A Neurokinin-1 Receptor Antagonist for the Treatment of Pruritus in Patients With Epidermolysis Bullosa

NCT03836001 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 49084
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

To determine if Serlopitant (when taken by mouth) is safe and works on itch in patients aged 13 and above with EB.

Conditions

Epidermolysis Bullosa

Outcome Measures

Primary Outcomes (1)

• Number of Patients Who Achieve at Least a 3-point Reduction in AI-NRS.

  Participants will be asked to complete a daily itch diary with their average itch numeric rating scale (AI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching.

  baseline and after two months of treatment

Secondary Outcomes (8)

• Number of Patients Who Achieve at Least a 2-point Reduction in AI-NRS.

  baseline and after two months of treatment

• Number of Patients Who Achieve at Least a 4-point Reduction in AI-NRS.

  baseline and after two months of treatment

• Number of Patients Who Achieve at Least a 30% Reduction in AI-NRS.

  baseline and after two months of treatment

• Number of Patients Who Achieve at Least a 50% Reduction in AI-NRS.

  baseline and after two months of treatment

• Weekly Worst Itch NRS

  baseline and week 1, 2, 3, 4, 5, 6, 7, and 8

Study Arms (2)

Placebo Oral Tablet

PLACEBO COMPARATOR

Participants will undergo two months of dosing with a placebo (inactive drug or sugar pill), followed by one month of washout. After the washout period, all participants were invited to participate in an open-label extension study with serlopitant 5 mg daily. The duration of the open-label extension study was either 12 months (for those who enrolled before May 2020) or 3 months (for those who registered after May 2020) due to drug availability.

Drug: Placebo Oral Tablet

Serlopitant Tablet

ACTIVE COMPARATOR

Participants will undergo two months of Serlopitant 5mg daily per oral, followed by one month of washout. After the washout period, all participants were invited to participate in an open-label extension study with serlopitant 5 mg daily. The duration of the open-label extension study was either 12 months (for those who enrolled before May 2020) or 3 months (for those who registered after May 2020) due to drug availability.

Drug: Serlopitant Tablet

Interventions

Serlopitant Tablet DRUG

Serlopitant is a small molecule, highly selective NK1-R (neurokinin-1 receptor) antagonist. Two critical mediators of the urge to scratch are Substance P, or SP, and its receptor, NK1-R. SP is a naturally occurring peptide in the tachykinin neuropeptide family. Tachykinins have a broad range of functions in the nervous and immune systems. SP binding of NK1-R has been shown to be a key mediator of sensory nerve signaling, including the itch-scratch reflex and the vomiting reflex.

Also known as: VPD-737

Serlopitant Tablet

Placebo Oral Tablet DRUG

The placebo is a tablet that looks like a drug but has no drug or other active ingredient in it.

Also known as: Sugar pill

Placebo Oral Tablet

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females who are at least 13 years of age.
• Willing and able to understand and sign informed assent/consent. Adolescents will need a parent or guardian willing and able to give consent.
• Clinical diagnosis of epidermolysis bullosa (dystrophic, junctional or simplex).
• History of chronic pruritus of at least 6 weeks in duration
• On the Screening Visit or Screening phone call, patients must have an NRS pruritus score of at least 5 on average itch score in the past 24 hours
• Female subjects must be of non-childbearing potential (ie, post-menopausal for at least 1 year, had a hysterectomy, or had a tubal ligation) or, if of childbearing potential, must have a confirmed negative urine pregnancy test prior to study treatment and be willing to use effective contraception for the duration of the trial. Effective contraception is defined as follows: oral/implant/injectable/ transdermal contraceptives, intrauterine device, condom with spermicide, or diaphragm with spermicide. Abstinence or partner's vasectomy is acceptable if the female agrees to use effective contraception if she decides to discontinue abstinence or to have sexual intercourse with a non-vasectomized partner.
• Judged to be in good health based upon the results of a physical examination, medical history, and safety laboratory tests.

You may not qualify if:

• Have any medical condition or disability that would interfere with the assessment of safety or efficacy in this trial or would compromise the ability of the subject to travel to Stanford or to undergo study procedures or to give informed consent.
• Have a history of sensitivity to any components of the study material.
• Are females of childbearing potential who are unwilling to use adequate contraception or who are breast feeding.
• Have any chronic or acute medical condition that, in the opinion of the investigator, might interfere with the study results or place the subject at undue risk.
• Have chronic renal disease, i.e., serum creatinine greater than 2 times the upper limit of normal.
• Have chronic liver disease. Subjects with hepatitis B and C who have normal liver function may be enrolled.
• Have a current malignancy (such as Hodgkin's lymphoma, B or T cell lymphoma, or myeloma) or blood cell dyscrasia (e.g., polycythemia or myelofibrosis) that would lead to systemic chronic pruritus.
• Have a history of thyroid cancer, thyroid nodules, inadequately treated thyroid disease, or abnormal TSH or free T4 at screening.
• Have a history of abnormalities in adrenal or pituitary function (pituitary adenoma, adrenal insufficiency, or adrenal nodule).
• Screening cortisol level \< 3 mcg/dL
• Unevaluated abnormalities in cortisol, ACTH, or prolactin.
• Have pruritus of psychogenic etiology (delusions of parasitosis, obsessive compulsive disorder and major depression) or neuropathic etiology (due to shingles, spinal cord injury or with neurologic deficit).
• Have pruritus due to urticaria, drug allergy, or infection (such as pityriasis rosacea or tinea or active human immunodeficiency virus \[HIV\]). Note: Subjects with HIV who have undetectable viral load, and stable retro-viral therapy may enroll.
• Have taken investigational medications within 30 days prior to Screening.
• Are unwilling to discontinue specific medications that, in the view of the investigator may have significant interactions with the trial drug, for at least two weeks prior to initiation of study and throughout the study period (this includes miconazole, delavirdine, conivaptan, Clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir).

Sponsors & Collaborators

• Stanford University: lead
• Epidermolysis Bullosa Research Partnership: collaborator
• Vyne Therapeutics Inc.: collaborator

Study Sites (1)

Stanford University

Redwood City, California, 94063, United States

Location

Related Publications (1)

• Chiou AS, Choi S, Barriga M, Dutt-Singkh Y, Solis DC, Nazaroff J, Bailey-Healy I, Li S, Shu K, Joing M, Kwon P, Tang JY. Phase 2 trial of a neurokinin-1 receptor antagonist for the treatment of chronic itch in patients with epidermolysis bullosa: A randomized clinical trial. J Am Acad Dermatol. 2020 Jun;82(6):1415-1421. doi: 10.1016/j.jaad.2019.09.014. Epub 2019 Sep 18.

  PMID: 31541747 DERIVED

MeSH Terms

Conditions

Epidermolysis Bullosa

Interventions

serlopitant; Sugars

Condition Hierarchy (Ancestors)

Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Vesiculobullous

Intervention Hierarchy (Ancestors)

Carbohydrates

Limitations and Caveats

The primary limitation of the study is the small sample size due to the rarity of EB, the COVID-19 pandemic-related disruptions, and limited drug availability.

Results Point of Contact

• Title: Albert Chiou
• Organization: Stanford University

achiou@stanford.edu

(650) 721-8418

Study Officials

• Albert S Chiou, MD/MBA

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Dermatology.

Model Details: This is an investigator-initiated, single-center, randomized, double-blind, placebo-controlled, parallel-arm trial evaluating the effects of serlopitant at 5 mg by mouth daily on EB-related itch.

Study Record Dates

• First Submitted: February 7, 2019
• First Posted: February 11, 2019
• Study Start: April 18, 2019
• Primary Completion: December 6, 2021
• Study Completion: June 24, 2022
• Last Updated: February 14, 2023
• Results First Posted: December 23, 2022

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)