Safety, Tolerability and Efficacy of QRX003 Lotion in Subjects With Netherton Syndrome

Study Overview
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Brief Summary
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This study has been designed to determine the safety, tolerability and efficacy of QRX003 lotion 2%, 4% in subjects with Netherton Syndrome (NS) in comparison to vehicle

Official Title
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A Multicenter, Randomized, Vehicle-Controlled, Double-Blind, Parallel Comparison Study of QRX003 Lotion in Subjects With Netherton Syndrome

Conditions
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Netherton Syndrome

Intervention / Treatment
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* Drug: QRX003-2% Lotion
* Drug: QRX003-4% Lotion
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is a male or non-pregnant female at least 18 years of age. Females must be post-menopausal , surgically sterile , or use an effective method of birth control , for the duration of the study and for 3 months following completion of treatment. Women of childbearing potential (WOCBP) must have a negative urine pregnancy test (UPT) at Visit 1/Screening and Visit 2/Baseline. Subject has a clinical diagnosis of NS and agrees to genetic testing at Visit 1/Screening for confirmation of NS diagnosis if the subject does not have test results confirming a SPINK5 mutation. Subject has NS lesions in the Treatment Area (i.e., arms or lower legs). Subject is in good general health and free of any disease state or physical condition that might impair evaluation of NS or exposes the subject to an unacceptable risk by study participation. Exclusion Criteria: Subject is pregnant, lactating, or is planning to become pregnant during the study. Subject has any skin pathology in the Treatment Area or condition that, could interfere with the evaluation of the test article or requires use of interfering topical, systemic, or surgical therapy. Subject has Fridericia-corrected QT ≥ 450 ms for males or ≥ 470 ms for females Subject has active cancer of any type excluding non-melanoma skin cancer outside of the Treatment Area. Subject has diabetes of any type, except non-insulin dependent diabetes mellitus that is reasonably controlled. Subject has evidence of active infection during screening, or serious infection within 30 days prior to Visit 2/Baseline. Subject has known human immunodeficiency virus, hepatitis B or C virus, or active or latent tuberculosis. Subject has used ultraviolet phototherapy within the Treatment Area within 4 weeks prior to Visit 2/Baseline. Subject has used systemic prescription treatment for NS within 4 weeks prior to Visit 2/Baseline. Subject has used systemic biologic therapy for NS. Subject has used topical prescription treatment in the Treatment Area within 2 weeks prior to Visit 2/Baseline. Subject has used any topical bland moisturizers/emollients in the Treatment Area within 24 hours prior to Visit 2/Baseline. Subject is currently enrolled in an investigational drug, biologic, or device study. Subject has used an investigational drug, biologic, or device treatment within 30 days prior to Visit 2/Baseline.

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QRX003-2%<br>Subjects will apply test article once daily in the morning (QAM) for 12 weeks | Drug: QRX003-2% Lotion<br>* QRX003Topical Lotion containing 2% active drug (serine protease inhibitor)<br>|
| Experimental: QRX003-4%<br>Subjects will apply test article once daily in the morning (QAM) for 12 weeks | Drug: QRX003-4% Lotion<br>* QRX003Topical Lotion containing 4% active drug (serine protease inhibitor)<br>|
| Experimental: Vehicle Lotion<br>Subjects will apply test article once daily in the morning (QAM) for 12 weeks | Drug: Vehicle<br>* Vehicle Lotion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Endpoints-1-point IGA | Proportion of subjects with 1-point reduction on the Investigator's Global Assessment (IGA) from Baseline. The IGA assesses overall severity of a subject's NS based on a 5-point scale where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, and 4 = severe. | Up to week 16 | 
| Efficacy Endpoints-2-point IGA | Proportion of subjects with 2-point reduction in IGA from Baseline. | Up to week 16 | 
| Efficacy Endpoints-NS Sign | Change from Baseline in each individual NS Sign (erythema and scaling). Severity of each NS sign is graded on a 5-point scale. | Up to week 16 | 
| Efficacy Endpoints-BSA | Change from Baseline in total Body Surface Area (BSA) affected by NS in the Treatment Area | Up to week 16 | 
| Efficacy Endpoints-WI-NRS score | Change from Baseline in the Worst Itch-Numeric Rating Scale (WI-NRS) score. Itch severity is graded on an 11-point scale where 0 represents no itch and 10 represents worst itch imaginable. | Up to week 16 | 
| Efficacy Endpoints-TSQM | Assessment of subject satisfaction with treatment based on the Treatment Satisfaction Questionnaire for Medication (TSQM). The TSQM measures a subject's level of satisfaction or dissatisfaction with the treatment. Composite scores can range from 0 to 100; higher scores indicate better satisfaction. | Up to week 16 | 
| Efficacy Endpoints-Rescue Therapy | Proportion of subjects requiring rescue therapy | Up to week 16 | 
| Safety Endpoints-AEs | Any local and systemic AEs (Adverse Events)/serious AEs | Up to week 16 | 
| Safety Endpoints-LSR | Number of subjects with presence of the following LSRs (Local Skin Reactions): edema, excoriations, oozing/vesiculation/crusting, and erosions at any study visit. | Up to week 16 |