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Trial registered on ANZCTR


Registration number
ACTRN12618000131257
Ethics application status
Approved
Date submitted
8/12/2017
Date registered
30/01/2018
Date last updated
11/08/2022
Date data sharing statement initially provided
11/08/2022
Date results provided
11/08/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Evaluation of HXP124 in the treatment of a fungal nail infection, onychomycosis.
Scientific title
Phase I, First in Human (FIH), Randomised, Double-Blind, Placebo-Controlled Multiple Ascending Dose Study in Healthy Volunteers with Mild to Moderate Onychomycosis.
Secondary ID [1] 293430 0
NIL
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
toenails onychomycosis 305595 0
Condition category
Condition code
Infection 304816 304816 0 0
Other infectious diseases
Skin 304817 304817 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
HXP124
Dose:
20ul per application per toe and all toenails on both feet will be applied regardless of how many infected toenails
Part 1 - Multiple ascending dose study, 6 participants (4 active, 2 placebo) per cohort
Cohort 1: 5mg/ml per application
Cohort 2: 10mg/ml per application
Cohort 3: 20mg/ml per application
Part2: single dose study, 30 participants (24 active, 6 placebo)
Cohort 4: dose level to be determined from Part 1.

Duration:
once daily for 42 days

Mode of administration:
Topical by brush

Method of monitor adherence:
Follow up the patients on week 1, 2, 6, 9 and 12, and participants will be given a diary card to record the time of drug application each day. Patients will also receive text messages on their phones daily as reminders to apply drug every day and their clinic appointments.

Duration of treatment:
42 days

Follow up duration:
Part 1: 12 weeks
Part2: 52 weeks
Intervention code [1] 299672 0
Treatment: Drugs
Comparator / control treatment
The excipients in topical solution without the active investigational product in the same bottle as the active.
Control group
Placebo

Outcomes
Primary outcome [1] 304030 0
Assessment of safety and tolerability of multiple ascending doses of HXP124 in participants with mild to moderate onychomycosis.
Timepoint [1] 304030 0
Throughout the study of Part 1 and Part 2, routine clinical tests will be conducted which includes the physical examinations, electrocardiograms (ECGs), vital signs, clinical laboratory results, pain, erythema and local irritation and adverse events.

For Part 1, vital signs and adverse events will be recorded prior to first dose, and 0.5, 1, 3, 5, 7, 10, 15 and 24 hours and Day 7, 14, 42, 63 and 84 following dosing. Physical examination will be conducted prior to first dose, 24 hours, Day 7, 14, 42, 63 and 84 following dosing. ECG will be carried out prior to dosing and on Day 7, 14, 42, 63, and 84 after dosing. Pain, erythema and irritation assessment will be performed prior to the first dosing and 1 hour, 7 hours, 24 hours and on Day 7, 14, 42, 63 and 84 following the first dose. Blood samples will be collected prior to the first dose and on Day 7, 14, 42, 63 and 84 following the first dose for clinical laboratory testing.

For Part 2, vital signs and adverse events will be recorded prior to first dose, and every 30 minutes within the first 4 hours and Day 3, 7, 14, 42, 63 and 84 following dosing. Physical examination and ECG will be conducted prior to first dose and on Day 3, 7, 14, 42, 63 and 84 following the first dose. Pain, erythema and irritation assessment will be performed prior to the first dosing, 4 hours after dosing and on Day 3, 7, 14, 42, 63 and 84 from the first dose. Blood samples will be collected for clinical laboratory testing prior to the first dose and on Day 7, 14, 42, 63 and 84 from the first dose.
Secondary outcome [1] 340887 0
Assess the pharmacokinetic (PK) parameters Cmax, Tmax, and AUClast (and kel, T1/2, AUC0-inf, and CL/F and Vz/F) and Ctrough after single and repeated topical doses of HXP124.
Timepoint [1] 340887 0
For Part 1, blood samples will be collected for PK analysis prior to first dose, and 0.5, 1, 3, 5, 7, 10, 15 and 24 hours and Day 7, 14 and 42 following the first dose. For Part 2, blood samples will be collected for PK analysis prior to first dose, and on Day 3, 7, 14 and 42 following the first dose.
Secondary outcome [2] 341165 0
Plasma HXP124 PK trough concentrations during multiple dosing.
Timepoint [2] 341165 0
For part 1, PK trough levels will be determine before dosing on Day7, 14 and 42. For Part 2, PK trough levels will be determine before dosing on Day 3, 7, 14 and 42.
Secondary outcome [3] 341166 0
Mycological evaluation of the affected great toenail(s) where HXP124 is applied at baseline (before the first dose) will be assessed by visual inspection of the affected toenails, mycological staining and culture.
Timepoint [3] 341166 0
For Part 1 and 2, evaluation will be prior to the first dose and on Day 14, 42, 63 and 84 following the first dose.
Secondary outcome [4] 341167 0
Difference in the appearance of the affected great toenail(s) as determined by photographs throughout treatment and follow-up.
Timepoint [4] 341167 0
For Part 1 and 2, photographs and physical examination of toenails will be conducted prior to the first dose and on Day 7, 14, 42, 63 and 84 following the first dose. Only in Part 2, photographs and physical examination of toenails will also be one on Day 365 after the first dose.
Secondary outcome [5] 341168 0
Determination of the length and surface area of clear nail growth on the affected great toenail(s) from photographs. This is a composite secondary outcome.
Timepoint [5] 341168 0
For Part 1, assessment will be done on the affected great toenail(s) where HXP124 is being applied at week 1 (7 days), week 2 (14 days), week 7 (Day 42). Further assessments will be performed during follow-up visits at week 9 (Day 63), week 12 (Day 84) and, for Part 2 participants only, week 52 (Day 365) compared to baseline from photographs taken.

Eligibility
Key inclusion criteria
1. Confirmation of onychomycosis by mycological staining and/or culture from affected great toenail(s).
2. Appearance of onychomycosis involving at least 20% but not more than 70% of one (or both) affected Great toenail(s) as determined by visual inspection after the nail has been trimmed.
2. The combined thickness of the distal nail plate at the associated hyperkeratotic nail bed is < 3 mm.
3. Adult male and females, 18 to 65 years of age (inclusive) at the time of screening.
4. Medically healthy with clinically insignificant screening results (e.g. laboratory profiles, medical history, ECGs, physical exam), as judged by the PI.
5. Negative urine drug screen/alcohol breath test at screening and Day 1.
6. Voluntary consent to participate in the study.
7. Body Mass Index (BMI) between 17.5 and 35 inclusive.
8. Participants must be instructed to use a highly effective, double barrier contraception (both male and female partners) during the study and for 1 month (females) and 3 months (males) following the final dose of HXP124.
Double barrier contraception is defined as a condom AND one other form of the following:
a. Birth control pills (The Pill)
b. Depot or injectable birth control
c. IUD (Intrauterine Device)
d. Birth Control Patch (e.g., Ortho Evra)
e. NuvaRing®
OR
f. Surgical sterilisation at least 6 months prior to screening visit. i.e., tubal ligation or hysterectomy for women or vasectomy for men.
9. Males must not donate sperm for at least 3 months post-dose of the last study treatment. Male partners of female participants and female partners of male participants must also use contraception, if they are of childbearing potential. Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 1. Females not of childbearing potential must be post-menopausal (defined as cessation of regular menstrual periods for at least 12 months), confirmed by follicle stimulating hormone (FSH) level > 40 mIU/mL.
Rhythm methods will not be considered as highly effective methods of birth control. Participant abstinence for the duration of the study and for 1 month (females) and 3 months (males) after the last dose of HXP124 is acceptable.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of allergy to any of the excipients in HXP124.
2. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
3. Have any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the participant will comply with the study.
4. Females who are pregnant or lactating.
5. Unwilling to refrain from the use of nail cosmetics such as clear and/or coloured nail lacquers from the screening visit until the end of the study.
6. Administration of investigational product (IP) in another trial within 30 days prior to the first study drug administration.
7. Failure to satisfy the principal investigator (PI) of fitness to participate for any other reason.
8. Clinically significant laboratory abnormalities that would interfere with the conduct or interpretation of the study or jeopardise his/her safety.
9. Diabetes mellitus requiring treatment other than diet and exercise.
10. Has not undergone the specified washout period(s) for the following topical preparations or if the participant requires the concurrent use of any of the following topical medications:
a. Topical antifungal applied to the feet (does not include antifungals for treatment of Tinea pedis during the study: 4 weeks)
b. Anti-inflammatories, corticosteroids, topical immunomodulators: 2 weeks
11. Has not undergone the specified washout period(s) for the following systemic medications or the subject requires the concurrent use of any of the following systemic medications:
a. Corticosteroids (including intramuscular injections): 2 weeks
b. Antifungals for treatment of onychomycosis or any systemic antifungal
with known activity against dermatophyte: 12 weeks
12. Use of systemic immunomodulators in the past 4 weeks.
13. Nail or anatomic abnormalities of the toe, e.g., genetic nail disorders, primentary disorders, onychogryphosis, trauma to the nail(s) to be treated.

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by statistical software.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
.
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
22/01/2018
Date of last participant enrolment
Anticipated
19/05/2018
Actual
25/09/2018
Date of last data collection
Anticipated
19/05/2019
Actual
24/09/2019
Sample size
Target
48
Accrual to date
Final
48
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 298057 0
Commercial sector/Industry
Name [1] 298057 0
Hexima Ltd
Country [1] 298057 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] 297131 0
None
Name [1] 297131 0
Address [1] 297131 0
Country [1] 297131 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299076 0
Bellberry
Ethics committee address [1] 299076 0
Ethics committee country [1] 299076 0
Australia
Date submitted for ethics approval [1] 299076 0
18/10/2017
Approval date [1] 299076 0
16/11/2017
Ethics approval number [1] 299076 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 79214 0
Dr Peter Schrader
Address 79214 0
Linear Clinical Research
Level 1, B Block, QEII Medical Centre, Hospital Avenue
Nedlands WA 6009
Country 79214 0
Australia
Phone 79214 0
+61 (0) 8 6382 5100
Fax 79214 0
Email 79214 0
pschrader@linear.org.au
Contact person for public queries
Name 79215 0
Liisa Bevan
Address 79215 0
Linear Clinical Research
Level 1, B Block, QEII Medical Centre, Hospital Avenue
Nedlands WA 6009
Country 79215 0
Australia
Phone 79215 0
+61 (0) 8 6382 5119
Fax 79215 0
Email 79215 0
lbevan@linear.org.au
Contact person for scientific queries
Name 79216 0
Peter Schrader
Address 79216 0
Linear Clinical Research
Level 1, B Block, QEII Medical Centre, Hospital Avenue
Nedlands WA 6009
Country 79216 0
Australia
Phone 79216 0
+61 (0) 8 6382 5100
Fax 79216 0
Email 79216 0
pschrader@linear.org.au

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


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Basic resultsNo 374039-(Uploaded-15-08-2022-16-05-10)-Basic results summary.docx
Plain language summaryNo Summary of Results and Conclusions: Demographic a... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIDefensin–lipid interactions in membrane targeting: mechanisms of action and opportunities for the development of antimicrobial and anticancer therapeutics2022https://doi.org/10.1042/bst20200884
Dimensions AIHyperpolarisation of Mitochondrial Membranes Is a Critical Component of the Antifungal Mechanism of the Plant Defensin, Ppdef12024https://doi.org/10.3390/jof10010054
N.B. These documents automatically identified may not have been verified by the study sponsor.