Trial of PDE4 Inhibition With Roflumilast for the Management of Plaque Psoriasis

Study Overview
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Brief Summary
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This is a double-blind, parallel group, vehicle-controlled study to assess the safety and efficacy of roflumilast (ARQ-151) 0.3% cream vs vehicle (placebo) cream for treatment of chronic plaque psoriasis (CPP) in adult participants with 2 to 20% body surface area (BSA) of CPP.

Official Title
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A Phase 3, 8-Week, Parallel Group, Double Blind, Vehicle-Controlled Study of the Safety and Efficacy of ARQ-151 Cream 0.3% Administered QD in Subjects With Chronic Plaque Psoriasis

Conditions
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Chronic Plaque Psoriasis

Intervention / Treatment
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* Drug: Roflumilast 0.3% cream
* 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 and if appropriate assent as required by local laws Males and females ages 2 years and older (inclusive) Clinical diagnosis of psoriasis vulgaris of at least 6 months duration (3 months for children) as determined by the Investigator Females of childbearing potential (FOCBP) must have a negative 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 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, tanning bed or other LED. Females who are pregnant, wishing to become pregnant during the study, or are breast-feeding. Previous treatment with ARQ-151 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 investigational product 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: 2 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rofumilast Cream 0.3%<br>Participants receive roflumilast cream 0.3% once daily for 8 weeks. | Drug: Roflumilast 0.3% cream<br>* Roflumilast 0.3% cream for topical application.<br>* Other names: ARQ-151;|
| Placebo Comparator: Vehicle cream<br>Participants receive vehicle cream once daily for 8 weeks. | Drug: Vehicle Cream<br>* Vehicle cream for topical application.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieving Success in Investigator Global Assessment (IGA) Scale Assessment of Disease Severity at Week 8 | The number of participants achieving success in IGA assessment of disease severity at Week 8 is presented (observed data only) for each arm. Success was defined as achievement of an IGA score of 0 ('clear') or 1 ('almost clear') at Week 8, accompanied by a ≥2-grade improvement from baseline IGA score. The IGA is a 5-point scale assessing the severity of plaque psoriasis, with scores ranging from 0 ('clear') to 4 ('severe'), and higher scores indicate greater symptom severity. | Baseline (Day 1) and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Achieve Psoriasis Area Severity Index-50 (PASI-50) | The Psoriasis Area and Severity Index (PASI) is widely used for the measurement of severity of psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range from 0 (no disease) to 72 (maximal disease), with higher scores indicating greater symptom severity. The time to achieve PASI-50 (defined as a 50% reduction from baseline in PASI score) is presented, and is based on observed data only. | From start of treatment to achievement of PASI-50 or study completion/early termination (maximum duration = 121 days) | 
| Number of Participants Achieving Psoriasis Area Severity Index 75 (PASI-75) | The Psoriasis Area and Severity Index (PASI) is widely used for the measurement of severity of psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range from 0 (no disease) to 72 (maximal disease), with higher scores indicating greater symptom severity. The number of participants achieving PASI-75 (defined as a 75% reduction from baseline in PASI score) at Week 8 is presented. Participant counts are based on observed data only. | Baseline (Day 1) and Week 8 | 
| Number of Participants Achieving Psoriasis Area Severity Index-90 (PASI-90) | Psoriasis Area and Severity Index (PASI) is widely used for the measurement of severity of psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease) [higher scores indicate greater symptom severity]. The number of participants achieving PASI-90 (defined as a 90% reduction from baseline in PASI score) at Week 8 is presented. Participant counts are based on observed data only. | Baseline (Day 1) and Week 8 | 
| Number of Participants Achieving Intertriginous IGA (I-IGA) Success at Week 8 | The number of participants achieving I-IGA success at Week 8 is presented. Success is defined as achievement of I-IGA score of 0 ('clear') or 1 ('almost clear') at Week 8 PLUS a ≥2-grade improvement in score from Baseline. The I-IGA is a 5-point scale assessing the severity of plaque psoriasis in the intertriginous area, with scores ranging from 0 ('clear') to 4 ('severe'), with higher scores indicating greater symptom severity. Participant counts are based on observed data only. | Baseline (Day 1) and Week 8 | 
| Number of Participants Achieving Score of 'Clear' in I-IGA at Week 8 | The number of participants achieving an IGA score of 0 ('clear') at Week 8 is presented (observed data only) for each arm. The I-IGA is a 5-point scale assessing the severity of plaque psoriasis, with scores ranging from 0 ('clear') to 4 ('severe'); higher scores indicate greater symptom severity. | Week 8 | 
| Number of Participants Achieving Worst Itch Numerical Rating Score (WI-NRS) Success | The number of participants achieving success in WI-NRS is presented. Success is defined as achievement of a ≥ 4-point reduction in WI-NRS pruritus score in participants with WI-NRS pruritus score ≥ 4 at baseline. The WI-NRS is a 10 point scale ranging from 0 ('no itch') to 10 ('worst itch imaginable'), with higher scores indicating greater symptoms severity. Results are based on observed data only. | Baseline (Day 1) and Weeks 2, 4, and 8 | 
| Change From Baseline in Psoriasis Symptoms Diary (PSD) 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 10 (worst imaginable symptoms). Scores range from 0 to 160, with higher scores indicating greater symptom severity. The least squares (LS) mean (95% CI) change in PSD total score relative to baseline is presented for each treatment arm, with decreases from baseline indicating symptom improvement. | Weeks 4 and 8 |