Trial Outcomes & Findings for Trial of PDE4 Inhibition With Roflumilast for the Management of Atopic Dermatitis (INTEGUMENT-II) (NCT NCT04773600)
NCT ID: NCT04773600
Last Updated: 2024-10-04
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
683 participants
Week 4
2024-10-04
Participant Flow
Participant milestones
| Measure |
Roflumilast Cream 0.15%
Participants applied roflumilast cream 0.15% qd for 4 weeks.
|
Vehicle Cream
Participants applied vehicle cream qd for 4 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
451
|
232
|
|
Overall Study
COMPLETED
|
410
|
211
|
|
Overall Study
NOT COMPLETED
|
41
|
21
|
Reasons for withdrawal
| Measure |
Roflumilast Cream 0.15%
Participants applied roflumilast cream 0.15% qd for 4 weeks.
|
Vehicle Cream
Participants applied vehicle cream qd for 4 weeks.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
15
|
9
|
|
Overall Study
Lost to Follow-up
|
10
|
6
|
|
Overall Study
Adverse Event
|
8
|
2
|
|
Overall Study
Lack of Efficacy
|
2
|
3
|
|
Overall Study
Noncompliance
|
2
|
0
|
|
Overall Study
Protocol Violation
|
2
|
0
|
|
Overall Study
Physician Decision
|
0
|
1
|
|
Overall Study
Caregiver Elected Other Therapy
|
1
|
0
|
|
Overall Study
Emergency Travel Out of Country
|
1
|
0
|
Baseline Characteristics
Trial of PDE4 Inhibition With Roflumilast for the Management of Atopic Dermatitis (INTEGUMENT-II)
Baseline characteristics by cohort
| Measure |
Roflumilast Cream 0.15%
n=451 Participants
Participants applied roflumilast cream 0.15% qd for 4 weeks.
|
Vehicle Cream
n=232 Participants
Participants applied vehicle cream qd for 4 weeks.
|
Total
n=683 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
27.7 years
STANDARD_DEVIATION 19.60 • n=99 Participants
|
26.2 years
STANDARD_DEVIATION 18.94 • n=107 Participants
|
27.2 years
STANDARD_DEVIATION 19.38 • n=206 Participants
|
|
Sex: Female, Male
Female
|
252 Participants
n=99 Participants
|
143 Participants
n=107 Participants
|
395 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
199 Participants
n=99 Participants
|
89 Participants
n=107 Participants
|
288 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
51 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
67 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
397 Participants
n=99 Participants
|
213 Participants
n=107 Participants
|
610 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White
|
268 Participants
n=99 Participants
|
138 Participants
n=107 Participants
|
406 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Black or African-American
|
96 Participants
n=99 Participants
|
50 Participants
n=107 Participants
|
146 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Asian
|
51 Participants
n=99 Participants
|
30 Participants
n=107 Participants
|
81 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
American-Indian or Alaska Native
|
5 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
12 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Other
|
19 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
24 Participants
n=206 Participants
|
|
Randomization validated Investigator Global Assessment for Atopic Dermatitis (vIGA) Baseline Score
Mild
|
109 Participants
n=99 Participants
|
53 Participants
n=107 Participants
|
162 Participants
n=206 Participants
|
|
Randomization validated Investigator Global Assessment for Atopic Dermatitis (vIGA) Baseline Score
Moderate
|
342 Participants
n=99 Participants
|
179 Participants
n=107 Participants
|
521 Participants
n=206 Participants
|
|
Investigator-Verified vIGA Baseline Score
Mild
|
108 Participants
n=99 Participants
|
53 Participants
n=107 Participants
|
161 Participants
n=206 Participants
|
|
Investigator-Verified vIGA Baseline Score
Moderate
|
343 Participants
n=99 Participants
|
179 Participants
n=107 Participants
|
522 Participants
n=206 Participants
|
|
WI-NRS Baseline Score ≥4
≥4
|
359 Participants
n=99 Participants
|
181 Participants
n=107 Participants
|
540 Participants
n=206 Participants
|
|
WI-NRS Baseline Score ≥4
≤3
|
92 Participants
n=99 Participants
|
51 Participants
n=107 Participants
|
143 Participants
n=206 Participants
|
|
Baseline Eczema Area and Severity Index (EASI) Score
|
8.50 units on a scale
n=99 Participants
|
8.4 units on a scale
n=107 Participants
|
8.50 units on a scale
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=451 Participants
Participants applied roflumilast cream 0.15% qd for 4 weeks.
|
Vehicle Cream
n=232 Participants
Participants applied vehicle cream qd for 4 weeks.
|
|---|---|---|
|
Achievement of Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Success at Week 4
|
28.9 percentage of participants
|
12.0 percentage of participants
|
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=342 Participants
Participants applied roflumilast cream 0.15% qd for 4 weeks.
|
Vehicle Cream
n=179 Participants
Participants applied vehicle cream qd for 4 weeks.
|
|---|---|---|
|
Achievement of vIGA-AD Success at Week 4 in Participants With "Moderate" Baseline Scores
|
32.9 percentage of participants
|
13.1 percentage of participants
|
SECONDARY outcome
Timeframe: Week 2Population: 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=451 Participants
Participants applied roflumilast cream 0.15% qd for 4 weeks.
|
Vehicle Cream
n=232 Participants
Participants applied vehicle cream qd for 4 weeks.
|
|---|---|---|
|
vIGA-AD Success at Week 2
|
17.7 percentage of participants
|
5.3 percentage of participants
|
SECONDARY outcome
Timeframe: Week 1Population: 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=451 Participants
Participants applied roflumilast cream 0.15% qd for 4 weeks.
|
Vehicle Cream
n=232 Participants
Participants applied vehicle cream qd for 4 weeks.
|
|---|---|---|
|
vIGA-AD Success at Week 1
|
5.9 percentage of participants
|
3.1 percentage of participants
|
SECONDARY outcome
Timeframe: Week 4Population: All randomized participants who were ≥12 years of age, had an average weekly WI-NRS pruritus score ≥4 at baseline, and completed at least 4 of 7 evaluable daily WI-NRS questionnaires during the last 7 days of the Screening period are included. Multiple imputation was used to handle missing cases.
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).
Outcome measures
| Measure |
Roflumilast Cream 0.15%
n=264 Participants
Participants applied roflumilast cream 0.15% qd for 4 weeks.
|
Vehicle Cream
n=136 Participants
Participants applied vehicle cream qd for 4 weeks.
|
|---|---|---|
|
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
|
30.2 percentage of participants
Interval 24.77 to 36.31
|
12.4 percentage of participants
Interval 7.77 to 19.26
|
SECONDARY outcome
Timeframe: Week 2Population: All randomized participants who were ≥12 years of age, had an average weekly WI-NRS pruritus score ≥4 at baseline, and completed at least 4 of 7 evaluable daily WI-NRS questionnaires during the last 7 days of the Screening period are included. Multiple imputation was used to handle missing cases.
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).
Outcome measures
| Measure |
Roflumilast Cream 0.15%
n=264 Participants
Participants applied roflumilast cream 0.15% qd for 4 weeks.
|
Vehicle Cream
n=136 Participants
Participants applied vehicle cream qd for 4 weeks.
|
|---|---|---|
|
Achievement of a 4-point Reduction at Week 2 in the WI-NRS in Participants With Baseline WI-NRS Score ≥4
|
22.3 percentage of participants
Interval 17.66 to 27.82
|
6.9 percentage of participants
Interval 3.66 to 12.56
|
SECONDARY outcome
Timeframe: Week 1Population: All randomized participants who were ≥12 years of age, had an average weekly WI-NRS pruritus score ≥4 at baseline, and completed at least 4 of 7 evaluable daily WI-NRS questionnaires during the last 7 days of the Screening period are included. Multiple imputation was used to handle missing cases.
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).
Outcome measures
| Measure |
Roflumilast Cream 0.15%
n=264 Participants
Participants applied roflumilast cream 0.15% qd for 4 weeks.
|
Vehicle Cream
n=136 Participants
Participants applied vehicle cream qd for 4 weeks.
|
|---|---|---|
|
Achievement of a 4-point Reduction at Week 1 in the WI-NRS in Participants With Baseline WI-NRS Score ≥4
|
11.2 percentage of participants
Interval 7.89 to 15.57
|
1.6 percentage of participants
Interval 0.44 to 5.58
|
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=451 Participants
Participants applied roflumilast cream 0.15% qd for 4 weeks.
|
Vehicle Cream
n=232 Participants
Participants applied vehicle cream qd for 4 weeks.
|
|---|---|---|
|
Achievement of ≥75% Decrease From Baseline at Week 4 in the Eczema Area and Severity Index (EASI-75)
|
42.0 percentage of participants
Interval 37.45 to 46.72
|
19.7 percentage of participants
Interval 15.04 to 25.44
|
SECONDARY outcome
Timeframe: Week 4Population: All randomized participants are included.
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.
Outcome measures
| Measure |
Roflumilast Cream 0.15%
n=451 Participants
Participants applied roflumilast cream 0.15% qd for 4 weeks.
|
Vehicle Cream
n=232 Participants
Participants applied vehicle cream qd for 4 weeks.
|
|---|---|---|
|
Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 4
|
39.0 percentage of participants
|
16.9 percentage of participants
|
SECONDARY outcome
Timeframe: Week 2Population: All randomized participants are included.
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.
Outcome measures
| Measure |
Roflumilast Cream 0.15%
n=451 Participants
Participants applied roflumilast cream 0.15% qd for 4 weeks.
|
Vehicle Cream
n=232 Participants
Participants applied vehicle cream qd for 4 weeks.
|
|---|---|---|
|
Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 2
|
27.6 percentage of participants
|
10.7 percentage of participants
|
SECONDARY outcome
Timeframe: Week 1Population: All randomized participants are included.
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.
Outcome measures
| Measure |
Roflumilast Cream 0.15%
n=451 Participants
Participants applied roflumilast cream 0.15% qd for 4 weeks.
|
Vehicle Cream
n=232 Participants
Participants applied vehicle cream qd for 4 weeks.
|
|---|---|---|
|
Achievement of vIGA-AD Score of 'Clear' or 'Almost Clear' at Week 1
|
14.2 percentage of participants
|
6.2 percentage of participants
|
Adverse Events
Roflumilast Cream 0.15%
Vehicle Cream
Serious adverse events
| Measure |
Roflumilast Cream 0.15%
n=452 participants at risk
Participants applied roflumilast cream 0.15% qd for 4 weeks.
|
Vehicle Cream
n=232 participants at risk
Participants applied vehicle cream qd for 4 weeks.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Nerve compression
|
0.22%
1/452 • Up to ~29 days
All randomized participants who received ≥1 dose of study intervention are included, according to actual treatment received. Note that 1 participant was randomized to vehicle but did not receive ≥1 dose of study treatment; one additional participant was randomized to vehicle but instead received active roflumilast.
|
0.00%
0/232 • Up to ~29 days
All randomized participants who received ≥1 dose of study intervention are included, according to actual treatment received. Note that 1 participant was randomized to vehicle but did not receive ≥1 dose of study treatment; one additional participant was randomized to vehicle but instead received active roflumilast.
|
|
Infections and infestations
Staphylococcal scalded skin syndrome
|
0.22%
1/452 • Up to ~29 days
All randomized participants who received ≥1 dose of study intervention are included, according to actual treatment received. Note that 1 participant was randomized to vehicle but did not receive ≥1 dose of study treatment; one additional participant was randomized to vehicle but instead received active roflumilast.
|
0.00%
0/232 • Up to ~29 days
All randomized participants who received ≥1 dose of study intervention are included, according to actual treatment received. Note that 1 participant was randomized to vehicle but did not receive ≥1 dose of study treatment; one additional participant was randomized to vehicle but instead received active roflumilast.
|
|
General disorders
General physical health deterioration
|
0.22%
1/452 • Up to ~29 days
All randomized participants who received ≥1 dose of study intervention are included, according to actual treatment received. Note that 1 participant was randomized to vehicle but did not receive ≥1 dose of study treatment; one additional participant was randomized to vehicle but instead received active roflumilast.
|
0.00%
0/232 • Up to ~29 days
All randomized participants who received ≥1 dose of study intervention are included, according to actual treatment received. Note that 1 participant was randomized to vehicle but did not receive ≥1 dose of study treatment; one additional participant was randomized to vehicle but instead received active roflumilast.
|
|
Skin and subcutaneous tissue disorders
Dermatitis atopic
|
0.22%
1/452 • Up to ~29 days
All randomized participants who received ≥1 dose of study intervention are included, according to actual treatment received. Note that 1 participant was randomized to vehicle but did not receive ≥1 dose of study treatment; one additional participant was randomized to vehicle but instead received active roflumilast.
|
0.00%
0/232 • Up to ~29 days
All randomized participants who received ≥1 dose of study intervention are included, according to actual treatment received. Note that 1 participant was randomized to vehicle but did not receive ≥1 dose of study treatment; one additional participant was randomized to vehicle but instead received active roflumilast.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The process of coordinating publication efforts is detailed in the Clinical Trial Agreement.
- Publication restrictions are in place
Restriction type: OTHER