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

• Sponsor: Vyne Therapeutics Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03677401
• Collaborator: (none)
• Enrollment: 295
• Locations: 40
• Arms: 2
• Actual Duration (Months): 17.3
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Pruritus; Prurigo Nodularis	Drug: 5mg Serlopitant Tablets; Drug: Placebo Tablets	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 295 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Aug 29, 2018
• Actual Primary Completion Date: Jan 9, 2020
• Actual Study Completion Date: Feb 6, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Percent of Participants With Worst Itch Numeric Rating Scale (WI-NRS) 4-point Responder Rate at Week 10 [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).

Secondary Outcome Measures

1. Percent of Participants With WI-NRS 4-point Responder Rate at Week 4 [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).

2. Percent of Participants With WI-NRS 4-point Responder Rate at Week 2 [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).

3. Change From Baseline in WI-NRS at Weeks 2, 4, 6, and 10 [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.

4. Percent of Participants With WI-NRS 3-point Responder at Weeks 2, 4, and 10 [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).

5. Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 10 [At 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.).

6. Change From Baseline in DLQI Question 1 to Week 10 [At 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.).

7. Change From Baseline in Investigator's Global Assessment of Prurigo Nodularis Stage (IGA PN-S) to Weeks 2, 4, and 10 [At 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.

8. Change From Baseline in Investigator's Global Assessment of Prurigo Nodularis Activity (IGA PN-A) to Weeks 2, 4, and 10 [At 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.

9. Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events (SAEs) [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]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

4. Other neurokinin-1 receptor antagonists (e.g., aprepitant, fosaprepitant, rolapitant).

5. Systemic or topical immunosuppressive/immunomodulatory therapies.

6. Systemic therapies with recognized anti-pruritic properties.

7. Strong cytochrome-P 3A4 inhibitors.

8. Use of an indoor tanning facility, or natural sun exposure resulting in significant tanning or sunburn.

9. Treatment with topical anti-pruritic therapies within 2 weeks.

10. Treatment with biologic therapies within 8 weeks or 5 half-lives, whichever is longer.

11. Treatment with any investigational therapy within 4 weeks (8 weeks for investigational biologic therapies) or 5 half-lives, whichever is longer.

12. Serum creatinine, total bilirubin, alanine aminotransferase or aspartate aminotransferase > 2.5 times the upper limit of normal during screening.

13. Untreated or inadequately treated thyroid adrenal, or pituitary nodules or disease, or history of thyroid malignancy.

14. Malignancy within 5 years prior to enrollment (exception for non-melanoma cutaneous malignancies).

15. 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.

16. Documented history of parasitic infection, including skin parasites such as scabies, within 8 weeks.

17. 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.

18. History of hypersensitivity to serlopitant or any of its components.

19. Currently pregnant or breastfeeding or planning to become pregnant during the study.

20. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Study Site 649	Graz		Austria	8036
2	Study Site 648	Linz		Austria	4020
3	Study Site 650	Vienna		Austria	1130
4	Study Site 623	Bad Bentheim		Germany	48455
5	Study Site 607	Berlin		Germany	10117
6	Study Site 641	Berlin		Germany	10783
7	Study Site 600	Bielefeld		Germany	33647
8	Study Site 617	Bochum		Germany	44793
9	Study Site 608	Bonn		Germany	53127
10	Study Site 642	Buxtehude		Germany	21614
11	Study Site 606	Dresden		Germany	01307
12	Study Site 621	Erlangen		Germany	91054
13	Study Site 602	Frankfurt am main		Germany	60590
14	Study Site 639	Hamburg		Germany	22391
15	Study Site 605	Heidelberg		Germany	69115
16	Study Site 611	Leipzig		Germany	04103
17	Study Site 620	Mahlow		Germany	15831
18	Study Site 614	Mainz		Germany	55131
19	Study Site 601	Münster		Germany	48149
20	Study Site 618	Osnabrück		Germany	49074
21	Study Site 640	Potsdam		Germany	14467
22	Study Site 615	Selters		Germany	56242
23	Study Site 643	Stuttgart		Germany	70178
24	Study Site 636	Bydgoszcz		Poland	85-065
25	Study Site 628	Iwonicz-Zdrój		Poland	38-440
26	Study Site 633	Kraków		Poland	30-033
27	Study Site 624	Kraków		Poland	31-070
28	Study Site 635	Kraków		Poland	31-209
29	Study Site 631	Olsztyn		Poland	10-900
30	Study Site 625	Osielsko		Poland	86-031
31	Study Site 645	Poznań		Poland	60-214
32	Study Site 644	Poznań		Poland	60-848
33	Study Site 634	Rzeszów		Poland	35-055
34	Study Site 638	Szczecin		Poland	70-332
35	Study Site 632	Toruń		Poland	87-100
36	Study Site 627	Warszawa		Poland	02-758
37	Study Site 637	Wrocław		Poland	50-566
38	Study Site 630	Wrocław		Poland	53-301
39	Study Site 647	Wrocław		Poland	53-658
40	Study Site 629	Łódź		Poland	90-436

Sponsors and Collaborators

• 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 Documents (Full-Text)

• Study Protocol - Dec 16, 2019
• Statistical Analysis Plan - Dec 16, 2019

More Information

Publications

None provided.

• Responsible Party: Vyne Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT03677401
• Other Study ID Numbers: MTI-106; 2017-004210-25
• First Posted: Sep 19, 2018
• Last Update Posted: May 20, 2021
• Last Verified: May 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Pruritus; Prurigo; Neurodermatitis; Serlopitant

Study Results

Participant Flow

Recruitment Details	The study was conducted at 40 sites in US from 29 August 2018 to 06 February 2020. All psrticipants who met the study entry criteria were randomized in a 1:1 ratio to receive daily oral doses of serlopitant 5 mg or placebo.
Pre-assignment Detail	During the screening period (4 weeks), all participants were evaluated for eligibility and chronic pruritic conditions frequently associated with Prurigo Nodularis. Participants were to complete an electronic diary (eDiary) at the Screening visit.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	Randomized participants received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.	Randomized participants received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.
Period Title: Overall Study
STARTED	148	147
COMPLETED	138	129
NOT COMPLETED	10	18

Baseline Characteristics

Arm/Group Title	Placebo	Serlopitant 5 mg	Total
Arm/Group Description	Randomized participants received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.	Randomized participants received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.	Total of all reporting groups
Overall Participants	148	147	295
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.5 (12.97)	57.5 (15.33)	58.0 (14.18)
Sex: Female, Male (Count of Participants)
Female	94 63.5%	98 66.7%	192 65.1%
Male	54 36.5%	49 33.3%	103 34.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 0.7%	2 1.4%	3 1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 1.4%	0 0%	2 0.7%
White	145 98%	145 98.6%	290 98.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percent of Participants With Worst Itch Numeric Rating Scale (WI-NRS) 4-point Responder Rate at Week 10
Description	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).
Time Frame	At Week 10

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population: included all randomized participants who were dispensed study drug.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	Randomized participants received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.	Randomized participants received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.
Measure Participants	148	147
Success	18.95 12.8%	25.90 17.6%
Failure	81.05 54.8%	74.10 50.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 10
	Type of Statistical Test	Superiority
	Comments	P-value from a Cochran-Mantel- Haenszel (CMH) test stratified by Baseline WI-NRS used for randomization stratification. Value has been adjusted for multiple imputation.
Statistical Test of Hypothesis	p-Value	0.158
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

Title	Percent of Participants With WI-NRS 4-point Responder Rate at Week 4
Description	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).
Time Frame	At Week 4

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population: included all randomized participants who were dispensed study drug.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	Randomized participants received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.	Randomized participants received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.
Measure Participants	148	147
Success	11.49 7.8%	12.63 8.6%
Failure	88.51 59.8%	87.37 59.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 4
	Type of Statistical Test	Superiority
	Comments	P-value from a CMH test stratified by Baseline WI-NRS used for randomization stratification. Value has been adjusted for multiple imputation.
Statistical Test of Hypothesis	p-Value	0.750
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

3. Secondary Outcome

Title	Percent of Participants With WI-NRS 4-point Responder Rate at Week 2
Description	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).
Time Frame	At Week 2

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population: included all randomized participants who were dispensed study drug.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	Randomized participants received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.	Randomized participants received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.
Measure Participants	148	147
Success	6.76 4.6%	5.55 3.8%
Failure	93.24 63%	94.45 64.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 2
	Type of Statistical Test	Superiority
	Comments	P-value from a CMH test stratified by Baseline WI-NRS used for randomization stratification. Value has been adjusted for multiple imputation
Statistical Test of Hypothesis	p-Value	0.674
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

4. Secondary Outcome

Title	Change From Baseline in WI-NRS at Weeks 2, 4, 6, and 10
Description	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.
Time Frame	At Weeks 2, 4, 6, and 10

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population: included all randomized participants who were dispensed study drug.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	Randomized participants received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.	Randomized participants received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.
Measure Participants	148	147
Change from Baseline at Week 2	-0.94 (1.470)	-1.25 (1.496)
Change from Baseline at Week 4	-1.42 (1.908)	-1.60 (1.955)
Change from Baseline at Week 6	-1.61 (2.105)	-1.93 (2.182)
Change from Baseline at Week 10	-1.86 (2.334)	-2.24 (2.543)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 2
	Type of Statistical Test	Superiority
	Comments	P-values, least squares means (LS Mean) and standard deviations (LS SD) from an analysis of covariance (ANCOVA) with treatment group and stratification factor as fixed effects, and baseline value as a covariate.
Statistical Test of Hypothesis	p-Value	0.060
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.401
	Comments	P-values, LS Mean and LS SD from ANCOVA with treatment group and stratification factor as fixed effects, and baseline value as a covariate.
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 6
	Type of Statistical Test	Superiority
	Comments	P-values, LS Mean and LS SD from ANCOVA with treatment group and stratification factor as fixed effects, and baseline value as a covariate.
Statistical Test of Hypothesis	p-Value	0.185
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 10
	Type of Statistical Test	Superiority
	Comments	P-values, LS Mean and LS SD from ANCOVA with treatment group and stratification factor as fixed effects, and baseline value as a covariate.
Statistical Test of Hypothesis	p-Value	0.164
	Comments
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	Percent of Participants With WI-NRS 3-point Responder at Weeks 2, 4, and 10
Description	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).
Time Frame	At Weeks 2, 4, and 10

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population: included all randomized participants who were dispensed study drug.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	Randomized participants received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.	Randomized participants received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.
Measure Participants	148	147
Percentage of responders at Week 2	8.11 5.5%	11.89 8.1%
Percentage of responders at Week 4	18.24 12.3%	20.03 13.6%
Percentage of responders at Week 10	25.65 17.3%	37.58 25.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.283
	Comments	P-value from a CMH test stratified by Baseline WI-NRS used for randomization stratification. Value has been adjusted for multiple imputation.
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.701
	Comments	P-value from a CMH test stratified by Baseline WI-NRS used for randomization stratification. Value has been adjusted for multiple imputation.
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 10
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.033
	Comments	P-value from a CMH test stratified by Baseline WI-NRS used for randomization stratification. Value has been adjusted for multiple imputation.
	Method	Cochran-Mantel-Haenszel
	Comments

6. Secondary Outcome

Title	Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 10
Description	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.).
Time Frame	At Week 10

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population: included all randomized participants who were dispensed study drug.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	Randomized participants received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.	Randomized participants received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.
Measure Participants	148	147
Mean (Standard Deviation) [Score on a scale]	-4.4 (5.07)	-4.5 (5.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 10
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.797
	Comments	P-values, LS mean and SD from ANCOVA with treatment group and stratification factor as fixed effects, and baseline value as a covariate.
	Method	ANCOVA
	Comments

7. Secondary Outcome

Title	Change From Baseline in DLQI Question 1 to Week 10
Description	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.).
Time Frame	At Week 10

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population: included all randomized participants who were dispensed study drug.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	Randomized participants received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.	Randomized participants received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.
Measure Participants	148	147
Mean (Standard Deviation) [Score on a scale]	-0.6 (0.75)	-0.6 (0.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 10
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.845
	Comments	P-values, LS mean and SD from ANCOVA with treatment group and stratification factor as fixed effects, and baseline value as a covariate.
	Method	ANCOVA
	Comments

8. Secondary Outcome

Title	Change From Baseline in Investigator's Global Assessment of Prurigo Nodularis Stage (IGA PN-S) to Weeks 2, 4, and 10
Description	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.
Time Frame	At Weeks 2, 4 and 10

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population: included all randomized participants who were dispensed study drug.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	Randomized participants received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.	Randomized participants received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.
Measure Participants	148	147
Change from Baseline at Week 2	-0.2 (0.43)	-0.2 (0.43)
Change from Baseline at Week 4	-0.4 (0.64)	-0.3 (0.64)
Change from Baseline at Week 10	-0.5 (0.77)	-0.5 (0.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.385
	Comments	P-values, LS mean and SD from ANCOVA with treatment group and stratification factor as fixed effects, and baseline value as a covariate.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.786
	Comments	P-values, LS mean and SD from ANCOVA with treatment group and stratification factor as fixed effects, and baseline value as a covariate.
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 10
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.502
	Comments	P-values, LS mean and SD from ANCOVA with treatment group and stratification factor as fixed effects, and baseline value as a covariate.
	Method	ANCOVA
	Comments

9. Secondary Outcome

Title	Change From Baseline in Investigator's Global Assessment of Prurigo Nodularis Activity (IGA PN-A) to Weeks 2, 4, and 10
Description	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.
Time Frame	At Weeks 2, 4, and 10

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population: included all randomized participants who were dispensed study drug.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	Randomized participants received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.	Randomized participants received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.
Measure Participants	148	147
Change from Baseline at Week 2	-0.2 (0.49)	-0.3 (0.49)
Change from Baseline at Week 4	-0.5 (0.68)	-0.5 (0.68)
Change from Baseline at Week 10	-0.7 (0.91)	-0.7 (0.92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.197
	Comments	P-values, LS mean and SD from ANCOVA with treatment group and stratification factor as fixed effects, and baseline value as a covariate.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.694
	Comments	P-values, LS mean and SD from ANCOVA with treatment group and stratification factor as fixed effects, and baseline value as a covariate.
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Serlopitant 5 mg
	Comments	At Week 10
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.916
	Comments	P-values, LS mean and SD from ANCOVA with treatment group and stratification factor as fixed effects, and baseline value as a covariate.
	Method	ANCOVA
	Comments

10. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events (SAEs)
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Safety population: included all treated participants with at least one post-baseline assessment or a reported TEAE.

Arm/Group Title	Placebo	Serlopitant 5 mg
Arm/Group Description	Randomized participants received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.	Randomized participants received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.
Measure Participants	148	147
Participants with any TEAE	87 58.8%	84 57.1%
Participants with any related TEAE	24 16.2%	30 20.4%
Participants with any serious TEAE	2 1.4%	5 3.4%
Participants with any related serious TEAE	0 0%	0 0%
Participants who Died	0 0%	0 0%
Participants who discontinued study drug	4 2.7%	13 8.8%

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	Adverse events (AEs) and serious adverse events (SAEs) were recorded from the first study drug administration through the follow-up visit. After informed consent was signed, but prior to initiation of study drug, only SAEs considered by the investigator to be caused by a protocol mandated intervention were collected.
Arm/Group Title	Placebo		Serlopitant 5 mg
Arm/Group Description	Randomized participants received daily oral doses of placebo following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.		Randomized participants received daily oral doses of serlopitant 5 mg following an initial 3-tablet loading dose on Day 1. Starting on Day 2, participants took 1 tablet per day until the completion of the 10-week treatment period.
All Cause Mortality
	Placebo		Serlopitant 5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/148 (0%)		1/147 (0.7%)
Serious Adverse Events
	Placebo		Serlopitant 5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/148 (1.4%)		5/147 (3.4%)
Cardiac disorders
Coronary artery disease	0/148 (0%)		1/147 (0.7%)
Injury, poisoning and procedural complications
Wound	0/148 (0%)		1/147 (0.7%)
Investigations
Hepatic enzyme increased	0/148 (0%)		1/147 (0.7%)
Metabolism and nutrition disorders
Type 2 diabetes mellitus	1/148 (0.7%)		0/147 (0%)
Musculoskeletal and connective tissue disorders
Crystal arthropathy	0/148 (0%)		1/147 (0.7%)
Intervertebral disc protrusion	0/148 (0%)		1/147 (0.7%)
Rhabdomyolysis	1/148 (0.7%)		0/147 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma	0/148 (0%)		1/147 (0.7%)
Vascular disorders
Hypertensive crisis	1/148 (0.7%)		0/147 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Serlopitant 5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/148 (22.3%)		31/147 (21.1%)
General disorders
Fatigue	6/148 (4.1%)		7/147 (4.8%)
Infections and infestations
Nasopharyngitis	22/148 (14.9%)		15/147 (10.2%)
Nervous system disorders
Headache	5/148 (3.4%)		9/147 (6.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.