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

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

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). This is a parallel group, double blind, vehicle-controlled study in which ARQ-151 0.15% cream or vehicle is applied once daily (qd) for 4 weeks by participants with atopic dermatitis.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis Eczema
• Intervention / Treatment: Drug: Roflumilast Cream; Drug: Vehicle cream

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 683
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2G 1B1
      • Arcutis Clinical Site 12
  • British Columbia
    • Surrey, British Columbia, Canada, V3R 6A7
      • Arcutis Clinical Site 09
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3M 3Z4
      • Arcutis Clinical Site 26
  • Ontario
    • Ajax, Ontario, Canada, L1S 7K8
      • Arcutis Clinical Site 20
    • London, Ontario, Canada, N6H 5L5
      • Arcutis Clinical Site 23
    • Toronto, Ontario, Canada, M4W 2N4
      • Arcutis Clinical Site 25
    • Waterloo, Ontario, Canada, N2J 1C4
      • Arcutis Clinical Site 16
  • Quebec
    • Drummondville, Quebec, Canada, J2B 5L4
      • Arcutis Clinical Site 08
    • Québec, Quebec, Canada, H3Z 2S6
      • Arcutis Clinical Site 27
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35244
      • Arcutis Clinical Site 31
  • Arkansas
    • Fort Smith, Arkansas, United States, 72916
      • Arcutis Clinical Site 51
  • California
    • Inglewood, California, United States, 90301
      • Arcutis Clinical Site 46
    • San Diego, California, United States, 92123
      • Arcutis Clinical Site 19
    • San Diego, California, United States, 92123
      • Arcutis Clinical Site 36
    • Santa Monica, California, United States, 90404
      • Arcutis Clinical Site 13
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Arcutis Clinical Site 54
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Arcutis Clinical Site 55
    • Coral Gables, Florida, United States, 33146
      • Arcutis Clinical Site 30
    • Delray Beach, Florida, United States, 33484
      • Arcutis Clinical Site 37
    • Miami, Florida, United States, 33137
      • Arcutis Clinical Site 58
    • Miami, Florida, United States, 33144
      • Arcutis Clinical Site 41
    • Sanford, Florida, United States, 32771
      • Arcutis Clinical Site 11
    • West Palm Beach, Florida, United States, 33406
      • Arcutis Clinical Site 57
  • Idaho
    • Boise, Idaho, United States, 83706
      • Arcutis Clinical Site 62
  • Indiana
    • Plainfield, Indiana, United States, 46168
      • Clinical Site 04
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • Arcutis Clinical Site 43
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Arcutis Clinical Site 63
    • Lake Charles, Louisiana, United States, 70605
      • Arcutis Clinical Site 42
    • Mandeville, Louisiana, United States, 70448
      • Arcutis Clinical Site 38
    • Metairie, Louisiana, United States, 70006
      • Arcutis Clinical Site 06
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Arcutis Clinical Site 34
  • Michigan
    • Clinton Township, Michigan, United States, 48038
      • Arcutis Clinical Site 29
    • Fort Gratiot, Michigan, United States, 48059
      • Arcutis Clinical Site 21
    • Troy, Michigan, United States, 48084
      • Arcutis Clinical Site 61
  • Missouri
    • Saint Joseph, Missouri, United States, 64506
      • Arcutis Clinical Site 245
  • New York
    • New York, New York, United States, 11415
      • Arcutis Clinical Site 53
    • Rochester, New York, United States, 14623
      • Arcutis Clinical Site 39
    • Stony Brook, New York, United States, 11790
      • Arcutis Clinical Site 33
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Arcutis Clinical Site 01
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Arcutis Clinical Site 24
    • Pittsburgh, Pennsylvania, United States, 15213
      • Arcutis Clinical Site 07
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Arcutis Clinical Site 35
    • Charleston, South Carolina, United States, 29425
      • Arcutis Clinical Site 18
    • North Charleston, South Carolina, United States, 29420
      • Arcutis Clinical Site 15
  • Texas
    • Austin, Texas, United States, 78759
      • Clinical Site 05
    • College Station, Texas, United States, 77845
      • Arcutis Clinical Site 03
    • Frisco, Texas, United States, 75034
      • Arcutis Clinical Site 59
    • Grapevine, Texas, United States, 76051
      • Arcutis Clinical Site 250
    • Pflugerville, Texas, United States, 78660
      • Arcutis Clinical Site 52
    • San Antonio, Texas, United States, 78213
      • Arcutis Clinical Site 02
  • Utah
    • Orem, Utah, United States, 84058
      • Arcutis Clinical Site 32
  • Virginia
    • Burke, Virginia, United States, 22015
      • Arcutis Clinical Site 22
    • Norfolk, Virginia, United States, 23502
      • Arcutis Clinical Site 17

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants legally competent to sign and give informed consent and, if appropriate, assent as required by local laws.
2. 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.
3. 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.
4. 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.
5. In good health as judged by the Investigator.
6. Subjects considered reliable and capable of adhering to the Protocol and visit schedule, according to the judgment of the Investigator.

Exclusion Criteria:

1. 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
2. Has unstable AD or any consistent requirement for high potency topical steroids.
3. 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.
4. Females who are pregnant, wishing to become pregnant during the study, or are breast-feeding.
5. Previous treatment with ARQ-151.
6. Subjects with a history of chronic alcohol or drug abuse within 6 months prior to Screening.
7. 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.
8. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Roflumilast Cream 0.15%; Participants apply roflumilast cream 0.15% once daily (qd) for 4 weeks.	Drug: Roflumilast Cream; Roflumilast cream 0.15% for topical application; Other Names: ARQ-151
Placebo Comparator: Vehicle Cream; Participants apply vehicle cream qd for 4 weeks.	Drug: Vehicle cream; Vehicle cream for topical application

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Success at Week 4	The percentage of participants achieving viGA-AD "success" is presented with multiple imputation of missing observations. viGA-AD "success" is 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), with higher scores indicative of greater symptom severity.	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of vIGA-AD Success at Week 4 in Participants With "Moderate" Baseline Scores	The percentage of participants with moderate baseline scores achieving viGA-AD "success" is presented with multiple imputation of missing observations. viGA-AD "success" is defined as a viGA-AD score of 'clear' or 'almost clear' PLUS a 2-grade improvement from baseline in participants with a 'moderate' baseline viGA-AD score. The viGA-AD is a static evaluation of qualitative overall AD severity. This global assessment scale is an ordinal scale with five severity grades (0 'clear' to 4 'severe'), with higher scores indicative of greater symptom severity.	Week 4
vIGA-AD Success at Week 2	The percentage of participants achieving viGA-AD "success" is presented with multiple imputation of missing observations. viGA-AD "success" is 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), with higher scores indicative of greater symptom severity.	Week 2
vIGA-AD Success at Week 1	The percentage of participants achieving viGA-AD "success" is presented with multiple imputation of missing observations. viGA-AD "success" is 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), with higher scores indicative of greater symptom severity.	Week 1
Achievement of a 4-point Reduction at Week 4 in the Average, Weekly Worst Itch Numeric Rating Scale (WI-NRS) in Participants With Baseline WI-NRS Score ≥4	The percentage of participants with a baseline WI-NRS ≥ 4 achieving WI-NRS success is presented with multiple imputation of missing observations. 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 participant experienced in the previous 24 hours (higher scores indicate higher itch severity).	Week 4
Achievement of a 4-point Reduction at Week 2 in the WI-NRS in Participants With Baseline WI-NRS Score ≥4	The percentage of participants with a baseline WI-NRS ≥ 4 achieving WI-NRS success is presented with multiple imputation of missing observations. 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 participant experienced in the previous 24 hours (higher scores indicate higher itch severity).	Week 2
Achievement of a 4-point Reduction at Week 1 in the WI-NRS in Participants With Baseline WI-NRS Score ≥4	The percentage of participants with a baseline WI-NRS ≥ 4 achieving WI-NRS success is presented with multiple imputation of missing observations. 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 participant experienced in the previous 24 hours (higher scores indicate higher itch severity).	Week 1
Achievement of ≥75% Decrease From Baseline at Week 4 in the Eczema Area and Severity Index (EASI-75)	The percentage of participants achieving EASI-75 is presented with multiple imputation of missing observations. EASI-75 is a ~75% reduction from the baseline EASI score. 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
Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 4	The percentage of participants scoring 'clear' or 'almost clear' on viGA-AD is presented with multiple imputation of missing observations. The viGA-AD is a static evaluation of qualitative overall AD severity. This global assessment scale is an ordinal scale with five severity grades (0 'clear' to 4 'severe'), with higher scores indicative of greater symptom severity.	Week 4
Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 2	The percentage of participants scoring 'clear' or 'almost clear' on viGA-AD is presented with multiple imputation of missing observations. The viGA-AD is a static evaluation of qualitative overall AD severity. This global assessment scale is an ordinal scale with five severity grades (0 'clear' to 4 'severe'), with higher scores indicative of greater symptom severity.	Week 2
Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 1	The percentage of participants scoring 'clear' or 'almost clear' on viGA-AD is presented with multiple imputation of missing observations. The viGA-AD is a static evaluation of qualitative overall AD severity. This global assessment scale is an ordinal scale with five severity grades (0 'clear' to 4 'severe'), with higher scores indicative of greater symptom severity.	Week 1

Collaborators and Investigators

• Sponsor: Arcutis Biotherapeutics, Inc.
• Investigators: Study Director: David Berk, MD, Arcutis Biotherapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2021
• Primary Completion (Actual): September 29, 2022
• Study Completion (Actual): September 29, 2022

Study Registration Dates

• First Submitted: February 24, 2021
• First Submitted That Met QC Criteria: February 24, 2021
• First Posted (Actual): February 26, 2021

Study Record Updates

• Last Update Posted (Actual): October 4, 2024
• Last Update Submitted That Met QC Criteria: September 24, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: ARQ-151-312

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No