Neurokinin-1 Receptor Antagonist for the Treatment of Itch in EB Patients

Study Overview
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Brief Summary
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Our goal is to determine whether daily oral administration of VPD-737 (5 mg) is effective and safe in treating moderate to severe pruritus in patients with Epidermolysis Bullosa (EB).

Detailed Description
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Itch is the most common complaint reported by patients with EB of all subtypes, and there is no current effective treatment. Itch often triggers scratching that creates new wounds and increases EB disease severity. This study aims to target the physiological mechanisms of pruritus (itch) in patients with EB. Substance P is a major mediator of pruritus and binds to the receptor neurokinin-1 (NK1), which is expressed in the central nervous system and the skin. VPD-737 (serlopitant), a novel drug that inhibits the NK1 receptor, has been shown to reduce severe itch in a previous study of 257 adult patients with chronic pruritus. Each patient will be un-blinded individually after completing 3 months of study period. All patients who complete the study will be offered a 2-month period on active drug. Patient who received active drug in the first period will be contacted and asked if they would like to continue on active drug for an additional 2 months. Patients who received placebo in the first period will be contacted and asked if they would like to repeat the study on open label for 2 months.

Official Title
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A Phase 2 Trial of Neurokinin-1 Receptor Antagonist for the Treatment of Itch in Epidermolysis Bullosa Patients

Conditions
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Epidermolysis Bullosa, Pruritus

Intervention / Treatment
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* Drug: VPD-737
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of Epidermolysis Bullosa (EB) and pruritus Exclusion Criteria: Chronic liver or renal disease

Ages Eligible for Study
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Minimum Age: 13 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
Interventional Model Description: Phase 2 investigator-initiated, randomized, double-blind, placebo-controlled, parallel-arm trial evaluating the comparative effect of serlopitant 5 mg by mouth daily versus placebo in treatment of chronic pruritus in pediatric and adult EB patients
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5 mg VPD-737<br>5 mg tablets of VPD-737 to be taken daily by mouth for 56 days | Drug: VPD-737<br>* VPD-737 inhibits the receptor neurokinin-1.<br>* Other names: Serlopitant;|
| Placebo Comparator: Placebo<br>Placebo tablets to be taken daily by mouth for 56 days | Other: Placebo<br>* Matching tablets to VPD-737 tablets without active drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparative Weekly Change in NRS Itch Score Over the 8-week Active Treatment Period | Determine the efficacy of Serlopitant compared with placebo on reducing EB-associated daily itch score as measured by patient self-reports using a numeric rating scale (NRS) for itch severity.The NRS is comprised of one item and represents the numbers 0 (no itch) to 10 (worst imaginable itch). Because itch is subjective and can vary day to day, nightly NRS scores were recorded in patients' Itch Diaries. NRS recorded by subject daily, from screening visit through the end of the study. This study was designed to detect differences between the two treatment groups. The primary endpoint was the comparative weekly change in Numeric Rating Scale (NRS) itch severity score from baseline over 8 weeks; derived from a linear mixed effects model which utilizes observations from both the treatment and placebo groups to generate an interaction term of interest. Itch severity changes from day to day and this model can more appropriately report trends in patients' itch severity with treatment. | Baseline and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wound Healing Determination | Wound dimensions, including length, width, and area (in cm2), will be obtained using the Canfield system. Changes in dimensions between visits as well as changes in dimensions from baseline will be recorded. Overall mean % change from baseline is reported as the secondary endpoint. | Baseline and 8 weeks | 
| Change in Mean NRS Itch Score During Bathing/Dressing Changes | Itch is exacerbated by activities such as dressing changes or bathing. NRS itch score during bathing or dressing in the past 24 hours were collected. Numeric rating scale (NRS) for itch severity is comprised of one item and represents the numbers 0 (no itch) to 10 (worst imaginable itch). This study was designed to detect differences between the two treatment groups. This secondary endpoint was the comparative change in Numeric Rating Scale (NRS) itch severity score during bathing/dressing changes from baseline over 8 weeks as determined by application of a linear mixed effects model. | Baseline and 8 weeks |