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

• Sponsor: Vyne Therapeutics Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03343639
• Collaborator: (none)
• Enrollment: 204
• Locations: 39
• Arms: 2
• Actual Duration (Months): 12.4
• Patients Per Site: 5.2
• 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 plaque psoriasis

Condition or Disease	Intervention/Treatment	Phase
Pruritus; Psoriasis	Drug: 5 mg Serlopitant Tablets; Drug: Matching Placebo Tablets	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 204 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 Plaque Psoriasis
• Actual Study Start Date: Nov 1, 2017
• Actual Primary Completion Date: Oct 23, 2018
• Actual Study Completion Date: Nov 12, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. WI-NRS 4-point Responder Rate at Week 8 [8 weeks]

   Worst Itch Numeric Rating Scale (WI-NRS). 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicate greater itch intensity. A 4-point responder is a subject who had at least a 4-point reduction in score between Baseline and Week 8.

Secondary Outcome Measures

1. WI-NRS 4-point Responder Rate at Week 4 [4 weeks]

   Worst Itch Numeric Rating Scale (WI-NRS). 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicate greater itch intensity. A 4-point responder is a subject who had at least a 4-point reduction in score between Baseline and Week 4.

2. Change in WI-NRS From Baseline to Day 7 [Change from baseline to day 7]

   Worst Itch Numeric Rating Scale (WI-NRS). 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicate greater itch intensity. The secondary outcome is the change in WI-NRS score at 7 days compared with Baseline.

3. Change in WI-NRS From Baseline to Day 3 [3 days]

   Worst Itch Numeric Rating Scale (WI-NRS). 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicate greater itch intensity. The secondary outcome is the change in WI-NRS score at 3 days compared with Baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female, age 18-80 years at consent.

2. Diagnosis of plaque psoriasis for at least 6 months prior to randomization.

1. Presence of plaque psoriasis in any anatomic location, covering ≤ 10% BSA in total, at the Screening and Baseline visits.

1. Pruritus of at least 4 weeks' duration prior to the initial Screening visit, and throughout the screening period prior to randomization.

2. Subjects must be willing to discontinue use of all psoriasis therapies other than the following, for the duration of the study: bland emollients (e.g., Cetaphil, Eucerin, Aquaphor) on any anatomic location; coal tar shampoos, limited to use on scalp.

3. WI-NRS initial screening score consistent with severe pruritus.

4. WI-NRS scores during the 2 weeks of screening consistent with sever pruritus.

5. All female subjects who are of childbearing potential must be willing to practice highly effective contraception (i.e., pregnancy prevention method with a failure rate of < 1% per year) from the time of the initial Screening visit until 2 weeks after last dose of study drug.

6. Weight ≥ 32 kg at the Screening and Baseline visits.

7. Willing and able to complete daily eDiary entries within a consistent timeframe for the duration of the study.

8. Subjects must have ≥ 80% eDiary completion rate during the two weeks of the screening period immediately prior to randomization.

Exclusion Criteria:

1. Prior treatment with serlopitant.

1. Prior treatment with other neurokinin-1 receptor (NK1-R) antagonists (e.g., aprepitant, fosaprepitant, rolapitant) is not allowed within 1 year prior to randomization.

1. Clinical worsening of psoriasis in the opinion of the investigator (e.g., increase in affected BSA or severity requiring use of systemic psoriasis therapies) within 12 weeks prior to randomization.

2. Predominance of non-plaque forms of psoriasis (e.g., guttate, drug-induced, pustular, erythrodermic).

3. Presence of any concurrent medical condition that provides a clearly defined etiology for pruritus other than psoriasis. These include but are not limited to urticaria, atopic dermatitis or other dermatologic conditions, hepatic or renal disease, psychogenic pruritus, drug reaction, untreated hyperthyroidism, and infection.

4. Treatment with systemic biologic therapies including but not limited to etanercept, infliximab, adalimumab, ustekinumab, secukinumab, or ixekizumab, within 6 months or 5 half-lives (whichever is longer) prior to randomization.

5. Treatment with systemic non-biologic psoriasis therapies, including but not limited to systemic corticosteroids, phosphodiesterase-4 inhibitors, Janus kinase inhibitors, cyclosporine, methotrexate, retinoids, hydroxyurea, mycophenolate mofetil, thioguanine, sirolimus, azathioprine, or fumaric acid derivatives, within 12 weeks prior to randomization.

6. Treatment with any of the following therapies within 4 weeks prior to randomization:

1. Any topical/local psoriasis therapies other than those permitted per inclusion #4, including but not limited to topical corticosteroids, vitamin D analogues, calcineurin inhibitors, phosphodiesterase-4 inhibitors, Janus kinase inhibitors, non-shampoo forms of coal tar, salicylates, retinoids, anthralin, or excimer laser.

2. Non-systemic corticosteroids that do not involve skin application (e.g., inhaled, intranasal, or intra-articular corticosteroids) will be permitted.

3. Phototherapy, with or without psoralen. c. Use of an indoor tanning facility, or sun exposure likely to result in sunburn.

4. Systemic therapies with recognized anti-pruritic properties including but not limited to H1 antihistamines, doxepin, mirtazapine, gabapentin, pregabalin, cannabinoids, and kappa opioid receptor agonists.

5. Any topical anti-pruritic therapies, including but not limited to H1 antihistamines, doxepin, capsaicin, or medicated emollients (e.g., menthol or pramoxine).

6. Strong CYP3A4 inhibitors.

1. Treatment with any investigational therapy within 4 weeks or 5 half-lives (whichever is longer) prior to randomization.

2. Serum creatinine, total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2x the upper limit of normal (ULN) during screening.

3. History of malignancy within 5 years prior to randomization, with the exception of completely treated and non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin.

4. Presence of any of the following conditions meeting DSM-5 diagnostic criteria within 3 years prior to randomization: major depressive disorder, bipolar disorder, schizophrenia, psychotic disorder, intellectual disability, severe alcohol use disorder, or other known psychiatric condition meeting DSM-5 diagnostic criteria which may confound the assessment of serlopitant safety or efficacy, compromise the safety of the subject, or interfere with the subject's ability to comply with protocol-mandated activities.

5. Suicidal ideation within 3 years prior to randomization, or history of suicide attempt at any time.

6. Known active hepatitis infection.

7. Known history of human immunodeficiency virus (HIV) infection.

8. Documented history of parasitic infection, including skin parasites such as scabies, within 12 months prior to randomization.

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

10. Currently pregnant or breastfeeding female subject.

11. Presence of any medical condition or disability that, in the investigator's opinion, could interfere with the assessment of serlopitant safety or efficacy, compromise the safety of the subject, or interfere with the subject's ability to comply with protocol-mandated activities; this includes any clinically significant screening ECG abnormalities any may include some clinically significant screening laboratory abnormalities.

1. Unless specifically excluded per exclusion #9, clinically significant laboratory abnormalities at screening which are unlikely to interfere with the assessment of safety or efficacy in this trial, compromise the safety of the subject, or interfere with the subject's ability to comply with protocol mandated activities are permitted.

1. Planned or anticipated major surgical procedure or other activity that would interfere with the subject's ability to comply with protocol-mandated assessments (e.g., extended international travel) during the subject's participation in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Study Site 221	Bryant	Arkansas	United States	72022
2	Study Site 220	Beverly Hills	California	United States	90212
3	Study Site 204	Fremont	California	United States	94538
4	Study Site 356	San Diego	California	United States	92108
5	Study Site 202	San Diego	California	United States	92123
6	Study Site 215	San Diego	California	United States	92123
7	Study Site 376	Santa Monica	California	United States	90404
8	Study Site 212	Clearwater	Florida	United States	33761
9	Study Site 210	Coral Gables	Florida	United States	33134
10	Study Site 331	Miami	Florida	United States	33144
11	Study Site 348	Miami	Florida	United States	33165
12	Study Site 222	North Miami Beach	Florida	United States	33162
13	Study Site 206	Sanford	Florida	United States	32771
14	Study Site 213	Boise	Idaho	United States	83704
15	Study Site 360	New Albany	Indiana	United States	47150
16	Study Site 207	South Bend	Indiana	United States	46617
17	Study Site 228	Louisville	Kentucky	United States	40202
18	Study Site 216	Louisville	Kentucky	United States	40241
19	Study Site 506	Ann Arbor	Michigan	United States	48103
20	Study Site 219	Clinton Township	Michigan	United States	48038
21	Study Site 209	Fridley	Minnesota	United States	55432
22	Study Site 371	Saint Joseph	Missouri	United States	64506
23	Study Site 227	Omaha	Nebraska	United States	68144
24	Study Site 201	East Windsor	New Jersey	United States	08520
25	Study Site 375	Forest Hills	New York	United States	11375
26	Study Site 500	New York	New York	United States	10023
27	Study Site 516	Bexley	Ohio	United States	43209
28	Study Site 211	Broomall	Pennsylvania	United States	19008
29	Study Site 345	Johnston	Rhode Island	United States	02919
30	Study Site 205	Murfreesboro	Tennessee	United States	37130
31	Study Site 182	College Station	Texas	United States	77845
32	Study Site 224	Houston	Texas	United States	77004
33	Study Site 359	Pflugerville	Texas	United States	78660
34	Study Site 339	Plano	Texas	United States	75024
35	Study Site 203	San Antonio	Texas	United States	78218
36	Study Site 223	Sugar Land	Texas	United States	77479
37	Study Site 226	Webster	Texas	United States	77598
38	Study Site 217	Norfolk	Virginia	United States	23502
39	Study Site 336	Richmond	Virginia	United States	23220

Sponsors and Collaborators

• Vyne Therapeutics Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Mar 15, 2018
• Statistical Analysis Plan - Nov 9, 2018

More Information

Publications

None provided.

• Responsible Party: Vyne Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT03343639
• Other Study ID Numbers: MTI-109
• First Posted: Nov 17, 2017
• 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: Psoriasis; Pruritus; Serlopitant

Study Results

Participant Flow

Arm/Group Title	Serlopitant 5 mg	Placebo
Arm/Group Description	Subjects received a 3-tablet oral loading dose (15 mg) on the first day of the treatment period followed by a 5 mg dose of Serlopitant taken once daily by mouth for 8 weeks	Subjects received a 3-tablet oral loading dose on the first day of the treatment period followed by a Placebo tablet taken once daily by mouth for 8 weeks
Period Title: Overall Study
STARTED	102	102
COMPLETED	88	90
NOT COMPLETED	14	12

Baseline Characteristics

Arm/Group Title	Serlopitant 5 mg	Placebo	Total
Arm/Group Description	Subjects received a 3-tablet oral loading dose (15 mg) on the first day of the treatment period followed by a 5 mg dose of Serlopitant taken once daily by mouth for 8 weeks	Subjects received a 3-tablet oral loading dose on the first day of the treatment period followed by a Placebo tablet taken once daily by mouth for 8 weeks	Total of all reporting groups
Overall Participants	102	101	203
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.2 (15.2)	46.7 (12.34)	47.5 (13.84)
Sex: Female, Male (Count of Participants)
Female	48 47.1%	62 61.4%	110 54.2%
Male	54 52.9%	39 38.6%	93 45.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	29 28.4%	31 30.7%	60 29.6%
Not Hispanic or Latino	73 71.6%	70 69.3%	143 70.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1%	0 0%	1 0.5%
Asian	3 2.9%	4 4%	7 3.4%
Native Hawaiian or Other Pacific Islander	0 0%	1 1%	1 0.5%
Black or African American	12 11.8%	6 5.9%	18 8.9%
White	84 82.4%	89 88.1%	173 85.2%
More than one race	2 2%	1 1%	3 1.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	102 100%	101 100%	203 100%
WI-NRS (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	8.303 (1.0277)	8.082 (1.0588)	8.193 (1.0466)

Outcome Measures

1. Primary Outcome

Title	WI-NRS 4-point Responder Rate at Week 8
Description	Worst Itch Numeric Rating Scale (WI-NRS). 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicate greater itch intensity. A 4-point responder is a subject who had at least a 4-point reduction in score between Baseline and Week 8.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

These figures represent full analysis set.

Arm/Group Title	Serlopitant 5 mg	Placebo
Arm/Group Description	Subjects received a 3-tablet oral loading dose (15 mg) on the first day of the treatment period followed by a 5 mg dose of Serlopitant taken once daily by mouth for 8 weeks	Subjects received a 3-tablet oral loading dose on the first day of the treatment period followed by a Placebo tablet taken once daily by mouth for 8 weeks
Measure Participants	102	101
Number [% of subjects (incl. imputed data)]	33.29	21.07

2. Secondary Outcome

Title	WI-NRS 4-point Responder Rate at Week 4
Description	Worst Itch Numeric Rating Scale (WI-NRS). 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicate greater itch intensity. A 4-point responder is a subject who had at least a 4-point reduction in score between Baseline and Week 4.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

These figures represent full analysis set

Arm/Group Title	Serlopitant 5 mg	Placebo
Arm/Group Description	Subjects received a 3-tablet oral loading dose (15 mg) on the first day of the treatment period followed by a 5 mg dose of Serlopitant taken once daily by mouth for 8 weeks	Subjects received a 3-tablet oral loading dose on the first day of the treatment period followed by a Placebo tablet taken once daily by mouth for 8 weeks
Measure Participants	102	101
Number [percentage of subjects]	20.78	11.49

3. Secondary Outcome

Title	Change in WI-NRS From Baseline to Day 7
Description	Worst Itch Numeric Rating Scale (WI-NRS). 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicate greater itch intensity. The secondary outcome is the change in WI-NRS score at 7 days compared with Baseline.
Time Frame	Change from baseline to day 7

Outcome Measure Data

Analysis Population Description

These figures represent full analysis set

Arm/Group Title	Serlopitant 5 mg	Placebo
Arm/Group Description	Subjects received a 3-tablet oral loading dose (15 mg) on the first day of the treatment period followed by a 5 mg dose of Serlopitant taken once daily by mouth for 8 weeks	Subjects received a 3-tablet oral loading dose on the first day of the treatment period followed by a Placebo tablet taken once daily by mouth for 8 weeks
Measure Participants	102	101
Least Squares Mean (Standard Deviation) [units on a scale]	-1.307 (1.8741)	-0.785 (1.8391)

4. Secondary Outcome

Title	Change in WI-NRS From Baseline to Day 3
Description	Worst Itch Numeric Rating Scale (WI-NRS). 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicate greater itch intensity. The secondary outcome is the change in WI-NRS score at 3 days compared with Baseline.
Time Frame	3 days

Outcome Measure Data

Analysis Population Description

These figures represent full analysis set.

Arm/Group Title	Serlopitant 5 mg	Placebo
Arm/Group Description	Subjects received a 3-tablet oral loading dose (15 mg) on the first day of the treatment period followed by a 5 mg dose of Serlopitant taken once daily by mouth for 8 weeks	Subjects received a 3-tablet oral loading dose on the first day of the treatment period followed by a Placebo tablet taken once daily by mouth for 8 weeks
Measure Participants	102	101
Least Squares Mean (Standard Deviation) [units on a scale]	-0.702 (1.4111)	-0.461 (1.4060)

Adverse Events

Time Frame	Adverse Events (AEs) and Serious Adverse Events (SAEs) were recorded from the first study drug administration through the Follow-up visit, for a total of approximately 10 weeks.
Adverse Event Reporting Description	The safety population is a subset of participants who received at least one dose of study medication with at least one post-baseline assessment or a reported treatment emergent adverse event. This population was analyzed based upon the actual treatment received.
Arm/Group Title	Serlopitant 5 mg		Placebo
Arm/Group Description	Subjects received a 3-tablet oral loading dose (15 mg) on the first day of the treatment period followed by a 5 mg dose of Serlopitant taken once daily by mouth for 8 weeks		Subjects received a 3-tablet oral loading dose on the first day of the treatment period followed by a Placebo tablet taken once daily by mouth for 8 weeks
All Cause Mortality
	Serlopitant 5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/102 (0%)		1/100 (1%)
Serious Adverse Events
	Serlopitant 5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/102 (0%)		2/100 (2%)
Injury, poisoning and procedural complications
Overdose	0/102 (0%)	0	1/100 (1%)	1
Road traffic accident	0/102 (0%)	0	1/100 (1%)	1
Other (Not Including Serious) Adverse Events
	Serlopitant 5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/102 (8.8%)		17/100 (17%)
Gastrointestinal disorders
Diarrhoea	3/102 (2.9%)	3	3/100 (3%)	4
Infections and infestations
Nasopharyngitis	2/102 (2%)	2	6/100 (6%)	6
Upper Respiratory Tract Infection	1/102 (1%)	1	4/100 (4%)	4
Nervous system disorders
Headache	3/102 (2.9%)	3	5/100 (5%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.