Study of the Efficacy, Safety and Tolerability of Serlopitant for the Treatment of Pruritus (Itch) With Prurigo Nodularis

Study Overview
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Brief Summary
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Study of the efficacy, safety, and tolerability of serlopitant for the treatment of pruritus in adults with prurigo nodularis

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety, and Tolerability of Serlopitant for the Treatment of Pruritus in Adults With Prurigo Nodularis

Conditions
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Pruritus, Prurigo Nodularis

Intervention / Treatment
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* Drug: 5mg Serlopitant Tablets
* Drug: Placebo Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Subjects must meet the following criteria to be randomized into the study: Male or female, age 18 years or older at consent. Prurigo nodularis (PN), with at least ten nodules on at least two different body surface areas. Idiopathic PN, or an identified pruritic condition associated with the PN with persistent pruritus despite at least 6 weeks of optimized and stable treatment of the underlying condition. The worst pruritus is identified as within the areas of the PN lesions, with a Worst-Itch Numeric Rating Scale (WI-NRS) score in the 24-hour period prior to the Screening visit, and average weekly WI-NRS score in each of the 2 weeks prior to Baseline visit indicating an appropriate pruritus level for the study. Female subjects of childbearing potential must be willing to practice highly effective contraception until 5 weeks after last dose of study drug. Willing and able to complete daily eDiary entries within a consistent timeframe for the duration of the study. Willing and able to comply with study visits and study related requirements including providing written informed consent. Exclusion Criteria (Subjects who meet any of the following criteria are not eligible for participation in the study): Prior treatment with serlopitant. Active pruritic skin disease, other than PN, within 6 months (with the exception of acute dermatoses such as contact dermatitis, sunburn, viral exanthem, which have been resolved for longer than 4 weeks). Treatment with any of the following therapies within 4 weeks. Other neurokinin-1 receptor antagonists (e.g., aprepitant, fosaprepitant, rolapitant). Systemic or topical immunosuppressive/immunomodulatory therapies. Systemic therapies with recognized anti-pruritic properties. Strong cytochrome-P 3A4 inhibitors. Use of an indoor tanning facility, or natural sun exposure resulting in significant tanning or sunburn. Treatment with topical anti-pruritic therapies within 2 weeks. Treatment with biologic therapies within 8 weeks or 5 half-lives, whichever is longer. Treatment with any investigational therapy within 4 weeks (8 weeks for investigational biologic therapies) or 5 half-lives, whichever is longer. Serum creatinine, total bilirubin, alanine aminotransferase or aspartate aminotransferase > 2.5 times the upper limit of normal during screening. Untreated or inadequately treated thyroid adrenal, or pituitary nodules or disease, or history of thyroid malignancy. Malignancy within 5 years prior to enrollment (exception for non-melanoma cutaneous malignancies). Relevant major psychiatric diagnosis in the past 3 years, such as major depressive disorder, bipolar disorder, schizophrenia, psychotic disorder, intellectual disability, severe alcohol use disorder. Documented history of parasitic infection, including skin parasites such as scabies, within 8 weeks. Any medical condition or disability that could interfere with the assessment of safety or efficacy in this study or compromise the safety of the subject. History of hypersensitivity to serlopitant or any of its components. Currently pregnant or breastfeeding or planning to become pregnant during the study. Planned or anticipated major surgical procedure or other activity that would interfere with the subject's ability to comply with protocol-mandated assessments during participation in the study.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5 mg Serlopitant Tablets<br> | Drug: 5mg Serlopitant Tablets<br>* Serlopitant Tablets<br>* Other names: VPD-737;|
| Placebo Comparator: Matching Placebo Tablets<br> | Drug: Placebo Tablets<br>* Placebo Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Subjects With Worst-Itch Numeric Rating Scale 4-point Responder at Week 10 | During the study, Worst Itch Numeric Rating Scale (WI-NRS) assessments were reported by the subject via eDiary once daily from screening/mid-screening visit through the follow-up visit. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity and subjects were asked to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity. Subjects were considered responders if they had at least a 4-point reduction from baseline in weekly average WI-NRS at Week 10. | At Week 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Subjects With WI-NRS 4-point Responder at Week 4 | During the study, WI-NRS assessments were reported by the subject via eDiary once daily from screening/mid-screening visit through the follow-up visit. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity and subjects were asked to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity. | At Week 4 | 
| Percent of Subjects With WI-NRS 4-point Responder at Week 2 | During the study, WI-NRS assessments were reported by the subject via eDiary once daily from screening/mid-screening visit through the follow-up visit. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity and subjects were asked to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity. | At Week 2 | 
| Change From Baseline in WI-NRS at Weeks 2, 4, 6, and 10 | During the study, WI-NRS assessments were reported by the subject via eDiary once daily from screening/mid-screening visit through the follow-up visit. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity and subjects were asked to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity. | At Weeks 2, 4, 6, and 10 | 
| Percent of Subjects With WI-NRS 3-point Responder at Weeks 2, 4, and 10 | During the study, WI-NRS assessments were reported by the subject via eDiary once daily from screening/mid-screening visit through the follow-up visit. The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity and subjects were asked to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity. For the 3-point responder rate, subjects were considered responders if they had at least a 3-point reduction between baseline and the corresponding week. | At Weeks 2, 4, and 10 | 
| Change From Baseline in Investigator's Global Assessment of Prurigo Nodularis Activity (IGA PN-A) to Weeks 2, 4, and 10 | The IGA PN-A is an instrument used to assess the overall activity of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 (clear) to 4 (severe). Higher scores indicate severe prurigo nodularis. | At Weeks 2, 4, and 10 | 
| Change From Baseline in Investigator's Global Assessment of PN Stage (IGA PN-S) to Weeks 2, 4, and 10 | The IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 (clear) to 4 (severe). Higher scores indicate severe prurigo nodularis. | At Weeks 2, 4, and 10 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 10 | Dermatology Life Quality Index (DLQI) is a dermatology specific quality of life (QoL) instrument designed to assess the impact of the skin disease on a subject's QoL over the prior week. It is a ten item questionnaire that assesses overall QoL and six aspects that may affect QoL (symptoms and feelings, daily activities, leisure, work or school performance, personal relationships, and treatment). The DLQI questions are rated by the subject as 0 (not at all) to 3 (very much). Scores range from 0 to 30 with higher scores indicating poor QoL. | At Week 10 | 
| Change From Baseline in DLQI Question 1 to Week 10 | DLQI is a dermatology specific QoL instrument designed to assess the impact of the skin disease on a subject's QoL over the prior week. It is a ten item questionnaire that assesses overall QoL and six aspects that may affect QoL (symptoms and feelings, daily activities, leisure, work or school performance, personal relationships, and treatment) The DLQI question 1 is to measure how itchy, sore, painful or stinging the subject's skin had been. It is rated by the subject as 0 (not at all) to 3 (very much). Scores range from 0 to 30 with higher scores indicating poor QoL. | At Week 10 | 
| Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events (SAEs) | Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. Severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. During the period between informed consent and first study drug dose, only SAEs caused by a protocol-mandated intervention were collected. | 35 days (+3 days) after Week 10 or Early Treatment Discontinuation |