Trial Outcomes & Findings for Trial of PDE4 Inhibition With Roflumilast for the Management of Atopic Dermatitis (NCT NCT04773587)
NCT ID: NCT04773587
Last Updated: 2024-10-09
Results Overview
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.
COMPLETED
PHASE3
654 participants
Week 4
2024-10-09
Participant Flow
This study was conducted at 65 centers in the United States, Canada, and Poland.
Participant milestones
| Measure |
Roflumilast Cream 0.15%
Participants with mild to moderate AD applied roflumilast cream 0.15% once daily (QD) for 4 weeks.
|
Vehicle Cream
Participants with mild to moderate AD applied vehicle cream QD for 4 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
433
|
221
|
|
Overall Study
COMPLETED
|
404
|
208
|
|
Overall Study
NOT COMPLETED
|
29
|
13
|
Reasons for withdrawal
| Measure |
Roflumilast Cream 0.15%
Participants with mild to moderate AD applied roflumilast cream 0.15% once daily (QD) for 4 weeks.
|
Vehicle Cream
Participants with mild to moderate AD applied vehicle cream QD for 4 weeks.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
11
|
3
|
|
Overall Study
Adverse Event
|
6
|
3
|
|
Overall Study
Lack of Efficacy
|
5
|
2
|
|
Overall Study
Withdrawal by Subject
|
4
|
5
|
|
Overall Study
Noncompliance
|
1
|
0
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Consent withdrawn due to AEs of nausea, headaches, dizziness, and brain fog
|
1
|
0
|
Baseline Characteristics
Trial of PDE4 Inhibition With Roflumilast for the Management of Atopic Dermatitis
Baseline characteristics by cohort
| Measure |
Roflumilast Cream 0.15%
n=433 Participants
Participants with mild to moderate AD applied roflumilast cream 0.15% once daily (QD) for 4 weeks.
|
Vehicle Cream
n=221 Participants
Participants with mild to moderate AD applied vehicle cream QD for 4 weeks.
|
Total
n=654 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
28.1 years
STANDARD_DEVIATION 19.14 • n=99 Participants
|
28.5 years
STANDARD_DEVIATION 18.94 • n=107 Participants
|
28.2 years
STANDARD_DEVIATION 19.06 • n=206 Participants
|
|
Sex: Female, Male
Female
|
237 Participants
n=99 Participants
|
129 Participants
n=107 Participants
|
366 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
196 Participants
n=99 Participants
|
92 Participants
n=107 Participants
|
288 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
99 Participants
n=99 Participants
|
56 Participants
n=107 Participants
|
155 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
333 Participants
n=99 Participants
|
164 Participants
n=107 Participants
|
497 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White
|
261 Participants
n=99 Participants
|
129 Participants
n=107 Participants
|
390 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska native
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Asian
|
63 Participants
n=99 Participants
|
32 Participants
n=107 Participants
|
95 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or other Pacific Islander
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
80 Participants
n=99 Participants
|
46 Participants
n=107 Participants
|
126 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
12 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Other
|
14 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
22 Participants
n=206 Participants
|
|
Randomization validated Investigator's Global Assessment Scale for Atopic Dermatitis (vIGA-AD)
2 - Mild
|
105 Participants
n=99 Participants
|
57 Participants
n=107 Participants
|
162 Participants
n=206 Participants
|
|
Randomization validated Investigator's Global Assessment Scale for Atopic Dermatitis (vIGA-AD)
3 - Moderate
|
328 Participants
n=99 Participants
|
164 Participants
n=107 Participants
|
492 Participants
n=206 Participants
|
|
Verified vIGA-AD
Mild
|
103 Participants
n=99 Participants
|
59 Participants
n=107 Participants
|
162 Participants
n=206 Participants
|
|
Verified vIGA-AD
Moderate
|
330 Participants
n=99 Participants
|
162 Participants
n=107 Participants
|
492 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Week 4Population: All randomized participants are included.
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.
Outcome measures
| Measure |
Roflumilast Cream 0.15%
n=433 Participants
Participants with mild to moderate AD applied roflumilast cream 0.15% once daily (QD) for 4 weeks.
|
Vehicle Cream
n=221 Participants
Participants with mild to moderate AD applied vehicle cream QD for 4 weeks.
|
|---|---|---|
|
Achievement of Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Success at Week 4
|
32.0 percentage of participants
Interval 27.79 to 36.63
|
15.2 percentage of participants
Interval 11.06 to 20.64
|
SECONDARY outcome
Timeframe: Week 4Population: All randomized participants who were included in the "moderate" baseline vIGA-AD group during randomization are included.
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.
Outcome measures
| Measure |
Roflumilast Cream 0.15%
n=328 Participants
Participants with mild to moderate AD applied roflumilast cream 0.15% once daily (QD) for 4 weeks.
|
Vehicle Cream
n=164 Participants
Participants with mild to moderate AD applied vehicle cream QD for 4 weeks.
|
|---|---|---|
|
Achievement of vIGA-AD Success at Week 4 in Participants With "Moderate" Baseline Scores
|
35.0 percentage of participants
Interval 29.97 to 40.36
|
17.5 percentage of participants
Interval 12.38 to 24.13
|
SECONDARY outcome
Timeframe: Week 4Population: All randomized participants ≥12 years of age with a baseline WI-NRS ≥4 are included.
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).
Outcome measures
| Measure |
Roflumilast Cream 0.15%
n=278 Participants
Participants with mild to moderate AD applied roflumilast cream 0.15% once daily (QD) for 4 weeks.
|
Vehicle Cream
n=135 Participants
Participants with mild to moderate AD applied vehicle cream QD for 4 weeks.
|
|---|---|---|
|
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
Interval 28.19 to 39.41
|
20.7 percentage of participants
Interval 14.61 to 28.58
|
SECONDARY outcome
Timeframe: Week 2Population: All randomized participants ≥12 years of age with a baseline WI-NRS ≥4 are included.
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).
Outcome measures
| Measure |
Roflumilast Cream 0.15%
n=278 Participants
Participants with mild to moderate AD applied roflumilast cream 0.15% once daily (QD) for 4 weeks.
|
Vehicle Cream
n=135 Participants
Participants with mild to moderate AD applied vehicle cream QD for 4 weeks.
|
|---|---|---|
|
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
Interval 19.14 to 29.24
|
9.8 percentage of participants
Interval 5.79 to 16.03
|
SECONDARY outcome
Timeframe: Week 1Population: All randomized participants ≥12 years of age with a baseline WI-NRS ≥4 are included.
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).
Outcome measures
| Measure |
Roflumilast Cream 0.15%
n=278 Participants
Participants with mild to moderate AD applied roflumilast cream 0.15% once daily (QD) for 4 weeks.
|
Vehicle Cream
n=135 Participants
Participants with mild to moderate AD applied vehicle cream QD for 4 weeks.
|
|---|---|---|
|
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
Interval 6.6 to 13.6
|
2.3 percentage of participants
Interval 0.77 to 6.41
|
SECONDARY outcome
Timeframe: Week 4Population: All randomized participants are included.
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.
Outcome measures
| Measure |
Roflumilast Cream 0.15%
n=433 Participants
Participants with mild to moderate AD applied roflumilast cream 0.15% once daily (QD) for 4 weeks.
|
Vehicle Cream
n=221 Participants
Participants with mild to moderate AD applied vehicle cream QD for 4 weeks.
|
|---|---|---|
|
Achievement of ≥ 75% Reduction in the Eczema Area and Severity Index (EASI-75) at Week 4
|
43.2 percentage of participants
Interval 38.54 to 47.94
|
22.0 percentage of participants
Interval 16.97 to 28.04
|
SECONDARY outcome
Timeframe: Week 4Population: All randomized participants are included.
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.
Outcome measures
| Measure |
Roflumilast Cream 0.15%
n=433 Participants
Participants with mild to moderate AD applied roflumilast cream 0.15% once daily (QD) for 4 weeks.
|
Vehicle Cream
n=221 Participants
Participants with mild to moderate AD applied vehicle cream QD for 4 weeks.
|
|---|---|---|
|
Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 4
|
41.5 percentage of participants
Interval 36.93 to 46.25
|
25.2 percentage of participants
Interval 19.91 to 31.41
|
SECONDARY outcome
Timeframe: Week 2Population: All randomized participants are included.
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.
Outcome measures
| Measure |
Roflumilast Cream 0.15%
n=433 Participants
Participants with mild to moderate AD applied roflumilast cream 0.15% once daily (QD) for 4 weeks.
|
Vehicle Cream
n=221 Participants
Participants with mild to moderate AD applied vehicle cream QD for 4 weeks.
|
|---|---|---|
|
Achievement of vIGA-AD Success at Week 2
|
21.2 percentage of participants
Interval 17.57 to 25.33
|
6.4 percentage of participants
Interval 3.84 to 10.44
|
SECONDARY outcome
Timeframe: Week 1Population: All randomized participants are included.
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.
Outcome measures
| Measure |
Roflumilast Cream 0.15%
n=433 Participants
Participants with mild to moderate AD applied roflumilast cream 0.15% once daily (QD) for 4 weeks.
|
Vehicle Cream
n=221 Participants
Participants with mild to moderate AD applied vehicle cream QD for 4 weeks.
|
|---|---|---|
|
Achievement of vIGA-AD Success at Week 1
|
8.1 percentage of participants
Interval 5.87 to 11.03
|
0.5 percentage of participants
Interval 0.08 to 2.52
|
SECONDARY outcome
Timeframe: Week 2Population: All randomized participants are included.
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.
Outcome measures
| Measure |
Roflumilast Cream 0.15%
n=433 Participants
Participants with mild to moderate AD applied roflumilast cream 0.15% once daily (QD) for 4 weeks.
|
Vehicle Cream
n=221 Participants
Participants with mild to moderate AD applied vehicle cream QD for 4 weeks.
|
|---|---|---|
|
Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 2
|
31.8 percentage of participants
Interval 27.58 to 36.38
|
13.6 percentage of participants
Interval 9.72 to 18.79
|
SECONDARY outcome
Timeframe: Week 1Population: All randomized participants are included.
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.
Outcome measures
| Measure |
Roflumilast Cream 0.15%
n=433 Participants
Participants with mild to moderate AD applied roflumilast cream 0.15% once daily (QD) for 4 weeks.
|
Vehicle Cream
n=221 Participants
Participants with mild to moderate AD applied vehicle cream QD for 4 weeks.
|
|---|---|---|
|
Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 1
|
14.3 percentage of participants
Interval 11.33 to 17.93
|
5.9 percentage of participants
Interval 3.47 to 9.8
|
Adverse Events
Roflumilast Cream 0.15%
Vehicle Cream
Serious adverse events
| Measure |
Roflumilast Cream 0.15%
n=433 participants at risk
Participants with mild to moderate AD applied roflumilast cream 0.15% once daily (QD) for 4 weeks.
|
Vehicle Cream
n=221 participants at risk
Participants with mild to moderate AD applied vehicle cream QD for 4 weeks.
|
|---|---|---|
|
Infections and infestations
Diverticulitis
|
0.23%
1/433 • Up to approximately 29 days
|
0.00%
0/221 • Up to approximately 29 days
|
|
Psychiatric disorders
Depression
|
0.23%
1/433 • Up to approximately 29 days
|
0.00%
0/221 • Up to approximately 29 days
|
|
Psychiatric disorders
Suicidal ideation
|
0.23%
1/433 • Up to approximately 29 days
|
0.00%
0/221 • Up to approximately 29 days
|
|
Vascular disorders
Pulmonary embolism
|
0.23%
1/433 • Up to approximately 29 days
|
0.00%
0/221 • Up to approximately 29 days
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor is generally supportive of publication of trial results.
- Publication restrictions are in place
Restriction type: OTHER