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: NCT03546816
• Collaborator: (none)
• Enrollment: 285
• Locations: 49
• Arms: 2
• Actual Duration (Months): 21.5
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.3

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: 285 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: May 2, 2018
• Actual Primary Completion Date: Jan 14, 2020
• Actual Study Completion Date: Feb 14, 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 Subjects With Worst-Itch Numeric Rating Scale 4-point Responder at Week 10 [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.

Secondary Outcome Measures

1. Percent of Subjects With WI-NRS 4-point Responder at Week 4 [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.

2. Percent of Subjects With WI-NRS 4-point Responder at Week 2 [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.

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 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.

4. Percent of Subjects 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 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.

5. 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.

6. Change From Baseline in Investigator's Global Assessment of PN 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.

7. 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 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.

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

9. Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events (SAEs) [35 days (+3 days) after Week 10 or Early Treatment Discontinuation]

   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 504	Birmingham	Alabama	United States	35233
2	Study Site 533	Rogers	Arkansas	United States	72758
3	Study Site 204	Fremont	California	United States	94538
4	Study Site 383	North Hollywood	California	United States	91606
5	Study Site 356	San Diego	California	United States	92108
6	Study Site 514	Santa Ana	California	United States	92701
7	Study Site 501	Aventura	Florida	United States	33180
8	Study Site 210	Coral Gables	Florida	United States	33134
9	Study Site 534	Fort Lauderdale	Florida	United States	33316
10	Study Site 531	Miami	Florida	United States	33155
11	Study Site 530	Miami	Florida	United States	33165
12	Study Site 222	North Miami Beach	Florida	United States	33162
13	Study Site 510	Newnan	Georgia	United States	30263
14	Study Site 388	Skokie	Illinois	United States	60077
15	Study Site 228	Louisville	Kentucky	United States	40202
16	Study Site 527	New Orleans	Louisiana	United States	70115
17	Study Site 525	Glenn Dale	Maryland	United States	20769
18	Study Site 379	Boston	Massachusetts	United States	02114
19	Study Site 506	Ann Arbor	Michigan	United States	48103
20	Study Site 515	Detroit	Michigan	United States	48202
21	Study Site 371	Saint Joseph	Missouri	United States	64506
22	Study Site 528	Saint Louis	Missouri	United States	63110
23	Study Site 227	Omaha	Nebraska	United States	68144
24	Study Site 526	Henderson	Nevada	United States	89052
25	Study Site 201	East Windsor	New Jersey	United States	08520
26	Study Site 529	Verona	New Jersey	United States	07044-2946
27	Study Site 507	Brooklyn	New York	United States	11203
28	Study Site 508	Buffalo	New York	United States	14221
29	Study Site 500	New York	New York	United States	10025
30	Study Site 517	New York	New York	United States	10075
31	Study Site 341	High Point	North Carolina	United States	27262
32	Study Site 516	Bexley	Ohio	United States	43209
33	Study Site 509	Cleveland	Ohio	United States	44106
34	Study Site 524	Dublin	Ohio	United States	43016
35	Study Site 112	Tulsa	Oklahoma	United States	74136
36	Study Site 523	Philadelphia	Pennsylvania	United States	19104
37	Study Site 522	Pittsburgh	Pennsylvania	United States	15213
38	Study Site 345	Johnston	Rhode Island	United States	02919
39	Study Site 511	Knoxville	Tennessee	United States	37317
40	Study Site 805	Nashville	Tennessee	United States	37215
41	Study Site 365	Austin	Texas	United States	78745
42	Study Site 520	Bellaire	Texas	United States	77401
43	Study Site 502	Dallas	Texas	United States	75231
44	Study Site 224	Houston	Texas	United States	77004
45	Study Site 359	Pflugerville	Texas	United States	78660
46	Study Site 361	San Antonio	Texas	United States	78213
47	Study Site 226	Webster	Texas	United States	77598
48	Study Site 806	Spokane	Washington	United States	99202
49	Study Site 532	Morgantown	West Virginia	United States	26505

Sponsors and Collaborators

• Vyne Therapeutics Inc.

Investigators

None specified.

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: NCT03546816
• Other Study ID Numbers: MTI-105
• First Posted: Jun 6, 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 49 sites in United States from 02 May 2018 to 14 February 2020. All subjects who met the study entry criteria were randomized in a 1:1 ratio to receive once-daily oral doses of serlopitant 5 mg or placebo for 10 weeks.
Pre-assignment Detail	During the screening period (2-4 weeks), all subjects were evaluated for eligibility and assessed for conditions associated with chronic pruritus. Subjects were to complete an electronic diary (eDiary) during screening visit.

Arm/Group Title	Serlopitant 5 mg	Placebo
Arm/Group Description	Randomized subjects received serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Period Title: Overall Study
STARTED	142	143
COMPLETED	121	124
NOT COMPLETED	21	19

Baseline Characteristics

Arm/Group Title	Serlopitant 5 mg	Placebo	Total
Arm/Group Description	Randomized subjects received serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Total of all reporting groups
Overall Participants	142	143	285
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58.7 (13.54)	56.0 (12.99)	57.4 (13.30)
Sex: Female, Male (Count of Participants)
Female	92 64.8%	89 62.2%	181 63.5%
Male	47 33.1%	52 36.4%	99 34.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.7%	0 0%	1 0.4%
Asian	6 4.2%	11 7.7%	17 6%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.7%	1 0.4%
Black or African American	27 19%	33 23.1%	60 21.1%
White	102 71.8%	91 63.6%	193 67.7%
More than one race	3 2.1%	5 3.5%	8 2.8%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percent of Subjects With Worst-Itch Numeric Rating Scale 4-point Responder at Week 10
Description	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.
Time Frame	At Week 10

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Serlopitant 5 mg	Placebo
Arm/Group Description	Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Measure Participants	142	142
Number [Percentage of subjects]	26.45	20.31

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Serlopitant 5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.229
	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.
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Serlopitant 5 mg	Placebo
Arm/Group Description	Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day on an outpatient basis.	Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day on an outpatient basis.
Measure Participants	142	142
Number [Percentage of subjects]	17.66	7.80

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Serlopitant 5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	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

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Serlopitant 5 mg	Placebo
Arm/Group Description	Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Measure Participants	142	142
Number [Percentage of subjects]	8.45	4.93

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Serlopitant 5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.236
	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

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 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.
Time Frame	At Weeks 2, 4, 6, and 10

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Serlopitant 5 mg	Placebo
Arm/Group Description	Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Measure Participants	142	142
Change from Baseline at Week 2	-1.30 (1.725)	-0.96 (1.740)
Change from Baseline at Week 4	-1.82 (2.226)	-1.32 (2.248)
Change from Baseline at Week 6	-2.13 (2.436)	-1.65 (2.460)
Change from Baseline at Week 10	-2.47 (2.633)	-2.06 (2.612)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Serlopitant 5 mg, Placebo
	Comments	At Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.083
	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.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Serlopitant 5 mg, Placebo
	Comments	At Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.049
	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	Serlopitant 5 mg, Placebo
	Comments	At Week 6
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.081
	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 4

Statistical Analysis Overview	Comparison Group Selection	Serlopitant 5 mg, Placebo
	Comments	At Week 10
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.157
	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

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Serlopitant 5 mg	Placebo
Arm/Group Description	Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Measure Participants	142	142
Percentage of responders at Week 2	14.79	9.27
Percentage of responders at Week 4	23.32	14.31
Percentage of responders at Week 10	35.58	27.83

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Serlopitant 5 mg, Placebo
	Comments	At Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.151
	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	Serlopitant 5 mg, Placebo
	Comments	At Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.052
	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	Serlopitant 5 mg, Placebo
	Comments	At Week 10
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.175
	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 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 subjects who were dispensed study drug.

Arm/Group Title	Serlopitant 5 mg	Placebo
Arm/Group Description	Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Measure Participants	142	142
Change from Baseline at Week 2	-0.3 (0.71)	-0.3 (0.71)
Change from Baseline at Week 4	-0.6 (0.81)	-0.4 (0.81)
Change from Baseline at Week 10	-0.7 (0.99)	-0.6 (0.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Serlopitant 5 mg, Placebo
	Comments	At Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.475
	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	Serlopitant 5 mg, Placebo
	Comments	At Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.020
	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	Serlopitant 5 mg, Placebo
	Comments	At Week 10
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.492
	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 Investigator's Global Assessment of PN 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 subjects who were dispensed study drug.

Arm/Group Title	Serlopitant 5 mg	Placebo
Arm/Group Description	Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Measure Participants	142	142
Change from Baseline to Week 2	-0.2 (0.52)	-0.1 (0.52)
Change from Baseline to Week 4	-0.4 (0.71)	-0.3 (0.71)
Change from Baseline to Week 10	-0.5 (0.86)	-0.4 (0.86)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Serlopitant 5 mg, Placebo
	Comments	At Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.175
	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	Serlopitant 5 mg, Placebo
	Comments	At Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.169
	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	Serlopitant 5 mg, Placebo
	Comments	At Week 10
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.516
	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 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 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.
Time Frame	At Week 10

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Serlopitant 5 mg	Placebo
Arm/Group Description	Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Measure Participants	142	142
Mean (Standard Deviation) [Score on a scale]	-4.1 (5.20)	-4.3 (5.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Serlopitant 5 mg, Placebo
	Comments	At Week 10
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.814
	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 DLQI Question 1 to Week 10
Description	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.
Time Frame	At Week 10

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Serlopitant 5 mg	Placebo
Arm/Group Description	Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Measure Participants	142	142
Mean (Standard Deviation) [Score on a scale]	-0.8 (0.80)	-0.6 (0.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Serlopitant 5 mg, Placebo
	Comments	At Week 10
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.113
	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 Subjects 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	35 days (+3 days) after Week 10 or Early Treatment Discontinuation

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Serlopitant 5 mg	Placebo
Arm/Group Description	Randomized subjects received Serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.	Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
Measure Participants	139	141
Subjects with any TEAE	74 52.1%	64 44.8%
Subjects with any Related TEAE	20 14.1%	9 6.3%
Subjects with any Serious TEAE	6 4.2%	3 2.1%
Subjects with any Related Serious TEAE	0 0%	0 0%
Subjects who Died	0 0%	0 0%
Subjects who discontinued drug due to TEAE	5 3.5%	3 2.1%

Adverse Events

Time Frame	35 days (+3 days) after Week 10 or Early Treatment Discontinuation
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. 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.
Arm/Group Title	Serlopitant 5 mg		Placebo
Arm/Group Description	Randomized subjects received serlopitant 5 mg as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.		Randomized subjects received placebo as an initial loading dose (3 tablets orally) on Day 1, the first day of the treatment period. Thereafter, starting on Day 2, subjects were instructed to take 1 tablet orally per day.
All Cause Mortality
	Serlopitant 5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/139 (0%)		0/141 (0%)
Serious Adverse Events
	Serlopitant 5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/139 (4.3%)		3/141 (2.1%)
Gastrointestinal disorders
Haematochezia	1/139 (0.7%)		0/141 (0%)
Infections and infestations
Pneumonia	1/139 (0.7%)		0/141 (0%)
Abscess limb	0/139 (0%)		1/141 (0.7%)
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration	0/139 (0%)		1/141 (0.7%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/139 (0.7%)		0/141 (0%)
Psychiatric disorders
Schizoaffective disorder	1/139 (0.7%)		0/141 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/139 (0.7%)		0/141 (0%)
Acute respiratory failure	1/139 (0.7%)		0/141 (0%)
Surgical and medical procedures
Knee arthroplasty	0/139 (0%)		1/141 (0.7%)
Vascular disorders
Peripheral arterial occlusive disease	1/139 (0.7%)		0/141 (0%)
Other (Not Including Serious) Adverse Events
	Serlopitant 5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/141 (12.8%)		5/139 (3.6%)
Infections and infestations
Upper respiratory tract infection	10/141 (7.1%)		3/139 (2.2%)
Skin and subcutaneous tissue disorders
Pruritus	9/141 (6.4%)		2/139 (1.4%)

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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.