CompletedPhase 2ACTRN12620000697987

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

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.

Sponsor

Hexima Ltd

Enrollment

132 participants

Start Date

Oct 9, 2020

Study Type

Interventional

Conditions

Toenail Onychomycosis

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

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 70 Yearss

Inclusion Criteria18

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;
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.
The combined thickness of the distal nail plate at the associated hyperkeratotic nail bed is less than or equal to 3 mm at screening;
A clear nail distance of less than or equal to 3 mm from the proximal nail fold at screening;
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.
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;
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;
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;
Willing and able to provide voluntary signed informed consent prior to study entry;
Willing and able to comply with all scheduled visits, laboratory tests, and other study
procedures.

Exclusion Criteria22

Presence of dermatophytoma in the target great toenail;
Lunula (matrix) involvement or exclusively lateral disease in the target great toenail;
Presence of hyperkeratotic/moccasin-type tinea pedis (athletes’ foot) at screening or baseline visits;
Presence of toenail infection other than being caused by dermatophytes and Candida;
Previous toenail surgery of the target great toenail;
Presence of more than 6 infected toenails and/or any infected fingernails;
Presence of any disease or condition other than DLSO that might cause nail abnormalities or interfere with the evaluation of the study drug;
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;
Use of any systemic antifungal therapy with known activity against dermatophytes within 12 weeks prior to the Screening visit part 1;
Non-responsiveness to prior systemic antifungal therapy for onychomycosis;
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);
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;
Use of systemic immunomodulators and/or corticosteroids (including intramuscular injections of corticosteroids) within 4 weeks of screening part 2;
A history of immunosuppression and/or clinical signs indicative of possible immunosuppression, known human immunodeficiency virus or infection;
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;
Unwilling to refrain from the use of nail cosmetics such as clear and/or colored nail lacquers from the screening visit until study completion;
Diagnosis of Diabetes mellitus which is not stable and controlled by diet/exercise;
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;
Seropositive for HIV or Hepatitis C Virus (HCV) or Hepatitis B surface antigen (HBsAg) positive at screening;
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;
History of alcohol or drug abuse that in the opinion of the Investigator could affect the participants’ safety or compliance with study;
Participant who, in the judgment of the Investigator, is unwilling or unable to comply with the restrictions described in this protocol.

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Interventions

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

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.