Safety and Efficacy of ARQ-154 Foam in Subjects With Seborrheic Dermatitis

Study Overview
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Brief Summary
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This was a parallel group, double blind, vehicle-controlled study assessed the safety and efficacy of roflumilast foam (ARQ-154) vs placebo foam in participants with seborrheic dermatitis.

Official Title
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A Phase 2b, 8-Week, Parallel Group, Double Blind, Vehicle-Controlled Study of the Safety and Efficacy of ARQ-154 Foam 0.3% Administered QD in Subjects With Seborrheic Dermatitis

Conditions
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Seborrheic Dermatitis

Intervention / Treatment
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* Drug: Roflumilast Foam 0.3%
* Drug: Vehicle foam


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) at the time of consent. Clinical diagnosis of seborrheic dermatitis of at least 3 months duration as determined by the Investigator. Stable disease for the past 4 weeks. Seborrheic dermatitis of the scalp and/or face and/or trunk and/or intertriginous areas. An Investigator Global Assessment (IGA) of disease severity of at least Moderate ('3') at Baseline. Overall Assessment of Erythema and Overall Assessment of Scaling scores of at least Moderate ('2') at Baseline. Females of childbearing potential (FOCBP) must have a negative serum pregnancy test at Screening (Visit 1) and a negative urine pregnancy test at Baseline (Visit 2). Females of non-childbearing potential must either be post-menopausal with spontaneous amenorrhea for at least 12 months or have undergone surgical sterilization. Subjects in good health as judged by the Investigator, based on medical history, physical examination, vital signs, serum chemistry labs, hematology values, and urinalysis. Subjects are considered reliable and capable of adhering to the Protocol and visit schedule according to the Investigator judgment. Exclusion Criteria: Subjects who cannot discontinue treatment with therapies for the treatment of seborrheic dermatitis prior to the Baseline visit and during the study according to Excluded Medications and Treatments. Planned excessive exposure of treated area(s) to either natural or artificial sunlight, tanning bed or other LED. Subjects who cannot discontinue the use of strong P-450 cytochrome inhibitors e.g., indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir, suboxone and telithromycin for two weeks prior to the Baseline visit (Visit 2) and during the study. Subjects who cannot discontinue the use of strong P-450 cytochrome inducers e.g., efavirenz, nevirapine, glucocorticoids, barbiturates (including phenobarbital), phenytoin, rifampin, and carbamazepine for two weeks prior to the Baseline visit (Visit 2) and during the study. Subjects with PHQ-8 ≥10 at Screening or Baseline visits. Previous treatment with ARQ-151 and ARQ-154. Subjects who have received oral roflumilast (Daliresp®, Daxas®) or other PDE-4 inhibitors (apremilast) within the past 4 weeks. Known allergies to excipients in ARQ-154 foam. Known or suspected: severe renal insufficiency or moderate to severe hepatic disorders; hypersensitivity to component(s) of the investigational products; or history of severe depression, suicidal ideation, or Baseline/Screening C-SSRS indicative of suicidal ideation, whether lifetime or recent/current. Subjects with a history of a major surgery within 8 weeks prior to Baseline (Visit 2) or has a major surgery planned during the study. Subjects with any condition on the treatment area which, in the opinion of the Investigator, could confound efficacy measurements. Subjects unable to apply product to the scalp due to physical limitations. Females who are pregnant, wishing to become pregnant during the study, or are breast-feeding. A clinically relevant history of abuse of alcohol or other drugs, at the discretion of the Investigator. 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. Any condition that in the Investigator's assessment would preclude the subject from participating in the study.

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Roflumilast Foam 0.3%<br>Participants apply roflumilast foam 0.3% once daily (QD) to all areas of seborrheic dermatitis once daily for 8 weeks. | Drug: Roflumilast Foam 0.3%<br>* Roflumilast foam for topical application.<br>* Other names: ARQ-154;|
| Placebo Comparator: Vehicle Foam<br>Participants apply inactive vehicle foam matched to roflumilast foam QD for 8 weeks. | Drug: Vehicle foam<br>* Vehicle foam for topical application.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of Investigator Global Assessment (IGA) Success at Week 8 | The number of participants achieving success in IGA assessment of disease severity at Week 8 is presented for each arm. Success was defined as achievement of an IGA score of 0 ('completely clear') or 1 ('almost clear'), accompanied by a ≥2-grade improvement from baseline IGA score. The IGA is 5-point scale assessing the severity of Seborrheic Dermatitis, with scores ranging from 0 ('completely clear') to 4 ('severe'), and higher scores indicate greater severity. The IGA scores are based on observed data, whereas odds ratio and p-values were calculated using multiple imputation of missing values. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of IGA Success at Weeks 2 and 4 | The number of participants achieving success in IGA assessment of disease severity at Weeks 2 and 4 is presented for each arm. Success was defined as achievement of an IGA score of 0 ('completely clear') or 1 ('almost clear'), accompanied by a ≥2-grade improvement from baseline IGA score. The IGA is 5-point scale assessing the severity of Seborrheic Dermatitis, with scores ranging from 0 ('completely clear') to 4 ('severe'), and higher scores indicate greater severity. The IGA scores are based on observed data, whereas odds ratio and p-values were calculated using multiple imputation of missing values. | Weeks 2 and 4 | 
| Change From Baseline in Overall Assessment of Erythema Score | The mean (SD) change from baseline in Overall Assessment of Erythema score at Weeks 2, 4, and 8 is shown. The Erythema Assessment is a simple, single-item scale to assess the subject-reported severity of this symptom, on a scale ranging from 0 (None: no evidence of erythema.) to 3 (Severe: Intense [fiery red] erythema.). Higher scores indicate greater severity. | Weeks 2, 4, and 8 | 
| Achievement of Overall Assessment of Erythema Success | The number of participants achieving success in Overall Assessment of Erythema at Weeks 2, 4, and 8 is presented for each arm. Success was defined as achievement of an overall score of 0 or 1 plus a ≥2 grade improvement from Baseline. The Overall Assessment of Erythema is a simple, single-item scale to assess the subject-reported severity of this symptom, on a scale ranging from 0 (None: no evidence of erythema.) to 3 (Severe: Intense [fiery red] erythema.). Higher scores indicate greater severity. | Weeks 2, 4, and 8 | 
| Change From Baseline in Overall Assessment of Scaling Score | The mean (SD) change from baseline in Overall Assessment of Scaling score at Weeks 2, 4, and 8 is shown. The Overall Assessment of Scaling is a simple, single-item scale to assess the subject-reported severity of this symptom, on a scale ranging from 0 (No scaling: No scaling evident on lesions.) to 3 (Severe: Coarse, thick scales, with flaking into clothes or skin.). Higher scores indicate greater severity. | Weeks 2, 4, and 8 | 
| Achievement of Overall Assessment of Scaling Success | The number of participants achieving success in Overall Assessment of Scaling score at Weeks 2, 4, and 8 is presented for each arm. Success was defined as achievement of an Overall Assessment of Scaling score of 0 or 1 plus a ≥2 grade improvement from Baseline. The Overall Assessment of Scaling is a simple, single-item scale to assess the subject-reported severity of this symptom, on a scale ranging from 0 (No scaling: No scaling evident on lesions.) to 3 (Severe: Coarse, thick scales, with flaking into clothes or skin.). Higher scores indicate greater severity. | Weeks 2, 4, and 8 | 
| Change From Baseline in Worst Itch Numeric Rating Scale (WI-NRS) Score | The change from baseline in WI-NRS is shown. 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. Negative values represent a decrease in worst itch from baseline, and positive values indicate an increase. | Weeks 2, 4, and 8 | 
| Achievement of WI-NRS Success | The number of participants achieving WI-NRS success at Weeks 2, 4, and 8 is presented. Success was defined as achievement of a ≥4-point improvement from baseline WI-NRS 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. | Weeks 2, 4, and 8 |