Pruritus, Psoriasis
Conditions
Brief summary
Study of the efficacy, safety, and tolerability of serlopitant for the treatment of pruritus in adults with plaque psoriasis
Interventions
Serlopitant Tablets
Placebo Tablets
Sponsors
Vyne Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Serlopitant 5 mg 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 | 102 |
| Placebo 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 | 101 |
| Total | 203 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 5 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 6 |
Baseline characteristics
| Characteristic | Serlopitant 5 mg | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 48.2 years STANDARD_DEVIATION 15.2 | 47.5 years STANDARD_DEVIATION 13.84 | 46.7 years STANDARD_DEVIATION 12.34 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants | 60 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 73 Participants | 143 Participants | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 18 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 84 Participants | 173 Participants | 89 Participants |
| Region of Enrollment United States | 102 participants | 203 participants | 101 participants |
| Sex: Female, Male Female | 48 Participants | 110 Participants | 62 Participants |
| Sex: Female, Male Male | 54 Participants | 93 Participants | 39 Participants |
| WI-NRS | 8.303 units on a scale STANDARD_DEVIATION 1.0277 | 8.193 units on a scale STANDARD_DEVIATION 1.0466 | 8.082 units on a scale STANDARD_DEVIATION 1.0588 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 102 | 1 / 100 |
| other Total, other adverse events | 9 / 102 | 17 / 100 |
| serious Total, serious adverse events | 0 / 102 | 2 / 100 |
Outcome results
Primary
WI-NRS 4-point Responder Rate at Week 8
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
Population: These figures represent full analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Serlopitant 5 mg | WI-NRS 4-point Responder Rate at Week 8 | 33.29 % of subjects (incl. imputed data) |
| Placebo | WI-NRS 4-point Responder Rate at Week 8 | 21.07 % of subjects (incl. imputed data) |
Secondary
Change in WI-NRS From Baseline to Day 3
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
Population: These figures represent full analysis set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Serlopitant 5 mg | Change in WI-NRS From Baseline to Day 3 | -0.702 units on a scale | Standard Deviation 1.4111 |
| Placebo | Change in WI-NRS From Baseline to Day 3 | -0.461 units on a scale | Standard Deviation 1.406 |
Secondary
Change in WI-NRS 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.
Time frame: Change from baseline to day 7
Population: These figures represent full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Serlopitant 5 mg | Change in WI-NRS From Baseline to Day 7 | -1.307 units on a scale | Standard Deviation 1.8741 |
| Placebo | Change in WI-NRS From Baseline to Day 7 | -0.785 units on a scale | Standard Deviation 1.8391 |
Secondary
WI-NRS 4-point Responder Rate at Week 4
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
Population: These figures represent full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Serlopitant 5 mg | WI-NRS 4-point Responder Rate at Week 4 | 20.78 percentage of subjects |
| Placebo | WI-NRS 4-point Responder Rate at Week 4 | 11.49 percentage of subjects |