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

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

Detailed Description
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The investigator will determine whether more patients taking serlopitant 5 mg daily as compared to placebo can achieve at least a 3-point reduction in the 24-hour Average Itch Numeric Rating Scale (NRS) following two months of treatment. Secondary objectives include; comparative weekly change in daily worst itch NRS, comparative weekly change in daily average itch NRS, the proportion of patients who achieve at least 30% or 50% reduction in Average Itch NRS at month 2, proportion of patients achieving 2-point and 4-point reductions in Average Itch NRS at month 2, Patient Global Impression of Change (PGIC) at month 2, the change in participant static assessment of itch at month 2, and assessment of the safety of serlopitant in adolescents (≥13 y.o.) and adults with epidermolysis bullosa-related itch.

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

Conditions
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Epidermolysis Bullosa

Intervention / Treatment
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* Drug: Serlopitant Tablet
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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). Are unable or unwilling to maintain their current anti-itch and opioid-based pain medications at a stable dosage through the course of the two months of active treatment (including but not limited to opioid pain medications, antihistamines, and gabapentin) Started or changed medications, creams, or emollients including over-the-counter (OTC) preparations or bath oil treatment specifically for relief of pruritus within 30 days prior to Screening. Within in the past 12 months, have expressed suicidal ideation with some intent to act. Have any social or medical condition (e.g. alcoholism, drug dependency, psychotic state) that, in the investigator's opinion, might interfere with the subject's ability to comply with the requirements of the protocol.

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: 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Oral Tablet<br>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<br>* The placebo is a tablet that looks like a drug but has no drug or other active ingredient in it.<br>* Other names: Sugar pill;|
| Active Comparator: Serlopitant Tablet<br>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<br>* 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.<br>* Other names: VPD-737;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Achieve at Least a 2-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 | 
| Number of Patients Who Achieve at Least a 4-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 | 
| Number of Patients Who Achieve at Least a 30% 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 | 
| Number of Patients Who Achieve at Least a 50% 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 | 
| Weekly Worst Itch NRS | Participants will be asked to complete a daily itch diary with their worst itch numeric rating scale (WI-NRS) over the past 24 hours. Score range: 0 to 10, higher scores mean more itching. | baseline and week 1, 2, 3, 4, 5, 6, 7, and 8 | 
| Weekly 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 week 1, 2, 3, 4, 5, 6, 7, and 8 | 
| Patient Global Impression of Change (PGIC) | PGIC categorized as Very much better, Moderately better, A little better, No change, A little worse, Moderately worse, and Very much worse. | month 2 | 
| Change in Static Participant Assessment of Itch | Severity of itch over past 7 days assessed as Very Severe, Severe, Moderate, Mild, or None. Change is reported as the number of participants with 3-category improvement, 2-category improvement, 1-category improvement, no change, or worse. | month 2 |