Trial of PDE4 Inhibition With Roflumilast for the Management of Atopic Dermatitis (INTEGUMENT-II)

Study Overview
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Brief Summary
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This study will assess the safety and efficacy of ARQ-151 cream vs vehicle applied once a day for 4 weeks by subjects with atopic dermatitis (eczema).

Detailed Description
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This is a parallel group, double blind, vehicle-controlled study in which ARQ-151 cream or vehicle is applied once daily for 4 weeks to subjects with atopic dermatitis.

Official Title
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A Phase 3, 4-Week, Parallel Group, Double Blind, Vehicle-Controlled Study of the Safety and Efficacy of ARQ-151 Cream 0.15% Administered QD in Subjects With Atopic Dermatitis

Conditions
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Atopic Dermatitis Eczema

Intervention / Treatment
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* Drug: Roflumilast (ARQ-151) 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 6 years and older at time of signing Informed Consent (Screening). Only subjects 18 years and older will be enrolled at sites located in the province of Québec in Canada. Diagnosed with atopic dermatitis 6 months duration (3 months for children), as determined by the Investigator. Stable disease for the past 4 weeks with no significant flares in atopic dermatitis before screening. Females of childbearing potential (FOCBP) must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline/Day 1. In addition, sexually active FOCBP must agree to use at least one form of a highly effective or barrier method of contraception throughout the trial. In good health as judged by the Investigator. Subjects considered reliable and capable of adhering to the Protocol and visit schedule, according to the judgment of the Investigator. Exclusion Criteria: Subjects with any serious medical condition or clinically significant abnormality that would prevent study participation or place the subject at significant risk, as judged by the Investigator Has unstable AD or any consistent requirement for high potency topical steroids. Subjects who are unwilling to refrain from prolonged sun exposure and from using a tanning bed or other artificial light emitting devices (LEDs) for 4 weeks prior to Baseline/Day 1 and during the study. Females who are pregnant, wishing to become pregnant during the study, or are breast-feeding. Previous treatment with ARQ-151. Subjects with a history of chronic alcohol or drug abuse within 6 months prior to Screening. Parent(s)/legal guardian(s) who are unable to communicate, read, or understand the local language(s). 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. Subjects who are family members of the clinical study site, clinical study staff, or sponsor, or family members of enrolled subjects living in the same house.

Ages Eligible for Study
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Minimum Age: 6 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 |
| --- | --- |
| Active Comparator: Roflumilast (ARQ-151) cream 0.15%<br>Active comparator | Drug: Roflumilast (ARQ-151) cream<br>* Roflumilast (ARQ-151) cream 0.15% - Active<br>* Other names: Roflumilast cream;|
| Placebo Comparator: Vehicle cream<br>Placebo comparator | Drug: Vehicle cream<br>* Vehicle cream<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IGA Success, defined as a vIGA-AD score of 'clear' or 'almost clear' PLUS a 2-grade improvement from Baseline at Week 4. | The vIGA-AD is a static evaluation of qualitative overall AD severity. This global assessment scale is an ordinal scale with five severity grades (reported only in integers of 0 to 4 where 0 is clear). | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects with a vIGA-AD score of 'Moderate' at randomization, vIGA-AD Success at Week 4 | IGA Success, defined as a vIGA-AD score of 'clear' or 'almost clear' PLUS a 2-grade improvement from Baseline. The vIGA-AD is a static evaluation of qualitative overall AD severity. This global assessment scale is an ordinal scale with five severity grades (reported only in integers of 0 to 4 where 0 is clear). | Week 4 | 
| In subjects with baseline WI-NRS ≥ 4, achievement of a 4 point reduction inthe WI-NRS at Week 4 | WI-NRS is a subject-reported severity of itch at its highest intensity during the previous 24-hour period. The scale is from '0 to 10' (no itch to worst imaginable itch). | Week 4 | 
| In subjects with baseline WI-NRS ≥ 4, achievement of a 4 point reduction inthe WI-NRS at Week 2 | WI-NRS is a subject-reported severity of itch at its highest intensity during the previous 24-hour period. The scale is from '0 to 10' (no itch to worst imaginable itch). | Week 2 | 
| In subjects with baseline WI-NRS ≥ 4, achievement of a 4 point reduction inthe WI-NRS at Week 1 | WI-NRS is a subject-reported severity of itch at its highest intensity during the previous 24-hour period. The scale is from '0 to 10' (no itch to worst imaginable itch). | Week 1 | 
| Achievement of at least a 75% (percent) reduction in the Eczema Area andSeverity Index (EASI-75) at Week 4 | EASI combines the assessment of the severity of lesions and the area affected into a single total score in the range 0 (no disease) to 72 (maximal disease). To calculate the EASI, the sum of the severity rating (0 to 3 with 3 being the most severe) for four clinical signs are multiplied with the numerical value of the area affected and with the percentage of the four body areas. | Week 4 | 
| vIGA-AD of 'clear' or 'almost clear' at Week 4 | The vIGA-AD is a static evaluation of qualitative overall AD severity. This global assessment scale is an ordinal scale with five severity grades (reported only in integers of 0 to 4 where 0 is clear). | Week 4 | 
| vIGA-AD success at Week 2 | The vIGA-AD is a static evaluation of qualitative overall AD severity. This global assessment scale is an ordinal scale with five severity grades (reported only in integers of 0 to 4 where 0 is clear). | Week 2 | 
| vIGA-AD success at Week 1 | The vIGA-AD is a static evaluation of qualitative overall AD severity. This global assessment scale is an ordinal scale with five severity grades (reported only in integers of 0 to 4 where 0 is clear). | Week 1 | 
| vIGA-AD of 'clear' or 'almost clear' at Week 2 | The vIGA-AD is a static evaluation of qualitative overall AD severity. This global assessment scale is an ordinal scale with five severity grades (reported only in integers of 0 to 4 where 0 is clear). | Week 2 | 
| vIGA-AD of 'clear' or 'almost clear' at Week 1 | The vIGA-AD is a static evaluation of qualitative overall AD severity. This global assessment scale is an ordinal scale with five severity grades (reported only in integers of 0 to 4 where 0 is clear). | Week 1 |