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

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 is a parallel group, double blind, vehicle-controlled study to assess the safety and efficacy of roflumilast (ARQ-151) cream vs vehicle applied once daily (qd) for 4 weeks by participants with atopic dermatitis (eczema).

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis Eczema
• Intervention / Treatment: Drug: Roflumilast Cream 0.15%; 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): 654
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2J 7E1
      • Arcutis Clinical Site 41
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B 1G9
      • Arcutis Clinical Site 29
  • Ontario
    • Markham, Ontario, Canada, L3P 1X3
      • Arcutis Clinical Site 11
    • Mississauga, Ontario, Canada, L5H 1G9
      • Clinical Site 25
    • Peterborough, Ontario, Canada, K9J 5K2
      • Arcutis Clinical Site 32
    • Windsor, Ontario, Canada, N8W 1E6
      • Arcutis Clinical Site 09
  • Quebec
    • Montréal, Quebec, Canada, H2X 2V1
      • Arcutis Clinical Site 24
• United States
  • Alabama
    • Montgomery, Alabama, United States, 36117
      • Arcutis Clinical Site 57
  • Arizona
    • Scottsdale, Arizona, United States, 85255
      • Arcutis Clinical Site 34
  • Arkansas
    • Little Rock, Arkansas, United States, 72212
      • Arcutis Clinical Site 58
  • California
    • Beverly Hills, California, United States, 90212
      • Arcutis Clinical Site 40
    • Encinitas, California, United States, 92024
      • Arcutis Clinical Site 06
    • Los Angeles, California, United States, 90056
      • Arcutis Clinical Site 52
    • San Diego, California, United States, 92123
      • Arcutis Clinical Site 05
    • San Francisco, California, United States, 94132
      • Arcutis Clinical Site 08
    • Thousand Oaks, California, United States, 91320
      • Arcutis Clinical Site 62
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Arcutis Clinical Site 30
    • Jacksonville, Florida, United States, 32256
      • Arcutis Clinical Site 04
    • Largo, Florida, United States, 33770
      • Arcutis Clinical Site 15
    • Miami Lakes, Florida, United States, 33014
      • Arcutis Clinical Site 39
    • North Miami Beach, Florida, United States, 33162
      • Arcutis Clinical Site 38
    • Tampa, Florida, United States, 33613
      • Arcutis Clinical Site 01
    • Wellington, Florida, United States, 33449
      • Arcutis Clinical Site 61
  • Georgia
    • Sandy Springs, Georgia, United States, 30328
      • Arcutis Clinical Site 26
  • Illinois
    • Rolling Meadows, Illinois, United States, 33770
      • Arcutis Clinical Site 13
  • Indiana
    • Clarksville, Indiana, United States, 47129
      • Arcutis Clinical Site 48
    • Indianapolis, Indiana, United States, 46250
      • Arcutis Clinical Site 02
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • Arcutis Clinical Site 03
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Arcutis Clinical Site 36
  • Michigan
    • Auburn Hills, Michigan, United States, 48326
      • Arcutis Clinical Site 55
    • Bay City, Michigan, United States, 48706
      • Arcutis Clinical Site 54
    • Clarkston, Michigan, United States, 48346
      • Arcutis Clinical Site 46
    • Detroit, Michigan, United States, 48202
      • Arcutis Clinical Site 37
  • Minnesota
    • New Brighton, Minnesota, United States, 55112
      • Arcutis Clinical Site 10
  • Nevada
    • Reno, Nevada, United States, 89509
      • Arcutis Clinical Site 33
  • New Jersey
    • East Windsor, New Jersey, United States, 08520
      • Arcutis Clinical Site 42
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Arcutis Clinical Site 17
    • Portland, Oregon, United States, 97223
      • Arcutis Clinical Site 16
    • Portland, Oregon, United States, 97239
      • Arcutis Clinical Site 14
  • Pennsylvania
    • Newtown Square, Pennsylvania, United States, 19073
      • Arcutis Clinical Site 35
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Arcutis Clinical Site 101
  • Tennessee
    • Murfreesboro, Tennessee, United States, 37130
      • Arcutis Clinical Site 31
  • Texas
    • Arlington, Texas, United States, 76011
      • Arcutis Clinical Site 19
    • Bellaire, Texas, United States, 77401
      • Arcutis Clinical Site 43
    • Houston, Texas, United States, 77030
      • Arcutis Clinical Site 27
    • Houston, Texas, United States, 77056
      • Arcutis Clinical Site 20
    • San Antonio, Texas, United States, 78218
      • Arcutis Clinical Site 28
  • Utah
    • South Jordan, Utah, United States, 84095
      • Arcutis Clinical Site 21
  • Washington
    • Spokane, Washington, United States, 99202
      • Arcutis Clinical Site 12

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 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 with mild to moderate AD apply roflumilast cream 0.15% QD for 4 weeks.	Drug: Roflumilast Cream 0.15%; Roflumilast Cream 0.15% - Active; Other Names: ARQ-151
Placebo Comparator: Vehicle Cream; Participants with mild to moderate AD applied vehicle cream QD for 4 weeks.	Drug: Vehicle Cream; Cream - Vehicle

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
Achievement of a 4-Point Reduction in the Average, Weekly Worst Itch Numeric Rating Scale (WI-NRS) at Week 4 in Participants ≥12 Years of Age With Baseline WI-NRS ≥ 4	The percentage of participants ≥12 years of age with a baseline WI-NRS ≥4 achieving WI-NRS success at Week 4 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 in the Average, Weekly WI-NRS at Week 2 in Participants ≥12 Years of Age With Baseline WI-NRS ≥ 4	The percentage of participants ≥12 years of age with a baseline WI-NRS ≥4 achieving WI-NRS success at Week 2 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 in the Average, Weekly WI-NRS at Week 1 in Participants ≥12 Years of Age With Baseline WI-NRS ≥ 4	The percentage of participants ≥12 years of age with a baseline WI-NRS ≥4 achieving WI-NRS success at Week 1 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% Reduction in the Eczema Area and Severity Index (EASI-75) at Week 4	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 at Week 4 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 Success at Week 2	The percentage of participants achieving "success" on the VIGA-AD at Week 2 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 (0 'clear' to 4 'severe'), with higher scores indicative of greater symptom severity.	Week 2
Achievement of vIGA-AD Success at Week 1	The percentage of participants achieving "success" on the VIGA-AD at Week 1 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 (0 'clear' to 4 'severe'), with higher scores indicative of greater symptom severity.	Week 1
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 at Week 4 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 at Week 4 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): January 27, 2021
• Primary Completion (Actual): August 30, 2022
• Study Completion (Actual): August 30, 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 (Estimated): October 9, 2024
• Last Update Submitted That Met QC Criteria: September 13, 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-151-311

Drug and device information, study documents

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