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

Phase 2

Completed

• Conditions: Atopic Dermatitis
• Interventions: Drug: Vehicle Cream; Drug: Roflumilast Cream 0.05%; Drug: Roflumilast Cream 0.15%

• Registration Number: NCT03916081
• Lead Sponsor: Arcutis Biotherapeutics, Inc.

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-04-10
• Study First Submitted QC: 2019-04-12
• Study First Posted: 2019-04-16
• Study Start: 2019-05-31
• Primary Completion: 2019-11-04
• Study Completion: 2019-11-04
• Disposition First Submitted: 2020-10-19
• Status Verified: 2022-08
• Results First Submitted: 2022-11-29
• Results First Submitted QC: 2023-01-13
• Disposition First Submitted QC: 2023-01-13
• Last Update Submitted: 2023-01-13
• Results First Posted: 2023-02-13
• Disposition First Posted: 2023-02-13
• Last Update Posted: 2023-02-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 136

Inclusion Criteria

1. 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.
2. Males and females ages 12 years and older (inclusive) at the time of consent.
3. Clinical diagnosis of active atopic dermatitis for at least 6 months.
4. BSA (Body Surface Area) involvement of at least 2% but no more than 25% at Baseline.
5. vIGA-AD (validated Investigator Global Assessment-Atopic Dermatitis) score of 'mild' ('2') or 'moderate ('3') at Baseline.
6. EASI (Eczema Area and Severity Index) score of ≥ 5 at Baseline.
7. 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.
8. In good health as judged by the Investigator, based on medical history, physical examination, and clinical tests.

Exclusion Criteria

1. 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.

2. Evidence of skin conditions other than AD (atopic dermatitis) that would interfere with evaluation of the effect of the study medication.

3. Pregnant or lactating women or women planning to become pregnant during the study.

4. Known allergies to excipients in ARQ-151 cream.

5. Subjects who cannot discontinue the use of strong P-450 cytochrome inducers or inhibitors .

6. Subjects who are unwilling to refrain from using a tanning bed as well as outdoor tanning or excessive sun exposure.

7. Subjects with unstable AD or who cannot discontinue systemic and/or topical therapies for the treatment of AD.

8. 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

9. Previous treatment with ARQ-151.

10. Subjects with a history of chronic alcohol or drug abuse in past 6 months.

11. 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.

12. Subjects with active infection that requires oral or intravenous administration of antibiotics, antifungal or antiviral agents.

13. Subjects with a history of a major surgery within 8 weeks prior to Baseline or has a major surgery planned during the study.

14. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vehicle Cream	Vehicle Cream	Participants apply vehicle cream QD for 28 days.
Roflumilast Cream 0.05%	Roflumilast Cream 0.05%	Participants apply roflumilast cream 0.05% QD for 28 days.
Roflumilast Cream 0.15%	Roflumilast Cream 0.15%	Participants apply roflumilast cream 0.15% QD for 28 days.

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 4	Baseline and 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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Achieving a 50% Decrease From Baseline in EASI Score (EASI-50)	Baseline and Weeks 1, 2, and 4	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.
Number of Participants Achieving a 90% Decrease From Baseline in EASI Score (EASI-90)	Baseline and Weeks 1, 2, and 4	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.
Mean Change From Baseline in EASI Total Score at Weeks 1 and 2	Baseline and 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.
Worse Itch Numerical Rating Score (WI-NRS) Score Change	Baseline and Weeks 1, 2, and 4	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.
Percentage Change From Baseline in EASI Total Score	Baseline and Weeks 1, 2, and 4	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.
Mean Change From Baseline in Body Surface Area (BSA) Involvement	Baseline and Weeks 1, 2, and 4	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.
Number of Participants Achieving a 75% Decrease From Baseline in EASI Score (EASI-75)	Baseline and Weeks 1, 2, and 4	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.
Number of Participants Achieving a 100% Decrease From Baseline in EASI Score (EASI-100)	Baseline and Weeks 1, 2, and 4	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.
Number of Participants Achieving ≥4-Point Improvement in WI-NRS Pruritus Score	Baseline and Weeks 1, 2, and 4	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.

Trial Locations

Locations (20)

Arcutis Clinical Site 20; 🇺🇸 Murfreesboro, Tennessee, United States

Arcutis Clinical Site 03; 🇺🇸 Fridley, Minnesota, United States

Arcutis Clinical Site 10; 🇨🇦 Richmond Hill, Ontario, Canada

Arcutis Clinical Site 17; 🇺🇸 Sanford, Florida, United States

Arcutis Clinical Site 14; 🇨🇦 Cobourg, Ontario, Canada

Arcutis Clinical Site 06; 🇨🇦 Montréal, Quebec, Canada

Arcutis Clinical Site 02; 🇺🇸 High Point, North Carolina, United States

Arcutis Clinical Site 08; 🇺🇸 Bexley, Ohio, United States

Arcutis Clinical Site 19; 🇺🇸 Hialeah, Florida, United States

Arcutis Clinical Site 18; 🇺🇸 Miami, Florida, United States

Arcutis Clinical Site 16; 🇺🇸 Boise, Idaho, United States

Arcutis Clinical Site 12; 🇺🇸 Indianapolis, Indiana, United States

Arcutis Clinical Site 23; 🇺🇸 Pittsburgh, Pennsylvania, United States

Arcutis Clinical Site 25; 🇺🇸 Scottsdale, Arizona, United States

Arcutis Clinical Site 01; 🇺🇸 San Diego, California, United States

Arcutis Clinical Site 15; 🇺🇸 Metairie, Louisiana, United States

Arcutis Clinical Site 13; 🇺🇸 Plainfield, Indiana, United States

Arcutis Clinical Site 09; 🇺🇸 College Station, Texas, United States

Arcutis Clinical Site 04; 🇺🇸 San Antonio, Texas, United States

Arcutis Clinical Site 21; 🇺🇸 Richmond, Virginia, United States