A Vehicle-controlled Study of Topical MOB015B in the Treatment of Distal Subungual Onychomycosis (DSO)

Study Overview
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Brief Summary
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This is a Phase 3 multicenter, double-blind study to evaluate the safety and efficacy of vehicle-controlled topical MOB015B in the treatment of Distal Subungual Onychomycosis (DSO)

Detailed Description
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Distal subungual onychomycosis (DSO) is the most common form of Onychomycosis, in which fungi invade the underside of the nail plate. The infection may worsen, spread to other uninfected areas or infect other people. Without treatment the disease may have an impact on an individual's quality of life. MOB015B is a newly developed topical solution for the treatment of nail fungus (onychomycosis) containing the active antifungal ingredient terbinafine. All ingredients in MOB015B have a well-established use in approved pharmaceuticals for dermatological use. The purpose of this study is to evaluate the efficacy and safety of a new reduced dose treatment regimen of MOB015B whereby the investigational medicinal product (IMP) is applied daily for 8 weeks and then reduced to once weekly treatment for 40 weeks.

Official Title
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A Multi-center, Double-blind, Randomized, Vehicle-controlled Study of Efficacy and Safety of Topical MOB015B in the Treatment of Mild to Moderate Distal Subungual Onychomycosis (DSO)

Conditions
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Onychomycosis

Intervention / Treatment
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* Drug: MOB015B
* Drug: Vehicle (Placebo Comparator)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females 12 to 75 years of age Distal subungual onychomycosis of at least one of the great toenail(s) affecting 20% to 60% of the target great toenail (verified by a central blinded assessor before randomization) Positive KOH microscopy and culture for dermatophytes in the target toenail Ability of the great toenail to grow (e.g., subject reports cutting toenails at least monthly) Signed written informed consent and assent (if applicable) Exclusion Criteria: Proximal subungual onychomycosis, superficial white onychomycosis, or significant dystrophy judged clinically by the blinded assessor or by the Investigator that may interfere with clinical evaluation of onychomycosis Distal subungual onychomycosis where disease involvement has extended into the proximal portion of the target toenail and the unaffected proximal nail is less than 3 mm measured from proximal nail fold Target toenail thickness more than 3 mm measured at the distal end Spike of onychomycosis extending to eponychium of the target toenail Presence of dermatophytoma (defined as thick masses of fungal hyphae and necrotic keratin) or severe onychorrhexis on the target toenail Nail conditions other than DSO that are known to cause abnormal nail appearance, presence of melanonychia or subungual hematoma that could obscure visualization of nail clearing Other microbial infections of the target toenail, for example, candida or mold infections without isolation of a dermatophyte Previous target toenail surgery (within 6 months) with any residual disfigurement that will impact efficacy outcome or will not allow nail to grow normally, as judged by the Investigator Topical treatment of the toenails with other antifungal medication within 6 weeks before Screening/Visit 1 History of failing oral therapy for onychomycosis within the past 3 years, or inability for nail to appear normal due to trauma, as judged by the Investigator Systemic use of antifungal treatment within 6 months before Screening/Visit 1 Moderate to severe moccasin tinea pedis that require prolonged topical antifungal treatment or oral antifungal treatment should be excluded. Subjects with symptomatic interdigital tinea pedis or mild moccasin type tinea pedis will be screen failed. However, However, they will be allowed to enter the study after appropriate effective treatment and washout period as per Investigator judgment. Signs of severe peripheral circulatory insufficiency as determined by significantly diminished/lack of pedal pulse on either foot Subjects with a current or past history of psoriasis and/or lichen planus Subjects with poorly controlled (or uncontrolled) diabetes mellitus as determined by HbA1c of > 8% Known immunodeficiency, i.e., congenital immunodeficiency, acquired immunodeficiency, iatrogenic by immunosuppressive drugs like cytostatics or by radiation therapy or immunomodulatory medications (e.g., TNF inhibitors) Participation in another clinical trial with an investigational drug or device during the previous 3 months before enrollment/baseline and for the duration of this study Known allergy to any of the tested treatment products Female subjects who are pregnant or breastfeeding; or intend to conceive a child during the duration of the study (52 weeks). Subjects previously randomized to any study involving MOB015B treatment/exposure History of, or current drug or alcohol abuse that would interfere with a subject's ability to participate in the study as determined by the Investigator Psychiatric condition that might limit the participation in the study and/or that lead to the assumption that the subject's ability to completely understand the consequences of consent is missing Close affiliation with the Investigator (e.g., a close relative) or persons working at the same study site, or subject who is an employee of the Sponsor/designee Subjects who are institutionalized because of legal or regulatory order Any diseases or circumstances in which the subject should not participate in the study in the opinion of the Investigator

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MOB015B<br>Applied at bedtime daily for 8 weeks and then reduced to once weekly for 40 weeks | Drug: MOB015B<br>* Applied topically for 48 weeks<br>|
| Placebo Comparator: Control Arm<br>Applied at bedtime daily for 8 weeks and then reduced to once weekly for 40 weeks | Drug: Vehicle (Placebo Comparator)<br>* Applied topically for 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with complete cure of the target toenail | Defined as negative fungal culture of dermatophytes, negative direct potassium hydroxide [KOH] microscopy and 0% clinical disease involvement | 52 Week | 
| Incidence of adverse events (Safety) | Safety as determined by the incidence of adverse events (AEs) | 52 Week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with mycological cure of target toenail | Defined as negative fungal culture of dermatophytes and negative direct KOH microscopy) | 52 Week | 
| Proportion of subjects with treatment success of target toenail | Defined as nails that are completely clear or almost clear of clinical diseases and negative mycology | 52 Week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nail Fungus, Antifungal, Terbinafine, Distal Subungual Onychomycosis (DSO)