Funding & Sponsors
Funding source category [1] 305602 0
Commercial sector/Industry
Name [1] 305602 0
Hexima Ltd
Country [1] 305602 0
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] 306016 0
None
Name [1] 306016 0
Address [1] 306016 0
Country [1] 306016 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305900 0
Bellberry
Ethics committee address [1] 305900 0
123 Glen Osmond Road, Eastwood, South Australia 5063
Ethics committee country [1] 305900 0
Australia
Date submitted for ethics approval [1] 305900 0
18/03/2020
Approval date [1] 305900 0
09/04/2020
Ethics approval number [1] 305900 0
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 101990 0
A/Prof Peter Foley
Address 101990 0
Skin Health Institute Inc.
Level 1, 80 Drummond Street
Carlton VIC 3053
Country 101990 0
Australia
Phone 101990 0
+61 396239416
Fax 101990 0
Email 101990 0
[email protected]
Contact person for public queries
Name 101991 0
Yolanda Gaspar
Address 101991 0
Hexima Ltd
Level 4, Bldg LIMS2 La Trobe University
Bundoora
VIC 3086
Country 101991 0
Australia
Phone 101991 0
+61 394793521
Fax 101991 0
Email 101991 0
[email protected]
Contact person for scientific queries
Name 101992 0
Yolanda Gaspar
Address 101992 0
Hexima Ltd
Level 4, Bldg LIMS2, La Trobe University
Bundoora
VIC 3086
Country 101992 0
Australia
Phone 101992 0
+61 394793521
Fax 101992 0
Email 101992 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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



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4148Plain language summaryNo Please see: ASX announcement 11/7/22 https://i... [More Details]

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SourceTitleYear of PublicationDOI
Dimensions AIHyperpolarisation of Mitochondrial Membranes Is a Critical Component of the Antifungal Mechanism of the Plant Defensin, Ppdef12024https://doi.org/10.3390/jof10010054
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