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

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

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

Study Overview

• Status: Completed
• Conditions: Pruritus; Prurigo Nodularis
• Intervention / Treatment: Drug: 5mg Serlopitant Tablets; Drug: Placebo Tablets

• Study Type: Interventional
• Enrollment (Actual): 295
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Study Site 649
  • Linz, Austria, 4020
    • Study Site 648
  • Vienna, Austria, 1130
    • Study Site 650
• Germany
  • Bad Bentheim, Germany, 48455
    • Study Site 623
  • Berlin, Germany, 10117
    • Study Site 607
  • Berlin, Germany, 10783
    • Study Site 641
  • Bielefeld, Germany, 33647
    • Study Site 600
  • Bochum, Germany, 44793
    • Study Site 617
  • Bonn, Germany, 53127
    • Study Site 608
  • Buxtehude, Germany, 21614
    • Study Site 642
  • Dresden, Germany, 01307
    • Study Site 606
  • Erlangen, Germany, 91054
    • Study Site 621
  • Frankfurt am main, Germany, 60590
    • Study Site 602
  • Hamburg, Germany, 22391
    • Study Site 639
  • Heidelberg, Germany, 69115
    • Study Site 605
  • Leipzig, Germany, 04103
    • Study Site 611
  • Mahlow, Germany, 15831
    • Study Site 620
  • Mainz, Germany, 55131
    • Study Site 614
  • Münster, Germany, 48149
    • Study Site 601
  • Osnabrück, Germany, 49074
    • Study Site 618
  • Potsdam, Germany, 14467
    • Study Site 640
  • Selters, Germany, 56242
    • Study Site 615
  • Stuttgart, Germany, 70178
    • Study Site 643
• Poland
  • Bydgoszcz, Poland, 85-065
    • Study Site 636
  • Iwonicz-Zdrój, Poland, 38-440
    • Study Site 628
  • Kraków, Poland, 30-033
    • Study Site 633
  • Kraków, Poland, 31-070
    • Study Site 624
  • Kraków, Poland, 31-209
    • Study Site 635
  • Olsztyn, Poland, 10-900
    • Study Site 631
  • Osielsko, Poland, 86-031
    • Study Site 625
  • Poznań, Poland, 60-214
    • Study Site 645
  • Poznań, Poland, 60-848
    • Study Site 644
  • Rzeszów, Poland, 35-055
    • Study Site 634
  • Szczecin, Poland, 70-332
    • Study Site 638
  • Toruń, Poland, 87-100
    • Study Site 632
  • Warszawa, Poland, 02-758
    • Study Site 627
  • Wrocław, Poland, 50-566
    • Study Site 637
  • Wrocław, Poland, 53-301
    • Study Site 630
  • Wrocław, Poland, 53-658
    • Study Site 647
  • Łódź, Poland, 90-436
    • Study Site 629

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria (Subjects must meet the following criteria to be randomized into the study:

1. Male or female, age 18 years or older at consent.
2. Prurigo nodularis (PN), with at least ten nodules on at least two different body surface areas.
3. 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.
4. 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.
5. Female subjects of childbearing potential must be willing to practice highly effective contraception until 5 weeks after last dose of study drug.
6. Willing and able to complete daily eDiary entries within a consistent timeframe for the duration of the study.
7. 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):

1. Prior treatment with serlopitant.
2. 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).

3. Treatment with any of the following therapies within 4 weeks.

   1. Other neurokinin-1 receptor antagonists (e.g., aprepitant, fosaprepitant, rolapitant).
   2. Systemic or topical immunosuppressive/immunomodulatory therapies.
   3. Systemic therapies with recognized anti-pruritic properties.
   4. Strong cytochrome-P 3A4 inhibitors.
   5. Use of an indoor tanning facility, or natural sun exposure resulting in significant tanning or sunburn.
4. Treatment with topical anti-pruritic therapies within 2 weeks.
5. Treatment with biologic therapies within 8 weeks or 5 half-lives, whichever is longer.
6. Treatment with any investigational therapy within 4 weeks (8 weeks for investigational biologic therapies) or 5 half-lives, whichever is longer.
7. Serum creatinine, total bilirubin, alanine aminotransferase or aspartate aminotransferase > 2.5 times the upper limit of normal during screening.
8. Untreated or inadequately treated thyroid adrenal, or pituitary nodules or disease, or history of thyroid malignancy.
9. Malignancy within 5 years prior to enrollment (exception for non-melanoma cutaneous malignancies).
10. 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.
11. Documented history of parasitic infection, including skin parasites such as scabies, within 8 weeks.
12. 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.
13. History of hypersensitivity to serlopitant or any of its components.
14. Currently pregnant or breastfeeding or planning to become pregnant during the study.
15. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5 mg Serlopitant Tablets	Drug: 5mg Serlopitant Tablets; Serlopitant Tablets; Other Names: VPD-737
Placebo Comparator: Matching Placebo Tablets	Drug: Placebo Tablets; Placebo Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants With Worst Itch Numeric Rating Scale (WI-NRS) 4-point Responder Rate at Week 10	During the study, WI-NRS assessments were reported by the participant 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 participants 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. A participant was a 4-point responder if their change from baseline is ≤ -4 (i.e. a decrease of at least 4).	At Week 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants With WI-NRS 4-point Responder Rate at Week 4	During the study, WI-NRS assessments were reported by the participant 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 participants 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. A participant was a 4-point responder if their change from baseline is ≤ -4 (i.e. a decrease of at least 4).	At Week 4
Percent of Participants With WI-NRS 4-point Responder Rate at Week 2	During the study, WI-NRS assessments were reported by the participant 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 participants 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. A participant was a 4-point responder if their change from baseline is ≤ -4 (i.e. a decrease of at least 4).	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 participant 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 participants 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 Participants With WI-NRS 3-point Responder at Weeks 2, 4, and 10	During the study, WI-NRS assessments were reported by the participant 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 participants 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. A participant was a 3-point responder if their change from baseline is ≤ -3 (i.e. a decrease of at least 3).	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 participant'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 participant 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	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 participant'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 participant 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 Investigator's Global Assessment of Prurigo Nodularis 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 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
Number of Participants 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.	From screening until the Follow-up (F/U) visit which occurred 35 days (+ 7 days) after the Week 10 visit or the last dose of study drug for participants who discontinued study drug early

Collaborators and Investigators

• Sponsor: Vyne Therapeutics Inc.
• Investigators: Principal Investigator: Sonja Stander, MD, Universitätsklinikum Münster Klinik für Hautkrankheiten Zentrale Studienkoordination für innovative Dermaologie (ZID); Principal Investigator: Jacek Szepietowski, MD, Ph.D, Lukasz Matusiak 4health; Principal Investigator: Franz Josef Legat, MD, Medizinische Universität Graz

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2018
• Primary Completion (Actual): January 9, 2020
• Study Completion (Actual): February 6, 2020

Study Registration Dates

• First Submitted: September 17, 2018
• First Submitted That Met QC Criteria: September 17, 2018
• First Posted (Actual): September 19, 2018

Study Record Updates

• Last Update Posted (Actual): May 20, 2021
• Last Update Submitted That Met QC Criteria: May 18, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Manifestations; Dermatitis; Skin Diseases, Eczematous; Pruritus; Prurigo; Neurodermatitis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurokinin-1 Receptor Antagonists; Serlopitant
• Other Study ID Numbers: MTI-106; 2017-004210-25 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No