Clinical trial NCT03343639: Study of the Efficacy, Safety and Tolerability of Serlopitant for the Treatment of Pruritus (Itch) With Plaque Psoriasis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pruritus
Psoriasis
Lead sponsor: Vyne Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2017-11-17
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study of the efficacy, safety, and tolerability of serlopitant for the treatment of pruritus in adults with plaque psoriasis


Eligibility criteria: 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.

   a. Presence of plaque psoriasis in any anatomic location, covering ≤ 10% BSA in total, at the Screening and Baseline visits.
3. Pruritus of at least 4 weeks' duration prior to the initial Screening visit, and throughout the screening period prior to randomization.
4. 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.
5. WI-NRS initial screening score consistent with severe pruritus.
6. WI-NRS scores during the 2 weeks of screening consistent with sever pruritus.
7. 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.
8. Weight ≥ 32 kg at the Screening and Baseline visits.
9. Willing and able to complete daily eDiary entries within a consistent timeframe for the duration of the study.

   1. 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.

   a. Prior treatment with other neurokinin-1 receptor (NK1-R) antagonists (e.g., aprepitant, fosaprepitant, rolapitant) is not allowed within 1 year prior to randomization.
2. 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.
3. Predominance of non-plaque forms of psoriasis (e.g., guttate, drug-induced, pustular, erythrodermic).
4. 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.
5. 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.
6. 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.
7. Treatment with any of the following therapies within 4 weeks prior to randomization:

   a. 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.

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

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

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

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

   f. Strong CYP3A4 inhibitors.
8. Treatment with any investigational therapy within 4 weeks or 5 half-lives (whichever is longer) prior to randomization.
9. Serum creatinine, total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2x the upper limit of normal (ULN) during screening.
10. 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.
11. 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.
12. Suicidal ideation within 3 years prior to randomization, or history of suicide attempt at any time.
13. Known active hepatitis infection.
14. Known history of human immunodeficiency virus (HIV) infection.
15. Documented history of parasitic infection, including skin parasites such as scabies, within 12 months prior to randomization.
16. History of hypersensitivity to serlopitant or any of its components.
17. Currently pregnant or breastfeeding female subject.
18. 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.

    a. 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.
19. 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.

Primary outcomes:
measure: WI-NRS 4-point Responder Rate at Week 8
timeFrame: 8 weeks
Secondary outcomes:
measure: WI-NRS 4-point Responder Rate at Week 4
timeFrame: 4 weeks
measure: Change in WI-NRS From Baseline to Day 7
timeFrame: Change from baseline to day 7
measure: Change in WI-NRS From Baseline to Day 3
timeFrame: 3 days
Other outcomes:
Locations:
city: Bryant
country: United States
facility: Study Site 221
state: Arkansas
city: Beverly Hills
country: United States
facility: Study Site 220
state: California
city: Fremont
country: United States
facility: Study Site 204
state: California
city: San Diego
country: United States
facility: Study Site 356
state: California
city: San Diego
country: United States
facility: Study Site 202
state: California
city: San Diego
country: United States
facility: Study Site 215
state: California
city: Santa Monica
country: United States
facility: Study Site 376
state: California
city: Clearwater
country: United States
facility: Study Site 212
state: Florida
city: Coral Gables
country: United States
facility: Study Site 210
state: Florida
city: Miami
country: United States
facility: Study Site 331
state: Florida
city: Miami
country: United States
facility: Study Site 348
state: Florida
city: North Miami Beach
country: United States
facility: Study Site 222
state: Florida
city: Sanford
country: United States
facility: Study Site 206
state: Florida
city: Boise
country: United States
facility: Study Site 213
state: Idaho
city: New Albany
country: United States
facility: Study Site 360
state: Indiana
city: South Bend
country: United States
facility: Study Site 207
state: Indiana
city: Louisville
country: United States
facility: Study Site 228
state: Kentucky
city: Louisville
country: United States
facility: Study Site 216
state: Kentucky
city: Ann Arbor
country: United States
facility: Study Site 506
state: Michigan
city: Clinton Township
country: United States
facility: Study Site 219
state: Michigan
city: Fridley
country: United States
facility: Study Site 209
state: Minnesota
city: Saint Joseph
country: United States
facility: Study Site 371
state: Missouri
city: Omaha
country: United States
facility: Study Site 227
state: Nebraska
city: East Windsor
country: United States
facility: Study Site 201
state: New Jersey
city: Forest Hills
country: United States
facility: Study Site 375
state: New York
city: New York
country: United States
facility: Study Site 500
state: New York
city: Bexley
country: United States
facility: Study Site 516
state: Ohio
city: Broomall
country: United States
facility: Study Site 211
state: Pennsylvania
city: Johnston
country: United States
facility: Study Site 345
state: Rhode Island
city: Murfreesboro
country: United States
facility: Study Site 205
state: Tennessee
city: College Station
country: United States
facility: Study Site 182
state: Texas
city: Houston
country: United States
facility: Study Site 224
state: Texas
city: Pflugerville
country: United States
facility: Study Site 359
state: Texas
city: Plano
country: United States
facility: Study Site 339
state: Texas
city: San Antonio
country: United States
facility: Study Site 203
state: Texas
city: Sugar Land
country: United States
facility: Study Site 223
state: Texas
city: Webster
country: United States
facility: Study Site 226
state: Texas
city: Norfolk
country: United States
facility: Study Site 217
state: Virginia
city: Richmond
country: United States
facility: Study Site 336
state: Virginia
Study officials:
References:
citation: Pariser DM, Bagel J, Lebwohl M, Yosipovitch G, Chien E, Spellman MC. Serlopitant for psoriatic pruritus: A phase 2 randomized, double-blind, placebo-controlled clinical trial. J Am Acad Dermatol. 2020 Jun;82(6):1314-1320. doi: 10.1016/j.jaad.2020.01.056. Epub 2020 Jan 30.