The Safety, Efficacy and Pharmacokinetics of ARQ-151 Cream in Subjects With Chronic Plaque Psoriasis

Study Overview
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Brief Summary
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This is a parallel group, double blind, vehicle-controlled study in which roflumilast (ARQ-151) cream 0.3%, roflumilast cream 0.15%, or vehicle cream is applied once daily (QD) for 84 days to subjects with chronic plaque psoriasis involving between 2 and 20% body surface area.

Official Title
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A Phase 2b 12-Week Parallel Group, Double Blind, Vehicle-Controlled Study of the Safety, Efficacy and Pharmacokinetics of ARQ-151 Cream 0.3% and ARQ-151 Cream 0.15% Administered Once Daily in Subjects With Chronic Plaque Psoriasis

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: Roflumilast Cream 0.3%
* Drug: Roflumilast Cream 0.15%
* Drug: Vehicle Cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants legally competent to sign and give informed consent Males and females ages 18 years and older (inclusive) Clinical diagnosis of psoriasis vulgaris of at least 6 months duration as determined by the Investigator Females of childbearing potential (FOCBP) must have a negative urine pregnancy test at Screening (Visit 1) and Baseline (Visit 2). In addition, sexually active FOCBP must agree to use at least one form of highly effective contraception throughout the trial. In good health as judged by the Investigator, based on medical history, physical examination, serum chemistry labs, hematology values, and urinalysis. Subjects are considered reliable and capable of adhering to the Protocol and visit schedule, according to the judgment of the Investigator. Exclusion Criteria: Planned excessive exposure of treated area(s) to either natural or artificial sunlight or tanning bed. Females who are pregnant, wishing to become pregnant during the study, or are breast-feeding. Previous treatment with roflumilast cream or its active ingredient Subjects with any serious medical condition or laboratory abnormality that would prevent study participation or place the subject at significant risk, as determined by the Investigator. Subjects with a history of chronic alcohol or drug abuse within 6 months of initiation of study medication. Subjects who are unable to communicate, read or understand the local language, or who display another condition, which in the Investigator's opinion, makes them unsuitable for clinical study participation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel group, double blind, vehicle-controlled study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Roflumilast Cream 0.3%<br>Roflumilast cream 0.3% topically applied QD for 12 weeks. | Drug: Roflumilast Cream 0.3%<br>* Applied once daily for 12 weeks<br>* Other names: ARQ-151;|
| Experimental: Roflumilast Cream 0.15%<br>Roflumilast cream 0.15% topically applied QD for 12 weeks. | Drug: Roflumilast Cream 0.15%<br>* Applied once daily for 12 weeks<br>* Other names: ARQ-151;|
| Placebo Comparator: Vehicle Cream<br>Vehicle cream matched to roflumilast cream (containing only excipients of active cream) applied QD for 12 weeks. | Drug: Vehicle Cream<br>* Applied once daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' at Week 6 | The percentage of participants with an IGA score of 0 ('clear') or 1 ('almost clear') at Week 6 is reported. The IGA is 5-point scale assessing the severity of plaque psoriasis, with scores ranging from 0 ('clear') to 4 ('severe'), with higher scores indicating greater plaque severity. | Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' | The percentage of participants with an IGA score of 0 ('clear') or 1 ('almost clear') is reported. The IGA is 5-point scale assessing the severity of plaque psoriasis, with scores ranging from 0 ('clear') to 4 ('severe'), with higher scores indicating greater plaque severity. | Weeks 4, 8, and 12 | 
| Change From Baseline in Modified Psoriasis Area Severity Index (mPASI) Score | The percent change from baseline in mPASI score is presented. The mPASI combines the assessment of the severity of lesions and the area affected into a single score ranging from 0 ('no disease') to 72 ('maximal disease'), with higher scores indicating greater severity. For scoring, the body is divided into four sections (head [h]: 10% of a person's skin; arms [a] 20%; trunk [t] 30%; legs (l] 40%); for each section, the percent of area involved is estimated from 0 (0% involved) to 6 (90 to 100% involved). Then, within each area, the severity is estimated by three clinical signs: erythema ('E'; redness), induration ('T'; thickness), and desquamation ('S'; scaling). Severity parameters are measured on a scale of 0 to 4, from none to maximum severity possible. Each of these areas is scored by itself, and then the four scores are combined into the final mPASI, using the formula mPASI = 0.1 (Eh + Th + Sh) Ah + 0.2 (Ea + Ta + Sa) Aa + 0.3 (Et + Tt + St) At + 0.4 (El + Tl + Sl) Al. | Baseline (Day 1) and Weeks 4, 6, 8, and 12 | 
| Percent Change From Baseline in Body Surface Area (BSA) Affected | The BSA affected by psoriasis was determined by the subject's hand method, where the subject's hand (including fingers) surface area was assumed to equal 1% of BSA. The mean percent change from baseline in BSA is presented. | Baseline (Day 1) and Weeks 4, 6, 8, and 12 | 
| Percentage of Participants With an Investigator Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' Plus a 2-Grade Improvement From Baseline | The percentage of participants with an IGA score of 0 ('clear') or 1 ('almost clear') plus a 2-grade improvement from baseline is reported. The IGA is 5-point scale assessing the severity of plaque psoriasis, with scores ranging from 0 ('clear') to 4 ('severe'), with higher scores indicating greater plaque severity. | Baseline (Day 1) and Weeks 4, 6, 8, and 12 | 
| Percentage of Participants With an Intertriginous Area Investigator Global Assessment (I-IGA) Score of 'Clear' or 'Almost Clear' Who Had at Least Mild Lesions at Baseline | The percentage of participants (who had intertriginous area involvement with an I-IGA score of at least mild at baseline) with at least a 2-grade improvement in I-IGA score at Weeks 4, 6, 8, and 12 is presented. | Weeks 4, 6, 8, and 12 | 
| Change From Baseline in Worst Itch-Numeric Rating Scale (WI-NRS) Pruritus Score | The WI-NRS is a simple, single-item scale to assess the subject-reported severity of this symptom, on a scale ranging from 0 (no itch) to 10 (worst imaginable itch) the subject experienced in the previous 24 hours. The mean (SD) change in WI-NRS score from baseline is presented. | Baseline (Day 1) and Weeks 4, 6, 8, and 12 | 
| Percentage of Participants With Baseline Worst Itch-Numeric Rating Scale (WI-NRS) Pruritus Score ≥6 Who Experienced a 4-point Reduction | The percentage of participants who had baseline WI-NRS scores ≥6 who achieved a 4-point reduction in WI-NRS score at Weeks 4, 6, 8, and 12 is reported. The WI-NRS is a simple, single item scale to assess the subject-reported severity of this symptom, on a scale ranging from 0 (no itch) to 10 (worst imaginable itch) the subject experienced in the previous 24 hours. | Baseline (Day 1) and Weeks 4, 6, 8, and 12 | 
| Percentage of Participants Achieving a Modified Psoriasis Area Severity Index-75 (mPASI-75) Compared to Baseline | The percentage of subjects achieving a 75% reduction in mPASI (eg, mPASI-75) score relative to baseline is presented. The mPASI combines the assessment of the severity of lesions and the area affected into a single score ranging from 0 ('no disease') to 72 ('maximal disease'), with higher scores indicating greater severity. | Baseline (Day 1) and Weeks 4, 6, 8, and 12 | 
| Percentage of Participants Achieving a Modified Psoriasis Area Severity Index-90 (mPASI-90) Compared to Baseline | The mPASI combines the assessment of the severity of lesions and the area affected into a single score ranging from 0 ('no disease') to 72 ('maximal disease'), with higher scores indicating greater severity. The percentage of subjects achieving a 90% reduction in mPASI (eg, mPASI-90) score relative to baseline is presented. | Baseline (Day 1) and Weeks 4, 6, 8, and 12 | 
| Change From Baseline in Psoriasis Symptom Diary (PSD) Total Score | The PSD is a 16-item questionnaire asking subjects to rate the severity of psoriasis-related symptoms in the past 24 hours. Each question is scored from 0 (no symptoms) to 11 (worst imaginable symptoms). Scores range from 0 to 176, with higher scores indicating greater symptom severity. The mean (SD) change in PSD total score relative to baseline is presented for each treatment arm. | Baseline (Day 1) and Weeks 4, 6, 8, and 12 | 
| Change From Baseline in Itch-Related Sleep Loss Numeric Rating Scale (NRS) Score | The Itch-Related Sleep Loss NRS is a single item scale scored from 0 (no itch-related sleep loss) to 10 (itch-related sleep loss as bad as it could be) assessing the severity of itch-related sleep loss in the past 24 hours. The mean (SD) change from the baseline NRS score is presented for each treatment arm. | Baseline (Day 1) and Weeks 4, 6, 8, and 12 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) Score | The DLQI is a 10-item scale asking subject to rate the severity of symptoms during the past week. Each item is scored from 0 (not at all or not relevant) to 3 or 4 (very much) [2 questions are scored 0 to 3 and 8 questions are scored 0 to 4]. The total DLQI score ranges from 0 to 48, with higher scores indicating greater symptom severity. The mean (SD) change from baseline DLQI score is presented. | Baseline (Day 1) and Weeks 4, 6, 8, and 12 | 
| Responses to Individual Questions of the Psoriasis Symptom Diary (PSD) | Two items from the PSD asking participants to rate the overall severity of psoriasis-related itching and pain during the past 24 hours are presented. Each item is scored on an 11-point scale ranging from 0 (no symptom) to 10 (worst imaginable symptom), with lower scores indicating lower symptoms severity. The mean (SD) score is presented for each treatment arm. | Weeks 4, 6, 8, and 12 |