Atopic Dermatitis Eczema
Conditions
Brief summary
This was a Phase 3, 4-week, double-blind study to assess the safety and efficacy of ARQ-151 cream compared to vehicle cream applied once daily (qd) for 4 weeks in children 2 to 5 years of age with atopic dermatitis (AD).
Interventions
Roflumilast cream for topical application.
DRUGVehicle Cream
Vehicle cream matched to roflumilast cream for topical application.
Sponsors
Arcutis Biotherapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 5 Years
Healthy volunteers
No
Inclusion criteria
1. Informed consent by parent(s) or legal guardian as required by local laws. 2. Males and females, ages 2 to 5 years old at time of signing Informed Consent (Screening) and at Baseline (Day 1). 3. Diagnosed with atopic dermatitis for at least 6 weeks, as determined by the Investigator. Stable disease for the past 4 weeks with no significant flares in atopic dermatitis before screening. 4. In good health as judged by the Investigator. 5. 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 for 4 weeks prior to Baseline/Day 1 and during the study. 4. Previous treatment with ARQ-151. 5. 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. 6. Subjects who are family members of the clinical study site, clinical study staff, or sponsor, or family members of enrolled (in other studies of ARQ-151) 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 with vIGA-AD success at Week 4 is presented. The vIGA-AD is a static evaluation of qualitative overall AD severity with five severity grades (reported as score of 0 'clear' to 4 'severe' with higher scores indicating greater symptom severity. vIGA success was defined as score of 'clear' or 'almost clear' plus a 2-grade improvement from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Achievement of 75% Reduction in the Eczema Area and Severity Index (EASI-75) at Week 4 In Participants With 'Moderate' Baseline vIGA | Week 4 | The percentage of participants with a moderate baseline vIGA-AD score who achieved EASI-75 is presented. 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'). 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. |
| Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' | Week 4 | The percentage of participants with vIGA-AD score of 'clear' or 'almost clear' at Week 4 is presented. The vIGA is a static evaluation of qualitative overall AD severity with five severity grades (reported as score of 0 'clear' to 4 'severe' with higher scores indicating greater symptom severity. |
| Achievement of vIGA-AD Success at Week 2 | Week 2 | The percentage of participants with vIGA-AD success at Week 2 is presented. The vIGA-AD is a static evaluation of qualitative overall AD severity with five severity grades (reported as score of 0 'clear' to 4 'severe' with higher scores indicating greater symptom severity. vIGA success was defined as score of 'clear' or 'almost clear' plus a 2-grade improvement from baseline. |
| Achievement of vIGA-AD Success at Week 4 in Participants With 'Moderate' Baseline vIGA-AD | Week 4 | The percentage of participants with vIGA-AD success at Week 4 who had 'moderate' vIGA-AD score (vIGA score of 3) at baseline is presented. The vIGA-AD is a static evaluation of qualitative overall AD severity with five severity grades (reported as score of 0 'clear' to 4 'severe' with higher scores indicating greater symptom severity. vIGA-AD success was defined as score of 'clear' or 'almost clear' plus a 2-grade improvement from baseline in participants with moderate vIGA-AD baseline. |
| Achievement of vIGA-AD of 'Clear' or 'Almost Clear' at Week 2 | Week 2 | The percentage of participants with vIGA-AD score of 'clear' or 'almost clear' at Week 2 is presented. The vIGA-AD is a static evaluation of qualitative overall AD severity with five severity grades (reported as score of 0 'clear' to 4 'severe' with higher scores indicating greater symptom severity. |
| Achievement of vIGA-AD of 'Clear' or 'Almost Clear' at Week 1 | Week 1 | The percentage of participants with vIGA-AD score of 'clear' or 'almost clear' at Week 1 is presented. The vIGA-AD is a static evaluation of qualitative overall AD severity with five severity grades (reported as score of 0 'clear' to 4 'severe' with higher scores indicating greater symptom severity. |
| Achievement of vIGA-AD Success at Week 1 | Week 1 | The percentage of participants with vIGA-AD success at Week 1 is presented. The vIGA-AD is a static evaluation of qualitative overall AD severity with five severity grades (reported as score of 0 'clear' to 4 'severe' with higher scores indicating greater symptom severity. vIGA-AD success was defined as score of 'clear' or 'almost clear' plus a 2-grade improvement from baseline. |
Countries
Canada, United States
Participant flow
Pre-assignment details
This study was conducted at 109 centers in the United States, Canada, and Poland.
Participants by arm
| Arm | Count |
|---|---|
| Roflumilast Cream 0.05% Participants applied roflumilast cream 0.05% qd for 4 weeks. | 437 |
| Vehicle Cream Participants applied vehicle cream qd for 4 weeks. | 215 |
| Total | 652 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 4 |
| Overall Study | Lack of Efficacy | 4 | 4 |
| Overall Study | Lost to Follow-up | 5 | 4 |
| Overall Study | Physician Decision | 2 | 1 |
| Overall Study | Withdrawal by Subject | 11 | 10 |
Baseline characteristics
| Characteristic | Vehicle Cream | Total | Roflumilast Cream 0.05% |
|---|---|---|---|
| Age, Continuous | 3.2 years STANDARD_DEVIATION 1.1 | 3.3 years STANDARD_DEVIATION 1.09 | 3.3 years STANDARD_DEVIATION 1.09 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 31 Participants | 113 Participants | 82 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 184 Participants | 536 Participants | 352 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 17 Participants | 54 Participants | 37 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants | 100 Participants | 68 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 32 Participants | 28 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 12 Participants | 8 Participants |
| Race (NIH/OMB) White | 156 Participants | 451 Participants | 295 Participants |
| Sex: Female, Male Female | 99 Participants | 310 Participants | 211 Participants |
| Sex: Female, Male Male | 116 Participants | 342 Participants | 226 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 437 | 0 / 215 |
| other Total, other adverse events | 0 / 437 | 0 / 215 |
| serious Total, serious adverse events | 1 / 437 | 0 / 215 |
Outcome results
Primary
Achievement of Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Success at Week 4
The percentage of participants with vIGA-AD success at Week 4 is presented. The vIGA-AD is a static evaluation of qualitative overall AD severity with five severity grades (reported as score of 0 'clear' to 4 'severe' with higher scores indicating greater symptom severity. vIGA success was defined as score of 'clear' or 'almost clear' plus a 2-grade improvement from baseline.
Time frame: Week 4
Population: All randomized participants are included, 1 participant in the Roflumilast Cream 0.05% arm was inadvertently treated prior to randomization and thus excluded from analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.05% | Achievement of Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Success at Week 4 | 25.4 percentage of participants |
| Vehicle Cream | Achievement of Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Success at Week 4 | 10.7 percentage of participants |
Comparison: vIGA Success at Week 4p-value: <0.000197.5% CI: [1.648, 5.064]Cochran-Mantel-Haenszel
Secondary
Achievement of 75% Reduction in the Eczema Area and Severity Index (EASI-75) at Week 4 In Participants With 'Moderate' Baseline vIGA
The percentage of participants with a moderate baseline vIGA-AD score who achieved EASI-75 is presented. 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'). 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.
Time frame: Week 4
Population: All randomized participants are included, with the exception of 1 participant in the Roflumilast Cream 0.05% arm who was inadvertently treated prior to randomization and thus excluded from analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.05% | Achievement of 75% Reduction in the Eczema Area and Severity Index (EASI-75) at Week 4 In Participants With 'Moderate' Baseline vIGA | 39.4 percentage of participants |
| Vehicle Cream | Achievement of 75% Reduction in the Eczema Area and Severity Index (EASI-75) at Week 4 In Participants With 'Moderate' Baseline vIGA | 20.6 percentage of participants |
Comparison: EASI-75 at Week 4p-value: <0.000197.5% CI: [1.578, 3.87]Cochran-Mantel-Haenszel
Secondary
Achievement of vIGA-AD of 'Clear' or 'Almost Clear' at Week 1
The percentage of participants with vIGA-AD score of 'clear' or 'almost clear' at Week 1 is presented. The vIGA-AD is a static evaluation of qualitative overall AD severity with five severity grades (reported as score of 0 'clear' to 4 'severe' with higher scores indicating greater symptom severity.
Time frame: Week 1
Population: All randomized participants are included, 1 participant in the Roflumilast Cream 0.05% arm was inadvertently treated prior to randomization and thus excluded from analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.05% | Achievement of vIGA-AD of 'Clear' or 'Almost Clear' at Week 1 | 17.00 percentage of participants |
| Vehicle Cream | Achievement of vIGA-AD of 'Clear' or 'Almost Clear' at Week 1 | 3.7 percentage of participants |
Comparison: vIGA-AD of Clear or Almost Clear at Week 2p-value: <0.000197.5% CI: [2.342, 14.113]Cochran-Mantel-Haenszel
Secondary
Achievement of vIGA-AD of 'Clear' or 'Almost Clear' at Week 2
The percentage of participants with vIGA-AD score of 'clear' or 'almost clear' at Week 2 is presented. The vIGA-AD is a static evaluation of qualitative overall AD severity with five severity grades (reported as score of 0 'clear' to 4 'severe' with higher scores indicating greater symptom severity.
Time frame: Week 2
Population: All randomized participants are included, 1 participant in the Roflumilast Cream 0.05% arm was inadvertently treated prior to randomization and thus excluded from analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.05% | Achievement of vIGA-AD of 'Clear' or 'Almost Clear' at Week 2 | 30.4 percentage of participants |
| Vehicle Cream | Achievement of vIGA-AD of 'Clear' or 'Almost Clear' at Week 2 | 10.6 percentage of participants |
Comparison: vIGA-AD of Clear or Almost Clear at Week 2p-value: <0.000197.5% CI: [2.137, 6.761]Cochran-Mantel-Haenszel
Secondary
Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear'
The percentage of participants with vIGA-AD score of 'clear' or 'almost clear' at Week 4 is presented. The vIGA is a static evaluation of qualitative overall AD severity with five severity grades (reported as score of 0 'clear' to 4 'severe' with higher scores indicating greater symptom severity.
Time frame: Week 4
Population: All randomized participants are included, 1 participant in the Roflumilast Cream 0.05% arm was inadvertently treated prior to randomization and thus excluded from analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.05% | Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' | 35.4 percentage of participants |
| Vehicle Cream | Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' | 14.6 percentage of participants |
Comparison: vIGA Score of 'Clear' or 'Almost Clear' at Week 4p-value: <0.000197.5% CI: [1.98, 5.475]Cochran-Mantel-Haenszel
Secondary
Achievement of vIGA-AD Success at Week 1
The percentage of participants with vIGA-AD success at Week 1 is presented. The vIGA-AD is a static evaluation of qualitative overall AD severity with five severity grades (reported as score of 0 'clear' to 4 'severe' with higher scores indicating greater symptom severity. vIGA-AD success was defined as score of 'clear' or 'almost clear' plus a 2-grade improvement from baseline.
Time frame: Week 1
Population: All randomized participants are included, 1 participant in the Roflumilast Cream 0.05% arm was inadvertently treated prior to randomization and thus excluded from analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.05% | Achievement of vIGA-AD Success at Week 1 | 9.4 percentage of participants |
| Vehicle Cream | Achievement of vIGA-AD Success at Week 1 | 0.9 percentage of participants |
Comparison: vIGA-AD Success at Week 1p-value: <0.000197.5% CI: [2.216, 59.101]Cochran-Mantel-Haenszel
Secondary
Achievement of vIGA-AD Success at Week 2
The percentage of participants with vIGA-AD success at Week 2 is presented. The vIGA-AD is a static evaluation of qualitative overall AD severity with five severity grades (reported as score of 0 'clear' to 4 'severe' with higher scores indicating greater symptom severity. vIGA success was defined as score of 'clear' or 'almost clear' plus a 2-grade improvement from baseline.
Time frame: Week 2
Population: All randomized participants are included, 1 participant in the Roflumilast Cream 0.05% arm was inadvertently treated prior to randomization and thus excluded from analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.05% | Achievement of vIGA-AD Success at Week 2 | 21.2 percentage of participants |
| Vehicle Cream | Achievement of vIGA-AD Success at Week 2 | 6.8 percentage of participants |
p-value: <0.000197.5% CI: [1.912, 7.313]Cochran-Mantel-Haenszel
Secondary
Achievement of vIGA-AD Success at Week 4 in Participants With 'Moderate' Baseline vIGA-AD
The percentage of participants with vIGA-AD success at Week 4 who had 'moderate' vIGA-AD score (vIGA score of 3) at baseline is presented. The vIGA-AD is a static evaluation of qualitative overall AD severity with five severity grades (reported as score of 0 'clear' to 4 'severe' with higher scores indicating greater symptom severity. vIGA-AD success was defined as score of 'clear' or 'almost clear' plus a 2-grade improvement from baseline in participants with moderate vIGA-AD baseline.
Time frame: Week 4
Population: All randomized participants with a baseline vIGA score of 'moderate' are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Roflumilast Cream 0.05% | Achievement of vIGA-AD Success at Week 4 in Participants With 'Moderate' Baseline vIGA-AD | 27.7 percentage of participants |
| Vehicle Cream | Achievement of vIGA-AD Success at Week 4 in Participants With 'Moderate' Baseline vIGA-AD | 11.0 percentage of participants |
Comparison: vIGA Success at Week 4 in Participants with Moderate Baseline vIGAp-value: <0.000197.5% CI: [1.662, 5.772]Chi-squared