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

• ClinicalTrials.gov Identifier: NCT02654483
• Recruitment Status: Completed
• First Posted: January 13, 2016
• Results First Posted: July 2, 2019
• Last Update Posted: July 2, 2019
• Sponsor: Jean Yuh Tang
• Collaborators: Epidermolysis Bullosa Research Partnership; Menlo Therapeutics Inc.
• Information provided by (Responsible Party): Jean Yuh Tang, Stanford University

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Epidermolysis Bullosa; Pruritus	Drug: VPD-737; Other: Placebo	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Research personnel not involved in this study was responsible for blinding. This was the only personnel with access to the code linking study drug bottle numbers to treatment (i.e. active or placebo). The code was broken when all data was captured and locked on an electronic data capture system.
• Primary Purpose: Treatment
• Official Title: A Phase 2 Trial of Neurokinin-1 Receptor Antagonist for the Treatment of Itch in Epidermolysis Bullosa Patients
• Actual Study Start Date: August 31, 2016
• Actual Primary Completion Date: June 28, 2018
• Actual Study Completion Date: July 27, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: 5 mg VPD-737; 5 mg tablets of VPD-737 to be taken daily by mouth for 56 days	Drug: VPD-737; VPD-737 inhibits the receptor neurokinin-1.; Other Name: Serlopitant
Placebo Comparator: Placebo; Placebo tablets to be taken daily by mouth for 56 days	Other: Placebo; Matching tablets to VPD-737 tablets without active drug

Outcome Measures

Primary Outcome Measures :

1. Comparative Weekly Change in NRS Itch Score Over the 8-week Active Treatment Period [ Time Frame: Baseline and 8 weeks ]

   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.

Secondary Outcome Measures :

1. Wound Healing Determination [ Time Frame: Baseline and 8 weeks ]
   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.
2. Change in Mean NRS Itch Score During Bathing/Dressing Changes [ Time Frame: Baseline and 8 weeks ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 13 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Clinical diagnosis of Epidermolysis Bullosa (EB) and pruritus

Exclusion Criteria:

• Chronic liver or renal disease

Contacts and Locations

Locations

United States, California

Stanford

Stanford, California, United States, 94305

Sponsors and Collaborators

Jean Yuh Tang

Epidermolysis Bullosa Research Partnership

Menlo Therapeutics Inc.

Investigators

• Principal Investigator: Jean Tang, MD, PhD; Stanford University

  Study Documents (Full-Text)

Documents provided by Jean Yuh Tang, Stanford University:

Informed Consent Form  [PDF] April 17, 2019

Study Protocol and Statistical Analysis Plan  [PDF] January 9, 2017

More Information

• Responsible Party: Jean Yuh Tang, Associate Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT02654483 History of Changes
• Other Study ID Numbers: 34182
• First Posted: January 13, 2016
• Results First Posted: July 2, 2019
• Last Update Posted: July 2, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Epidermolysis Bullosa; Pruritus; Skin Diseases; Skin Manifestations; Signs and Symptoms; Skin Abnormalities; Congenital Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases, Vesiculobullous; Neurokinin-1 Receptor Antagonists; Neurokinin A; Substance P; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs