Atopic Dermatitis Eczema
Conditions
Brief summary
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).
Interventions
Roflumilast Cream 0.15% - Active
DRUGVehicle Cream
Cream - Vehicle
Sponsors
Arcutis Biotherapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Achievement of Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Success at Week 4 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Week 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). |
| 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 | Week 2 | 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). |
| 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 | Week 1 | 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). |
| Achievement of ≥ 75% Reduction in the Eczema Area and Severity Index (EASI-75) at Week 4 | 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. |
| Achievement of vIGA-AD Success at Week 4 in Participants With Moderate Baseline Scores | Week 4 | 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. |
| Achievement of vIGA-AD Success at Week 2 | 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. |
| Achievement of vIGA-AD Success at Week 1 | 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. |
| Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 2 | 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. |
| Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 1 | 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. |
| Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 4 | 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. |
Countries
Canada, United States
Participant flow
Recruitment details
This study was conducted at 65 centers in the United States, Canada, and Poland.
Participants by arm
| Arm | Count |
|---|---|
| Roflumilast Cream 0.15% Participants with mild to moderate AD applied roflumilast cream 0.15% once daily (QD) for 4 weeks. | 433 |
| Vehicle Cream Participants with mild to moderate AD applied vehicle cream QD for 4 weeks. | 221 |
| Total | 654 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 3 |
| Overall Study | Consent withdrawn due to AEs of nausea, headaches, dizziness, and brain fog | 1 | 0 |
| Overall Study | Lack of Efficacy | 5 | 2 |
| Overall Study | Lost to Follow-up | 11 | 3 |
| Overall Study | Noncompliance | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 5 |
Baseline characteristics
| Characteristic | Roflumilast Cream 0.15% | Vehicle Cream | Total |
|---|---|---|---|
| Age, Continuous | 28.1 years STANDARD_DEVIATION 19.14 | 28.5 years STANDARD_DEVIATION 18.94 | 28.2 years STANDARD_DEVIATION 19.06 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 99 Participants | 56 Participants | 155 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 333 Participants | 164 Participants | 497 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaska native | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 63 Participants | 32 Participants | 95 Participants |
| Race/Ethnicity, Customized Black or African American | 80 Participants | 46 Participants | 126 Participants |
| Race/Ethnicity, Customized Multiple | 12 Participants | 6 Participants | 18 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 14 Participants | 8 Participants | 22 Participants |
| Race/Ethnicity, Customized White | 261 Participants | 129 Participants | 390 Participants |
| Randomization validated Investigator's Global Assessment Scale for Atopic Dermatitis (vIGA-AD) 2 - Mild | 105 Participants | 57 Participants | 162 Participants |
| Randomization validated Investigator's Global Assessment Scale for Atopic Dermatitis (vIGA-AD) 3 - Moderate | 328 Participants | 164 Participants | 492 Participants |
| Sex: Female, Male Female | 237 Participants | 129 Participants | 366 Participants |
| Sex: Female, Male Male | 196 Participants | 92 Participants | 288 Participants |
| Verified vIGA-AD Mild | 103 Participants | 59 Participants | 162 Participants |
| Verified vIGA-AD Moderate | 330 Participants | 162 Participants | 492 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 433 | 0 / 221 |
| other Total, other adverse events | 0 / 433 | 0 / 221 |
| serious Total, serious adverse events | 4 / 433 | 0 / 221 |
Outcome results
Primary
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.
Time frame: Week 4
Population: All randomized participants are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.15% | Achievement of Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Success at Week 4 | 32.0 percentage of participants |
| Vehicle Cream | Achievement of Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Success at Week 4 | 15.2 percentage of participants |
Comparison: Difference in vIGA-AD Success at Week 4p-value: <0.000195% CI: [1.881, 4.647]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Week 4
Population: All randomized participants are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.15% | Achievement of ≥ 75% Reduction in the Eczema Area and Severity Index (EASI-75) at Week 4 | 43.2 percentage of participants |
| Vehicle Cream | Achievement of ≥ 75% Reduction in the Eczema Area and Severity Index (EASI-75) at Week 4 | 22.0 percentage of participants |
Comparison: EASI-75 at Week 4p-value: <0.000195% CI: [2.102, 4.795]Cochran-Mantel-Haenszel
Secondary
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).
Time frame: Week 1
Population: All randomized participants ≥12 years of age with a baseline WI-NRS ≥4 are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.15% | 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 | 9.5 percentage of participants |
| Vehicle Cream | 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 | 2.3 percentage of participants |
Comparison: WI-NRS Success at Week 1p-value: 0.015995% CI: [1.161, 12.511]Cochran-Mantel-Haenszel
Secondary
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).
Time frame: Week 2
Population: All randomized participants ≥12 years of age with a baseline WI-NRS ≥4 are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.15% | 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 | 23.8 percentage of participants |
| Vehicle Cream | 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 | 9.8 percentage of participants |
Comparison: WI-NRS Success at Week 2p-value: 0.001695% CI: [1.45, 5.457]Cochran-Mantel-Haenszel
Secondary
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).
Time frame: Week 4
Population: All randomized participants ≥12 years of age with a baseline WI-NRS ≥4 are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.15% | 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 | 33.6 percentage of participants |
| Vehicle Cream | 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 | 20.7 percentage of participants |
Comparison: WI-NRS Success at Week 4p-value: 0.008995% CI: [1.186, 3.319]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Week 1
Population: All randomized participants are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.15% | Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 1 | 14.3 percentage of participants |
| Vehicle Cream | Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 1 | 5.9 percentage of participants |
Comparison: vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 1p-value: 0.000295% CI: [1.705, 7.007]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Week 2
Population: All randomized participants are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.15% | Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 2 | 31.8 percentage of participants |
| Vehicle Cream | Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 2 | 13.6 percentage of participants |
Comparison: vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 2p-value: <0.000195% CI: [2.217, 5.911]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Week 4
Population: All randomized participants are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.15% | Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 4 | 41.5 percentage of participants |
| Vehicle Cream | Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 4 | 25.2 percentage of participants |
Comparison: vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 4p-value: <0.000195% CI: [1.707, 3.843]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Week 1
Population: All randomized participants are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.15% | Achievement of vIGA-AD Success at Week 1 | 8.1 percentage of participants |
| Vehicle Cream | Achievement of vIGA-AD Success at Week 1 | 0.5 percentage of participants |
Comparison: vIGA-AD Success at Week 1p-value: <0.000195% CI: [2.815, 229.388]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Week 2
Population: All randomized participants are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.15% | Achievement of vIGA-AD Success at Week 2 | 21.2 percentage of participants |
| Vehicle Cream | Achievement of vIGA-AD Success at Week 2 | 6.4 percentage of participants |
Comparison: vIGA-AD Success at Week 2p-value: <0.000195% CI: [2.31, 7.926]Cochran-Mantel-Haenszel
Secondary
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.
Time frame: Week 4
Population: All randomized participants who were included in the moderate baseline vIGA-AD group during randomization are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.15% | Achievement of vIGA-AD Success at Week 4 in Participants With Moderate Baseline Scores | 35.0 percentage of participants |
| Vehicle Cream | Achievement of vIGA-AD Success at Week 4 in Participants With Moderate Baseline Scores | 17.5 percentage of participants |
Comparison: Difference in vIGA-AD Success at Week 4p-value: <0.000195% CI: [1.64, 4.359]Cochran-Mantel-Haenszel