Safety and Efficacy of ARQ-151 Cream in Adolescents and Adults With Atopic Dermatitis

Study Overview
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Brief Summary
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The study will assess the safety, pharmacokinetics (PK), and efficacy of different doses of roflumilast (ARQ-151) cream (0.05% and 0.15%) vs placebo applied once daily (QD) for 28 days by adolescents and adults with atopic dermatitis.

Detailed Description
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This is a parallel group, double blind, vehicle-controlled study in which roflumilast cream 0.05% or 0.15% or vehicle is applied QD x 28 days to adolescent and adult subjects with atopic dermatitis. A subset of subjects will have serial PK testing, which will include the first few adolescents and adults enrolled in the study.

Official Title
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A Phase 2, 4-Week, Parallel Group, Double Blind, Vehicle-Controlled Study of the Safety and Efficacy of ARQ-151 Cream 0.05% and ARQ-151 Cream 0.15% Administered QD (Quaque Die) in Adolescent and Adult Subjects With Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Roflumilast Cream 0.05%
* 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 or, in the case of adolescents, assent with consent of a parent(s) or legal guardian, as required by local laws. Males and females ages 12 years and older (inclusive) at the time of consent. Clinical diagnosis of active atopic dermatitis for at least 6 months. BSA (Body Surface Area) involvement of at least 2% but no more than 25% at Baseline. vIGA-AD (validated Investigator Global Assessment-Atopic Dermatitis) score of 'mild' ('2') or 'moderate ('3') at Baseline. EASI (Eczema Area and Severity Index) score of ≥ 5 at Baseline. Females of childbearing potential must have a negative serum pregnancy test at Screening and, if sexually active, agree to use birth control throughout the trial. In good health as judged by the Investigator, based on medical history, physical examination, and clinical tests. Exclusion Criteria: Subjects with any serious medical condition or clinically significant physical examination or test abnormality that would prevent study participation or place the subject at significant risk. Evidence of skin conditions other than AD (atopic dermatitis) that would interfere with evaluation of the effect of the study medication. Pregnant or lactating women or women planning to become pregnant during the study. Known allergies to excipients in ARQ-151 cream. Subjects who cannot discontinue the use of strong P-450 cytochrome inducers or inhibitors . Subjects who are unwilling to refrain from using a tanning bed as well as outdoor tanning or excessive sun exposure. Subjects with unstable AD or who cannot discontinue systemic and/or topical therapies for the treatment of AD. Known or suspected: severe renal insufficiency or moderate to severe hepatic disorders (Child-Pugh B or C) history of chronic infectious disease (e.g., hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)) within last 5 years, a history of severe depression, suicidal ideation Previous treatment with ARQ-151. Subjects with a history of chronic alcohol or drug abuse in past 6 months. Current or a history of cancer within 5 years with the exception of fully excised skin basal cell carcinoma, cutaneous squamous cell carcinoma or carcinoma in situ of the cervix. Subjects with active infection that requires oral or intravenous administration of antibiotics, antifungal or antiviral agents. Subjects with a history of a major surgery within 8 weeks prior to Baseline or has a major surgery planned during the study. Subjects with any condition which makes them unsuitable for clinical study participation or are family members of the clinical study site, clinical study staff, sponsor, or family members of enrolled subjects.

Ages Eligible for Study
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Minimum Age: 12 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Roflumilast Cream 0.05%<br>Participants apply roflumilast cream 0.05% QD for 28 days. | Drug: Roflumilast Cream 0.05%<br>* Roflumilast 0.05% cream for topical application<br>* Other names: ARQ-151;|
| Active Comparator: Roflumilast Cream 0.15%<br>Participants apply roflumilast cream 0.15% QD for 28 days. | Drug: Roflumilast Cream 0.15%<br>* Roflumilast 0.15% cream for topical application<br>* Other names: ARQ-151;|
| Placebo Comparator: Vehicle Cream<br>Participants apply vehicle cream QD for 28 days. | Drug: Vehicle Cream<br>* Inactive vehicle cream matched to roflumilast cream for topical application.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 4 | The least squares (LS) mean (SD) change from baseline in EASI Total Score at Week 4 is reported. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI. | Baseline and Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in EASI Total Score | The LS mean (SD) percentage change from baseline in EASI Total Score at Weeks 1, 2, and 4 is reported. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI. | Baseline and Weeks 1, 2, and 4 | 
| Mean Change From Baseline in EASI Total Score at Weeks 1 and 2 | The LS mean (SD) change from baseline in EASI Total Score at Weeks 1 and 2 is reported. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI. | Baseline and Weeks 1 and 2 | 
| Number of Participants Achieving a 50% Decrease From Baseline in EASI Score (EASI-50) | The number of participants with a decrease of at least 50% from the baseline EASI total score is presented. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease), with positive results indicating an increase from baseline in EASI total score (i.e., increased symptoms) and negative results indicating a decrease from baseline score (i.e., decreased symptoms). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI. | Baseline and Weeks 1, 2, and 4 | 
| Number of Participants Achieving a 75% Decrease From Baseline in EASI Score (EASI-75) | The number of participants with a decrease of at least 75% from the baseline EASI total score is presented. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease), with positive results indicating an increase from baseline in EASI total score (i.e., increased symptoms) and negative results indicating a decrease from baseline score (i.e., decreased symptoms). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI. | Baseline and Weeks 1, 2, and 4 | 
| Number of Participants Achieving a 90% Decrease From Baseline in EASI Score (EASI-90) | The number of participants with a decrease of at least 90% from the baseline EASI total score is presented. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease), with positive results indicating an increase from baseline in EASI total score (i.e., increased symptoms) and negative results indicating a decrease from baseline score (i.e., decreased symptoms). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI. In some instances, it was not possible to compare roflumilast to vehicle due to low number of cases. | Baseline and Weeks 1, 2, and 4 | 
| Number of Participants Achieving a 100% Decrease From Baseline in EASI Score (EASI-100) | The number of participants with a decrease of 100% from the baseline EASI total score is presented. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease), with positive results indicating an increase from baseline in EASI total score (i.e., increased symptoms) and negative results indicating a decrease from baseline score (i.e., decreased symptoms). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI. In some instances, it was not possible to compare roflumilast to vehicle due to low number of cases. | Baseline and Weeks 1, 2, and 4 | 
| Mean Change From Baseline in Body Surface Area (BSA) Involvement | The LS mean (SE) change from baseline in BSA involvement at Weeks 1, 2, and 4 is presented. The BSA affected by AD was determined by the subject's hand method, where the subject's hand (including fingers) surface area was assumed to equal 1% of BSA. Negative scores indicate improvement of symptoms, whereas positive scores indicate worsening. | Baseline and Weeks 1, 2, and 4 | 
| Worse Itch Numerical Rating Score (WI-NRS) Score Change | The LS mean (SE) change from baseline in WI-NRS score is presented. 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. Higher scores indicate greater symptom severity. | Baseline and Weeks 1, 2, and 4 | 
| Number of Participants Achieving ≥4-Point Improvement in WI-NRS Pruritus Score | The number of participants achieving a ≥4-point improvement from Baseline in WI-NRS score is presented. 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. Higher scores indicate greater symptom severity. | Baseline and Weeks 1, 2, and 4 |