Trial Outcomes & Findings for Effect of Dupilumab (Anti-IL4Rα) on the Host-Microbe Interface in Atopic Dermatitis (NCT NCT03389893)
NCT ID: NCT03389893
Last Updated: 2021-10-04
Results Overview
Staphylococcus aureus (S. aureus) abundance was measured by microbial DNA (femA qPCR) on lesional skin at Day 28, measurement is expressed in relative Colony Forming Units (rCFU)/cm\^2). The abundance of S. aureus is summarized as the geometric mean ratio (and corresponding 95% confidence interval) between the dupilumab and placebo arms. The geometric mean ratio is reported from an ANCOVA model with fixed effects for clinical site, disease severity at Day 0 (as measured by EASI \>21.1 \[severe\] or ≤21.1 \[non-severe\]) and S. aureus abundance at Day 0.
TERMINATED
PHASE4
72 participants
Day 28 (Post treatment initiation)
2021-10-04
Participant Flow
72 participants were randomized from July 2018 to March 2020 from 9 clinical sites.First participant enrollment occurred on July 25, 2018.
Informed consent was obtained from potentially eligible individuals who underwent a screening visit to determine eligibility.
Participant milestones
| Measure |
Dupilumab
Participants received a loading dose of two 300 mg subcutaneous injections on Day 0 followed by 300 mg subcutaneous injections every two weeks (Days 14 and 28).
|
Placebo
Placebo contained the identical formulation as the dupilumab formulation without the active monoclonal antibody and was given by exactly the same route and schedule through Day 28.
|
Dupilumab to Open-Label Extension Dupilumab
Open Label Extension (OLE): Participants started a 10 week OLE on Day 42, beginning with a loading dose of two subcutaneously administered injections (one 300 mg dose of dupilumab and one dose of placebo, in order to protect prior masking/blind). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
Placebo to Open-Label Extension Dupilumab
Open Label Extension (OLE): Participants started a 10 week OLE on Day 42, beginning with a loading dose of dupilumab (two 300 mg subcutaneous injections \[total of 600 mg\]-protection of prior masking/blind maintained). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
|---|---|---|---|---|
|
Randomized Double Blind Period
STARTED
|
46
|
26
|
0
|
0
|
|
Randomized Double Blind Period
COMPLETED
|
45
|
26
|
0
|
0
|
|
Randomized Double Blind Period
NOT COMPLETED
|
1
|
0
|
0
|
0
|
|
Open Label Extension and Follow-Up
STARTED
|
0
|
0
|
45
|
26
|
|
Open Label Extension and Follow-Up
COMPLETED
|
0
|
0
|
41
|
25
|
|
Open Label Extension and Follow-Up
NOT COMPLETED
|
0
|
0
|
4
|
1
|
Reasons for withdrawal
| Measure |
Dupilumab
Participants received a loading dose of two 300 mg subcutaneous injections on Day 0 followed by 300 mg subcutaneous injections every two weeks (Days 14 and 28).
|
Placebo
Placebo contained the identical formulation as the dupilumab formulation without the active monoclonal antibody and was given by exactly the same route and schedule through Day 28.
|
Dupilumab to Open-Label Extension Dupilumab
Open Label Extension (OLE): Participants started a 10 week OLE on Day 42, beginning with a loading dose of two subcutaneously administered injections (one 300 mg dose of dupilumab and one dose of placebo, in order to protect prior masking/blind). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
Placebo to Open-Label Extension Dupilumab
Open Label Extension (OLE): Participants started a 10 week OLE on Day 42, beginning with a loading dose of dupilumab (two 300 mg subcutaneous injections \[total of 600 mg\]-protection of prior masking/blind maintained). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
|---|---|---|---|---|
|
Randomized Double Blind Period
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
|
Open Label Extension and Follow-Up
Lost to Follow-up
|
0
|
0
|
2
|
1
|
|
Open Label Extension and Follow-Up
Physician Decision
|
0
|
0
|
1
|
0
|
|
Open Label Extension and Follow-Up
Participant Moved
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Effect of Dupilumab (Anti-IL4Rα) on the Host-Microbe Interface in Atopic Dermatitis
Baseline characteristics by cohort
| Measure |
Dupilumab+Open Label Extension and Follow-Up
n=45 Participants
Participants received a loading dose of two 300 mg subcutaneous injections on Day 0 followed by 300 mg subcutaneous injections every two weeks (Days 14 and 28). Participants started a 10 week OLE on Day 42, beginning with a loading dose of two subcutaneously administered injections (one 300 mg dose of dupilumab and one dose of placebo, in order to protect prior masking/blind). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
Placebo+Open Label Extension and Follow-Up
n=26 Participants
Placebo contained the identical formulation as the dupilumab formulation without the active monoclonal antibody and was given by exactly the same route and schedule through Day 28. Participants started a 10 week OLE on Day 42, beginning with a loading dose of dupilumab (two 300 mg subcutaneous injections \[total of 600 mg\]-protection of prior masking/blind maintained). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
Total
n=71 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
36.6 years
STANDARD_DEVIATION 15.56 • n=5 Participants
|
37.3 years
STANDARD_DEVIATION 15.61 • n=7 Participants
|
36.8 years
STANDARD_DEVIATION 15.47 • n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
47 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
39 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
21 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
45 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
71 Participants
n=5 Participants
|
|
Body Weight
|
80.7 kilograms (Kg)
STANDARD_DEVIATION 19.45 • n=5 Participants
|
79.4 kilograms (Kg)
STANDARD_DEVIATION 18.58 • n=7 Participants
|
80.2 kilograms (Kg)
STANDARD_DEVIATION 19.01 • n=5 Participants
|
|
Height
|
170.9 centimeters (Cm)
STANDARD_DEVIATION 9.27 • n=5 Participants
|
175.3 centimeters (Cm)
STANDARD_DEVIATION 11.74 • n=7 Participants
|
172.5 centimeters (Cm)
STANDARD_DEVIATION 10.38 • n=5 Participants
|
|
Body Mass Index (BMI)
|
27.5 Kg/m^2
STANDARD_DEVIATION 5.69 • n=5 Participants
|
25.7 Kg/m^2
STANDARD_DEVIATION 4.90 • n=7 Participants
|
26.9 Kg/m^2
STANDARD_DEVIATION 5.45 • n=5 Participants
|
|
SCORing Atopic Dermatitis (SCORAD)
|
62.1 units on a scale
STANDARD_DEVIATION 11.7 • n=5 Participants
|
59.9 units on a scale
STANDARD_DEVIATION 10.86 • n=7 Participants
|
61.3 units on a scale
STANDARD_DEVIATION 11.38 • n=5 Participants
|
|
Eczema Area and Severity Index (EASI) Score
|
28.4 units on a scale
STANDARD_DEVIATION 12.16 • n=5 Participants
|
28.6 units on a scale
STANDARD_DEVIATION 10.89 • n=7 Participants
|
28.5 units on a scale
STANDARD_DEVIATION 11.63 • n=5 Participants
|
|
Eczema Area and Severity Index (EASI) Score < 21.1
|
16 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Nottingham Eczema Severity Score
|
13.5 units on a scale
STANDARD_DEVIATION 1.49 • n=5 Participants
|
13.6 units on a scale
STANDARD_DEVIATION 1.21 • n=7 Participants
|
13.5 units on a scale
STANDARD_DEVIATION 1.38 • n=5 Participants
|
|
Investigator Global Assessment (IGA)
Moderate
|
16 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Investigator Global Assessment (IGA)
Severe
|
29 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Average itch in the past 24 hours as assessed by Pruritus Numerical Rating Scale (NRS)
|
6.7 units on a scale
STANDARD_DEVIATION 2.17 • n=5 Participants
|
7.0 units on a scale
STANDARD_DEVIATION 1.48 • n=7 Participants
|
6.8 units on a scale
STANDARD_DEVIATION 1.94 • n=5 Participants
|
|
Self-reported history of Eczema Herpeticum
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Self-reported history of Staph infection
|
15 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Self-reported history of food allergy
|
15 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Self-reported history of animal allergies
|
30 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
49 Participants
n=5 Participants
|
|
Self-reported pets living in the participant's home
|
26 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
|
Self-reported smoking in the participant's home
|
11 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 28 (Post treatment initiation)Population: Modified intent-to-treat: All participants who were randomized and have Staphylococcus aureus abundance measured at Day 0 and Day 28.
Staphylococcus aureus (S. aureus) abundance was measured by microbial DNA (femA qPCR) on lesional skin at Day 28, measurement is expressed in relative Colony Forming Units (rCFU)/cm\^2). The abundance of S. aureus is summarized as the geometric mean ratio (and corresponding 95% confidence interval) between the dupilumab and placebo arms. The geometric mean ratio is reported from an ANCOVA model with fixed effects for clinical site, disease severity at Day 0 (as measured by EASI \>21.1 \[severe\] or ≤21.1 \[non-severe\]) and S. aureus abundance at Day 0.
Outcome measures
| Measure |
Dupilumab+Open Label Extension and Follow-Up
n=45 Participants
Participants received a loading dose of two 300 mg subcutaneous injections on Day 0 followed by 300 mg subcutaneous injections every two weeks (Days 14 and 28). Participants started a 10 week OLE on Day 42, beginning with a loading dose of two subcutaneously administered injections (one 300 mg dose of dupilumab and one dose of placebo, in order to protect prior masking/blind). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
Placebo+Open Label Extension and Follow-Up
n=26 Participants
Placebo contained the identical formulation as the dupilumab formulation without the active monoclonal antibody and was given by exactly the same route and schedule through Day 28. Participants started a 10 week OLE on Day 42, beginning with a loading dose of dupilumab (two 300 mg subcutaneous injections \[total of 600 mg\]-protection of prior masking/blind maintained). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
|---|---|---|
|
Staphylococcus Aureus Abundance on Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
|
86.01 Relative Colony Forming Unit (rCFU)/cm^2
Interval 34.07 to 217.11
|
2608.4 Relative Colony Forming Unit (rCFU)/cm^2
Interval 835.02 to 8147.99
|
SECONDARY outcome
Timeframe: Day 0 (Prior to treatment), 3, 7, 14, 21, 42, 77 and 112Population: Modified intent-to-treat: All participants who were randomized and have Staphylococcus aureus abundance measured at Day 0 and Day 28.
Staphylococcus aureus (S. aureus) abundance was measured by microbial DNA (femA qPCR) on lesional skin at Days 0, 3, 7, 14, 21, 42, 77 and 112. The abundance of S. aureus is summarized as the geometric mean ratio (GMR) and corresponding 95% confidence interval between the dupilumab and placebo arms. The GMR is reported from a linear mixed model for repeated measures with fixed effects for S. aureus abundance on lesional skin at Day 0, treatment arm, clinical site, disease severity at Day 0 as measured by EASI ≥ 21.1 or \< 21.1, time point of measurement (as a categorical variable), and an interaction term between treatment arm and pre-specified time point(s). A linear mixed model similar to the model specified above was fit for every time point measured. The model was used to estimate the GMR between treatment arms at Days 77 and 112 and the ratio within treatment arm between Day 77 and Day 42 and between Day 112 and Day 42.
Outcome measures
| Measure |
Dupilumab+Open Label Extension and Follow-Up
n=45 Participants
Participants received a loading dose of two 300 mg subcutaneous injections on Day 0 followed by 300 mg subcutaneous injections every two weeks (Days 14 and 28). Participants started a 10 week OLE on Day 42, beginning with a loading dose of two subcutaneously administered injections (one 300 mg dose of dupilumab and one dose of placebo, in order to protect prior masking/blind). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
Placebo+Open Label Extension and Follow-Up
n=26 Participants
Placebo contained the identical formulation as the dupilumab formulation without the active monoclonal antibody and was given by exactly the same route and schedule through Day 28. Participants started a 10 week OLE on Day 42, beginning with a loading dose of dupilumab (two 300 mg subcutaneous injections \[total of 600 mg\]-protection of prior masking/blind maintained). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
|---|---|---|
|
Staphylococcus Aureus Abundance on Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 3
|
833.82 Relative Colony Forming Unit (rCFU)/cm^2
Interval 411.45 to 1689.74
|
3028.88 Relative Colony Forming Unit (rCFU)/cm^2
Interval 1256.63 to 7300.56
|
|
Staphylococcus Aureus Abundance on Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 7
|
337.48 Relative Colony Forming Unit (rCFU)/cm^2
Interval 138.69 to 821.16
|
900.59 Relative Colony Forming Unit (rCFU)/cm^2
Interval 290.95 to 2787.59
|
|
Staphylococcus Aureus Abundance on Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 14
|
205.06 Relative Colony Forming Unit (rCFU)/cm^2
Interval 91.16 to 461.27
|
2690.79 Relative Colony Forming Unit (rCFU)/cm^2
Interval 964.61 to 7505.96
|
|
Staphylococcus Aureus Abundance on Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 21
|
179.91 Relative Colony Forming Unit (rCFU)/cm^2
Interval 80.71 to 401.02
|
2468.64 Relative Colony Forming Unit (rCFU)/cm^2
Interval 916.89 to 6646.62
|
|
Staphylococcus Aureus Abundance on Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 42
|
177.79 Relative Colony Forming Unit (rCFU)/cm^2
Interval 79.02 to 400.05
|
1112.55 Relative Colony Forming Unit (rCFU)/cm^2
Interval 409.02 to 3026.14
|
|
Staphylococcus Aureus Abundance on Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 77
|
56.85 Relative Colony Forming Unit (rCFU)/cm^2
Interval 20.44 to 158.08
|
150.81 Relative Colony Forming Unit (rCFU)/cm^2
Interval 43.93 to 517.81
|
|
Staphylococcus Aureus Abundance on Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 112
|
42.35 Relative Colony Forming Unit (rCFU)/cm^2
Interval 14.91 to 120.28
|
174.19 Relative Colony Forming Unit (rCFU)/cm^2
Interval 53.18 to 570.53
|
SECONDARY outcome
Timeframe: Day 0 (Prior to treatment), 3, 7, 14, 21, 28, 42, 77 and 112Population: Modified intent-to-treat: All participants who were randomized and have Staphylococcus aureus abundance measured at Day 0 and Day 28.
Staphylococcus aureus (S. aureus) abundance was measured by microbial DNA (femA qPCR) on non-lesional skin at Days 0, 3, 7, 14, 21, 28, 42, 77 and 112. The abundance of S. aureus is summarized as the geometric mean ratio (GMR) and corresponding 95% confidence interval between the dupilumab and placebo arms. The GMR is reported from a linear mixed model for repeated measures with fixed effects for S. aureus abundance on non-lesional skin at Day 0, treatment arm, clinical site, disease severity at Day 0 as measured by EASI ≥ 21.1 or \< 21.1, time point of measurement (as a categorical variable), and an interaction term between treatment arm and pre-specified time point(s). A linear mixed model similar to the model specified above was fit for every time point measured. The model estimated the GMR between treatment arms at Days 77 and 112 and the ratio within treatment arm between Day 77 and Day 42 and between Day 112 and Day 42.
Outcome measures
| Measure |
Dupilumab+Open Label Extension and Follow-Up
n=45 Participants
Participants received a loading dose of two 300 mg subcutaneous injections on Day 0 followed by 300 mg subcutaneous injections every two weeks (Days 14 and 28). Participants started a 10 week OLE on Day 42, beginning with a loading dose of two subcutaneously administered injections (one 300 mg dose of dupilumab and one dose of placebo, in order to protect prior masking/blind). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
Placebo+Open Label Extension and Follow-Up
n=26 Participants
Placebo contained the identical formulation as the dupilumab formulation without the active monoclonal antibody and was given by exactly the same route and schedule through Day 28. Participants started a 10 week OLE on Day 42, beginning with a loading dose of dupilumab (two 300 mg subcutaneous injections \[total of 600 mg\]-protection of prior masking/blind maintained). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
|---|---|---|
|
Staphylococcus Aureus Abundance on Non-lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 3
|
221.75 Relative Colony Forming Unit (rCFU)/cm^2
Interval 99.74 to 493.01
|
277.21 Relative Colony Forming Unit (rCFU)/cm^2
Interval 100.25 to 766.52
|
|
Staphylococcus Aureus Abundance on Non-lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 7
|
143.19 Relative Colony Forming Unit (rCFU)/cm^2
Interval 66.56 to 308.04
|
539.97 Relative Colony Forming Unit (rCFU)/cm^2
Interval 201.61 to 1446.22
|
|
Staphylococcus Aureus Abundance on Non-lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 14
|
118.15 Relative Colony Forming Unit (rCFU)/cm^2
Interval 57.86 to 241.27
|
326.55 Relative Colony Forming Unit (rCFU)/cm^2
Interval 132.38 to 805.48
|
|
Staphylococcus Aureus Abundance on Non-lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 42
|
98.97 Relative Colony Forming Unit (rCFU)/cm^2
Interval 44.01 to 222.55
|
191.30 Relative Colony Forming Unit (rCFU)/cm^2
Interval 70.36 to 520.1
|
|
Staphylococcus Aureus Abundance on Non-lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 112
|
76.71 Relative Colony Forming Unit (rCFU)/cm^2
Interval 27.37 to 214.99
|
146.35 Relative Colony Forming Unit (rCFU)/cm^2
Interval 45.23 to 473.54
|
|
Staphylococcus Aureus Abundance on Non-lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 21
|
93.32 Relative Colony Forming Unit (rCFU)/cm^2
Interval 44.33 to 196.46
|
128.56 Relative Colony Forming Unit (rCFU)/cm^2
Interval 51.17 to 323.01
|
|
Staphylococcus Aureus Abundance on Non-lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 28
|
61.67 Relative Colony Forming Unit (rCFU)/cm^2
Interval 29.55 to 128.72
|
369.74 Relative Colony Forming Unit (rCFU)/cm^2
Interval 145.96 to 936.6
|
|
Staphylococcus Aureus Abundance on Non-lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 77
|
86.91 Relative Colony Forming Unit (rCFU)/cm^2
Interval 32.27 to 234.09
|
182.19 Relative Colony Forming Unit (rCFU)/cm^2
Interval 57.37 to 578.6
|
SECONDARY outcome
Timeframe: Day 0 (Prior to treatment), 3, 7, 14, 21, 28, 42, 77 and 112Population: Modified intent-to-treat (all participants who were randomized and have Staphylococcus aureus abundance measured at Day 0 and Day 28) with evaluable basal TEWL at any post-baseline time point.
TEWL assessment is a noninvasive in vivo measurement of water loss across the stratum corneum that is used to characterize skin barrier function. Basal TEWL =baseline measure (prior to tape stripping). An increase in TEWL values shows damage to the skin barrier function. Basal TEWL was measured on non-lesional and lesional skin. Basal TEWL is summarized as the mean difference between the dupilumab and placebo arms. The mean difference is reported from two linear mixed models for repeated measures (lesional and non-lesional) with fixed effects for treatment arm, basal TEWL at Day 0, clinical site, and disease severity at Day 0 as measured by EASI ≥ 21.1 or \< 21.1 at Days 3, 7, 14, 21, 28, and 42. Two linear mixed models similar to the models specified above were fit for every time point measured. The model was used to estimate the mean difference between treatment arms at Days 77 and 112 and the ratio within treatment arm between Day 77 and Day 42 and between Day 112 and Day 42.
Outcome measures
| Measure |
Dupilumab+Open Label Extension and Follow-Up
n=44 Participants
Participants received a loading dose of two 300 mg subcutaneous injections on Day 0 followed by 300 mg subcutaneous injections every two weeks (Days 14 and 28). Participants started a 10 week OLE on Day 42, beginning with a loading dose of two subcutaneously administered injections (one 300 mg dose of dupilumab and one dose of placebo, in order to protect prior masking/blind). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
Placebo+Open Label Extension and Follow-Up
n=26 Participants
Placebo contained the identical formulation as the dupilumab formulation without the active monoclonal antibody and was given by exactly the same route and schedule through Day 28. Participants started a 10 week OLE on Day 42, beginning with a loading dose of dupilumab (two 300 mg subcutaneous injections \[total of 600 mg\]-protection of prior masking/blind maintained). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
|---|---|---|
|
Transepidermal Water Loss (TEWL) of Non-lesional and Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 7 - Lesional
|
40.08 g/m^2/hour
Interval 33.79 to 46.37
|
41.15 g/m^2/hour
Interval 32.7 to 49.61
|
|
Transepidermal Water Loss (TEWL) of Non-lesional and Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 28 - Lesional
|
24.93 g/m^2/hour
Interval 19.97 to 29.89
|
32.03 g/m^2/hour
Interval 25.93 to 38.13
|
|
Transepidermal Water Loss (TEWL) of Non-lesional and Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 42 - Lesional
|
25.34 g/m^2/hour
Interval 20.58 to 30.1
|
33.33 g/m^2/hour
Interval 27.46 to 39.19
|
|
Transepidermal Water Loss (TEWL) of Non-lesional and Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 3 - Non-lesional
|
24.24 g/m^2/hour
Interval 20.87 to 27.6
|
23.55 g/m^2/hour
Interval 19.05 to 28.05
|
|
Transepidermal Water Loss (TEWL) of Non-lesional and Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 7 - Non-lesional
|
22.58 g/m^2/hour
Interval 19.6 to 25.57
|
20.23 g/m^2/hour
Interval 16.28 to 24.18
|
|
Transepidermal Water Loss (TEWL) of Non-lesional and Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 14 - Non-lesional
|
23.30 g/m^2/hour
Interval 19.9 to 26.71
|
23.20 g/m^2/hour
Interval 18.77 to 27.63
|
|
Transepidermal Water Loss (TEWL) of Non-lesional and Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 21 - Non-lesional
|
19.55 g/m^2/hour
Interval 16.54 to 22.57
|
22.86 g/m^2/hour
Interval 18.78 to 26.95
|
|
Transepidermal Water Loss (TEWL) of Non-lesional and Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 28 - Non-lesional
|
17.55 g/m^2/hour
Interval 15.08 to 20.03
|
19.31 g/m^2/hour
Interval 16.11 to 22.51
|
|
Transepidermal Water Loss (TEWL) of Non-lesional and Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 42 - Non-lesional
|
16.95 g/m^2/hour
Interval 14.5 to 19.4
|
19.12 g/m^2/hour
Interval 16.17 to 22.07
|
|
Transepidermal Water Loss (TEWL) of Non-lesional and Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 77 - Non-lesional
|
15.45 g/m^2/hour
Interval 12.6 to 18.29
|
17.55 g/m^2/hour
Interval 14.27 to 20.82
|
|
Transepidermal Water Loss (TEWL) of Non-lesional and Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 112 - Non-lesional
|
13.97 g/m^2/hour
Interval 11.55 to 16.39
|
15.86 g/m^2/hour
Interval 13.05 to 18.68
|
|
Transepidermal Water Loss (TEWL) of Non-lesional and Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 3 - Lesional
|
33.46 g/m^2/hour
Interval 28.52 to 38.39
|
42.99 g/m^2/hour
Interval 36.57 to 49.41
|
|
Transepidermal Water Loss (TEWL) of Non-lesional and Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 14 - Lesional
|
31.96 g/m^2/hour
Interval 27.19 to 36.74
|
31.49 g/m^2/hour
Interval 25.47 to 37.51
|
|
Transepidermal Water Loss (TEWL) of Non-lesional and Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 21 - Lesional
|
28.14 g/m^2/hour
Interval 23.25 to 33.02
|
34.11 g/m^2/hour
Interval 27.74 to 40.48
|
|
Transepidermal Water Loss (TEWL) of Non-lesional and Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 77 - Lesional
|
24.54 g/m^2/hour
Interval 18.94 to 30.13
|
25.58 g/m^2/hour
Interval 19.14 to 32.02
|
|
Transepidermal Water Loss (TEWL) of Non-lesional and Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 112 - Lesional
|
22.99 g/m^2/hour
Interval 16.79 to 29.18
|
22.82 g/m^2/hour
Interval 15.87 to 29.78
|
SECONDARY outcome
Timeframe: Day 0 (Prior to treatment), 7, 14, 21, 28, 42, 77 and 112Population: Modified intent-to-treat (all participants who were randomized and have Staphylococcus aureus abundance measured at Day 0 and Day 28) with evaluable TEWL AUC at any post-baseline time point.
TEWL skin barrier assessment was assessed prior to tape stripping and repeated after 5, 10, and 15 tape strips. TEWL AUC was calculated using the trapezoidal rule and represents skin barrier integrity. An increase in TEWL values shows damage to the skin barrier function. TEWL AUC was measured on non-lesional skin at Days 0, 7, 14, 21, 28, 42, 77 and 112. The mean difference (between Groups) is reported from a linear mixed model for repeated measures with a random effect for participant and fixed effects for treatment arm, TEWL AUC at Day 0, clinical site, and disease severity at Day 0 as measured by EASI ≥ 21.1 or \< 21.1 at Days 7, 14, 21, 28, and 42. A linear mixed model similar to the model specified above was fit for every time point measured. The model was used to estimate the mean difference between treatment arms at Days 77 and 112 and the mean difference within treatment arm between Day 77 and Day 42 and between Day 112 and Day 42.
Outcome measures
| Measure |
Dupilumab+Open Label Extension and Follow-Up
n=43 Participants
Participants received a loading dose of two 300 mg subcutaneous injections on Day 0 followed by 300 mg subcutaneous injections every two weeks (Days 14 and 28). Participants started a 10 week OLE on Day 42, beginning with a loading dose of two subcutaneously administered injections (one 300 mg dose of dupilumab and one dose of placebo, in order to protect prior masking/blind). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
Placebo+Open Label Extension and Follow-Up
n=26 Participants
Placebo contained the identical formulation as the dupilumab formulation without the active monoclonal antibody and was given by exactly the same route and schedule through Day 28. Participants started a 10 week OLE on Day 42, beginning with a loading dose of dupilumab (two 300 mg subcutaneous injections \[total of 600 mg\]-protection of prior masking/blind maintained). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
|---|---|---|
|
Transepidermal Water Loss (TEWL) Area Under the Curve (AUC) on Non-Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 7
|
527.79 g/m^2/hour
Interval 466.25 to 589.33
|
442.74 g/m^2/hour
Interval 363.86 to 521.62
|
|
Transepidermal Water Loss (TEWL) Area Under the Curve (AUC) on Non-Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 14
|
504.80 g/m^2/hour
Interval 426.5 to 583.09
|
526.70 g/m^2/hour
Interval 424.66 to 628.74
|
|
Transepidermal Water Loss (TEWL) Area Under the Curve (AUC) on Non-Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 28
|
390.92 g/m^2/hour
Interval 328.07 to 453.76
|
483.02 g/m^2/hour
Interval 405.23 to 560.81
|
|
Transepidermal Water Loss (TEWL) Area Under the Curve (AUC) on Non-Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 21
|
451.40 g/m^2/hour
Interval 385.72 to 517.07
|
533.89 g/m^2/hour
Interval 444.83 to 622.96
|
|
Transepidermal Water Loss (TEWL) Area Under the Curve (AUC) on Non-Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 42
|
397.22 g/m^2/hour
Interval 341.24 to 453.2
|
445.98 g/m^2/hour
Interval 378.96 to 513.01
|
|
Transepidermal Water Loss (TEWL) Area Under the Curve (AUC) on Non-Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 77
|
363.15 g/m^2/hour
Interval 298.76 to 427.53
|
417.52 g/m^2/hour
Interval 344.23 to 490.81
|
|
Transepidermal Water Loss (TEWL) Area Under the Curve (AUC) on Non-Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 112
|
320.95 g/m^2/hour
Interval 266.16 to 375.74
|
343.92 g/m^2/hour
Interval 284.63 to 403.2
|
SECONDARY outcome
Timeframe: Day 0 (Prior to treatment), 7, 14, 21, 28, 42, 77 and 112Population: Modified intent-to-treat (all participants who were randomized and have Staphylococcus aureus abundance measured at Day 0 and Day 28) with evaluable TEWL at any post-baseline time point.
The skin tape strip collection was comprised of 1 set of 15 strips from non-lesional skin and was collected as part of the TEWL skin barrier assessment. The TEWL values measured at every 5 tape strips were used to model the TEWL slope. TEWL slope assesses skin barrier integrity. An increase in TEWL values shows damage to the skin barrier function. TEWL slope is summarized as the mean difference (and corresponding 95% confidence interval) between the dupilumab and placebo arms. The mean difference in slope for each Day is reported from a linear mixed model for repeated measures with a fixed effects for basal TEWL prior to tape stripping, treatment arm, clinical site, disease severity at Day 0 as measured by EASI ≥ 21.1 or \< 21.1, tape strip number, and an interaction term between treatment arm and tape strip number.
Outcome measures
| Measure |
Dupilumab+Open Label Extension and Follow-Up
n=43 Participants
Participants received a loading dose of two 300 mg subcutaneous injections on Day 0 followed by 300 mg subcutaneous injections every two weeks (Days 14 and 28). Participants started a 10 week OLE on Day 42, beginning with a loading dose of two subcutaneously administered injections (one 300 mg dose of dupilumab and one dose of placebo, in order to protect prior masking/blind). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
Placebo+Open Label Extension and Follow-Up
n=26 Participants
Placebo contained the identical formulation as the dupilumab formulation without the active monoclonal antibody and was given by exactly the same route and schedule through Day 28. Participants started a 10 week OLE on Day 42, beginning with a loading dose of dupilumab (two 300 mg subcutaneous injections \[total of 600 mg\]-protection of prior masking/blind maintained). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
|---|---|---|
|
Transepidermal Water Loss (TEWL) Slope on Non-Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 21
|
1.43 g/m^2/hour
Interval 0.95 to 1.91
|
1.98 g/m^2/hour
Interval 1.37 to 2.6
|
|
Transepidermal Water Loss (TEWL) Slope on Non-Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 7
|
1.77 g/m^2/hour
Interval 1.25 to 2.29
|
1.84 g/m^2/hour
Interval 1.18 to 2.51
|
|
Transepidermal Water Loss (TEWL) Slope on Non-Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 14
|
1.56 g/m^2/hour
Interval 1.17 to 1.96
|
1.78 g/m^2/hour
Interval 1.28 to 2.28
|
|
Transepidermal Water Loss (TEWL) Slope on Non-Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 28
|
1.38 g/m^2/hour
Interval 0.97 to 1.79
|
1.73 g/m^2/hour
Interval 1.23 to 2.23
|
|
Transepidermal Water Loss (TEWL) Slope on Non-Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 42
|
1.47 g/m^2/hour
Interval 0.96 to 1.97
|
1.76 g/m^2/hour
Interval 1.15 to 2.37
|
|
Transepidermal Water Loss (TEWL) Slope on Non-Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 77
|
1.15 g/m^2/hour
Interval 0.79 to 1.52
|
1.42 g/m^2/hour
Interval 0.99 to 1.85
|
|
Transepidermal Water Loss (TEWL) Slope on Non-Lesional Skin, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 112
|
1.03 g/m^2/hour
Interval 0.7 to 1.36
|
1.30 g/m^2/hour
Interval 0.94 to 1.67
|
SECONDARY outcome
Timeframe: Day 0 (Prior to treatment), 3, 7, 14, 21, 28, 42, 77 and 112Population: Modified intent-to-treat: All participants who were randomized and have Staphylococcus aureus abundance measured at Day 0 and Day 28.
EASI is a composite score (range: 0-72) measuring physical signs of atopic dermatitis, including area of involvement and severity. Severity components include: erythema, papulation, excoriation and lichenification \[0=absent, 1=mild, 2=moderate, 3=severe\] for each body region (head/neck, trunk, arms, legs). Area of involvement (%) is assessed for each body region. Area and severity of each body region is weighted based on size of region, and region scores are added for the total score. Scores ≤7 are considered mild, \>7 and ≤21 are considered moderate, and \>21 are considered severe. The mean EASI score in each treatment arm is reported from a linear mixed model for repeated measures with fixed effects for EASI at Day 0, treatment arm, clinical site, time point of measurement, and an interaction term between treatment arm and pre-specified time point(s), Additionally, a similar model was fit using all time points.
Outcome measures
| Measure |
Dupilumab+Open Label Extension and Follow-Up
n=45 Participants
Participants received a loading dose of two 300 mg subcutaneous injections on Day 0 followed by 300 mg subcutaneous injections every two weeks (Days 14 and 28). Participants started a 10 week OLE on Day 42, beginning with a loading dose of two subcutaneously administered injections (one 300 mg dose of dupilumab and one dose of placebo, in order to protect prior masking/blind). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
Placebo+Open Label Extension and Follow-Up
n=26 Participants
Placebo contained the identical formulation as the dupilumab formulation without the active monoclonal antibody and was given by exactly the same route and schedule through Day 28. Participants started a 10 week OLE on Day 42, beginning with a loading dose of dupilumab (two 300 mg subcutaneous injections \[total of 600 mg\]-protection of prior masking/blind maintained). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
|---|---|---|
|
Eczema Area and Severity Index (EASI) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 7
|
25.96 units on a scale
Interval 23.56 to 28.36
|
24.92 units on a scale
Interval 21.92 to 27.91
|
|
Eczema Area and Severity Index (EASI) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 3
|
26.52 units on a scale
Interval 24.21 to 28.83
|
24.60 units on a scale
Interval 21.73 to 27.46
|
|
Eczema Area and Severity Index (EASI) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 14
|
20.36 units on a scale
Interval 17.92 to 22.81
|
23.13 units on a scale
Interval 20.08 to 26.19
|
|
Eczema Area and Severity Index (EASI) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 21
|
16.57 units on a scale
Interval 13.98 to 19.16
|
22.75 units on a scale
Interval 19.51 to 25.98
|
|
Eczema Area and Severity Index (EASI) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 28
|
15.09 units on a scale
Interval 12.47 to 17.72
|
21.67 units on a scale
Interval 18.36 to 24.99
|
|
Eczema Area and Severity Index (EASI) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 42
|
11.90 units on a scale
Interval 9.1 to 14.7
|
20.40 units on a scale
Interval 16.83 to 23.96
|
|
Eczema Area and Severity Index (EASI) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 77
|
8.84 units on a scale
Interval 6.67 to 11.0
|
7.54 units on a scale
Interval 4.89 to 10.19
|
|
Eczema Area and Severity Index (EASI) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 112
|
6.97 units on a scale
Interval 5.19 to 8.76
|
5.53 units on a scale
Interval 3.45 to 7.61
|
SECONDARY outcome
Timeframe: Day 0 (Prior to treatment), 3, 7, 14, 21, 28, 42, 77 and 112Population: Modified intent-to-treat: All participants who were randomized and have Staphylococcus aureus abundance measured at Day 0 and Day 28.
Investigator Global Assessment (IGA) score is a subjective scale measuring disease severity. Based on a 5-point scale from 0 (completely clear) to 4 (severe). Defined score of 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe. The mean IGA score in each treatment arm is reported from a linear mixed model for repeated measures with fixed effects for IGA at Day 0, treatment arm, clinical site, disease severity at Day 0 as measured by EASI ≥ 21.1 or \< 21.1, time point of measurement, and an interaction term between treatment arm and pre-specified time point(s). Additionally, a similar model was fit using all time points.
Outcome measures
| Measure |
Dupilumab+Open Label Extension and Follow-Up
n=45 Participants
Participants received a loading dose of two 300 mg subcutaneous injections on Day 0 followed by 300 mg subcutaneous injections every two weeks (Days 14 and 28). Participants started a 10 week OLE on Day 42, beginning with a loading dose of two subcutaneously administered injections (one 300 mg dose of dupilumab and one dose of placebo, in order to protect prior masking/blind). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
Placebo+Open Label Extension and Follow-Up
n=26 Participants
Placebo contained the identical formulation as the dupilumab formulation without the active monoclonal antibody and was given by exactly the same route and schedule through Day 28. Participants started a 10 week OLE on Day 42, beginning with a loading dose of dupilumab (two 300 mg subcutaneous injections \[total of 600 mg\]-protection of prior masking/blind maintained). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
|---|---|---|
|
Investigator Global Assessment (IGA) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 7
|
3.32 units on a scale
Interval 3.18 to 3.45
|
3.28 units on a scale
Interval 3.11 to 3.45
|
|
Investigator Global Assessment (IGA) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 28
|
2.72 units on a scale
Interval 2.52 to 2.92
|
3.28 units on a scale
Interval 3.02 to 3.54
|
|
Investigator Global Assessment (IGA) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 3
|
3.49 units on a scale
Interval 3.34 to 3.64
|
3.28 units on a scale
Interval 3.09 to 3.47
|
|
Investigator Global Assessment (IGA) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 14
|
3.12 units on a scale
Interval 2.96 to 3.28
|
3.16 units on a scale
Interval 2.96 to 3.37
|
|
Investigator Global Assessment (IGA) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 21
|
2.86 units on a scale
Interval 2.67 to 3.05
|
3.20 units on a scale
Interval 2.96 to 3.44
|
|
Investigator Global Assessment (IGA) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 42
|
2.58 units on a scale
Interval 2.36 to 2.81
|
3.24 units on a scale
Interval 2.95 to 3.53
|
|
Investigator Global Assessment (IGA) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 77
|
2.20 units on a scale
Interval 1.92 to 2.48
|
2.20 units on a scale
Interval 1.84 to 2.55
|
|
Investigator Global Assessment (IGA) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 112
|
1.94 units on a scale
Interval 1.63 to 2.24
|
1.89 units on a scale
Interval 1.51 to 2.27
|
SECONDARY outcome
Timeframe: Day 0 (Prior to treatment), 3, 7, 14, 21, 28, 42, 77 and 112Population: Modified intent-to-treat: All participants who were randomized and have Staphylococcus aureus abundance measured at Day 0 and Day 28.
SCORAD is a composite index comprising a) the amount/extent of body surface area affected, b) subjective symptom visual analog assessments of itch and sleep loss \[itch: 0 (no itch) to 10 (worst itch imaginable) / sleep loss: 0 (no sleep loss) to 10 (worst imaginable sleep loss)\], and c) 6 disease intensity assessments \[dryness, erythema, edema/papulation, excoriation, lichenification and oozing/crusting, each graded from 0-3: 0 (none), 1 (mild), 2 (moderate) and 3 (severe). The score ranges from 0 (no AD present) to 103 (severe). The mean SCORAD score in each treatment arm is reported from a linear mixed model for repeated measures with fixed effects for SCORAD at Day 0, treatment arm, clinical site, disease severity at Day 0 as measured by EASI ≥ 21.1 or \< 21.1, time point of measurement, and an interaction term between treatment arm and pre-specified time point(s). Additionally, a similar model was fit using all time points.
Outcome measures
| Measure |
Dupilumab+Open Label Extension and Follow-Up
n=45 Participants
Participants received a loading dose of two 300 mg subcutaneous injections on Day 0 followed by 300 mg subcutaneous injections every two weeks (Days 14 and 28). Participants started a 10 week OLE on Day 42, beginning with a loading dose of two subcutaneously administered injections (one 300 mg dose of dupilumab and one dose of placebo, in order to protect prior masking/blind). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
Placebo+Open Label Extension and Follow-Up
n=26 Participants
Placebo contained the identical formulation as the dupilumab formulation without the active monoclonal antibody and was given by exactly the same route and schedule through Day 28. Participants started a 10 week OLE on Day 42, beginning with a loading dose of dupilumab (two 300 mg subcutaneous injections \[total of 600 mg\]-protection of prior masking/blind maintained). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
|---|---|---|
|
SCORing Atopic Dermatitis (SCORAD) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 7
|
54.78 units on a scale
Interval 51.7 to 57.86
|
54.96 units on a scale
Interval 51.14 to 58.78
|
|
SCORing Atopic Dermatitis (SCORAD) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 21
|
39.40 units on a scale
Interval 35.53 to 43.28
|
51.87 units on a scale
Interval 47.01 to 56.73
|
|
SCORing Atopic Dermatitis (SCORAD) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 3
|
56.91 units on a scale
Interval 53.46 to 60.35
|
53.12 units on a scale
Interval 48.78 to 57.46
|
|
SCORing Atopic Dermatitis (SCORAD) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 14
|
46.55 units on a scale
Interval 43.09 to 50.0
|
52.01 units on a scale
Interval 47.66 to 56.73
|
|
SCORing Atopic Dermatitis (SCORAD) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 28
|
36.34 units on a scale
Interval 32.64 to 40.04
|
50.99 units on a scale
Interval 46.33 to 55.66
|
|
SCORing Atopic Dermatitis (SCORAD) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 42
|
32.22 units on a scale
Interval 28.38 to 36.06
|
51.02 units on a scale
Interval 46.15 to 55.9
|
|
SCORing Atopic Dermatitis (SCORAD) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 77
|
27.63 units on a scale
Interval 23.87 to 31.38
|
28.18 units on a scale
Interval 23.53 to 32.83
|
|
SCORing Atopic Dermatitis (SCORAD) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 112
|
23.92 units on a scale
Interval 20.25 to 27.59
|
25.01 units on a scale
Interval 20.57 to 29.46
|
SECONDARY outcome
Timeframe: Day 0 (Prior to treatment), 3, 7, 14, 21, 28, 42, 77 and 112Population: Modified intent-to-treat: All participants who were randomized and have Staphylococcus aureus abundance measured at Day 0 and Day 28.
Pruritus NRS scale is an assessment tool that is used to report the average intensity of a participant's pruritus (itch) during a 24-hour recall period. Participants were asked to report the average itch experienced during the past 24 hours on a scale of 0 - 10 \[0= no itch; 10= worst imaginable itch\]). The mean Pruritus NRS score in each treatment arm is reported from a linear mixed model for repeated measures with fixed effects for Pruritus NRS at Day 0, treatment arm, clinical site, disease severity at Day 0 as measured by EASI ≥ 21.1 or \< 21.1, time point of measurement, and an interaction term between treatment arm and pre-specified time point(s). Additionally, a similar model was fit using all time points.
Outcome measures
| Measure |
Dupilumab+Open Label Extension and Follow-Up
n=45 Participants
Participants received a loading dose of two 300 mg subcutaneous injections on Day 0 followed by 300 mg subcutaneous injections every two weeks (Days 14 and 28). Participants started a 10 week OLE on Day 42, beginning with a loading dose of two subcutaneously administered injections (one 300 mg dose of dupilumab and one dose of placebo, in order to protect prior masking/blind). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
Placebo+Open Label Extension and Follow-Up
n=26 Participants
Placebo contained the identical formulation as the dupilumab formulation without the active monoclonal antibody and was given by exactly the same route and schedule through Day 28. Participants started a 10 week OLE on Day 42, beginning with a loading dose of dupilumab (two 300 mg subcutaneous injections \[total of 600 mg\]-protection of prior masking/blind maintained). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
|---|---|---|
|
Pruritus Numerical Rating Scale (Pruritus NRS) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 3
|
5.37 units on a scale
Interval 4.73 to 6.01
|
5.64 units on a scale
Interval 4.83 to 6.45
|
|
Pruritus Numerical Rating Scale (Pruritus NRS) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 7
|
5.46 units on a scale
Interval 4.83 to 6.09
|
5.48 units on a scale
Interval 4.69 to 6.28
|
|
Pruritus Numerical Rating Scale (Pruritus NRS) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 14
|
4.48 units on a scale
Interval 3.91 to 5.05
|
5.29 units on a scale
Interval 4.58 to 6.0
|
|
Pruritus Numerical Rating Scale (Pruritus NRS) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 21
|
4.20 units on a scale
Interval 3.62 to 4.79
|
5.22 units on a scale
Interval 4.5 to 5.93
|
|
Pruritus Numerical Rating Scale (Pruritus NRS) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 28
|
3.67 units on a scale
Interval 3.07 to 4.28
|
5.14 units on a scale
Interval 4.37 to 5.9
|
|
Pruritus Numerical Rating Scale (Pruritus NRS) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 42
|
3.40 units on a scale
Interval 2.79 to 4.01
|
5.18 units on a scale
Interval 4.41 to 5.94
|
|
Pruritus Numerical Rating Scale (Pruritus NRS) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 77
|
2.55 units on a scale
Interval 2.05 to 3.05
|
1.88 units on a scale
Interval 1.28 to 2.48
|
|
Pruritus Numerical Rating Scale (Pruritus NRS) Score Within Each Treatment Group, Dupilumab+Open Label Extension and Follow-Up Versus Placebo+Open Label Extension and Follow-Up
Day 112
|
2.38 units on a scale
Interval 1.83 to 2.94
|
1.95 units on a scale
Interval 1.27 to 2.64
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 0 (Prior to treatment), 16 weeks16S rRNA microbiome data (e.g., bacterial sequence reads) will be employed to identify changes in community composition and diversity at lesional and non-lesional skin sites prior to and throughout dupilumab or placebo treatment.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 0 (Prior to treatment), 16 weeksThe aim is to assess the effect of dupilumab on the skin transcriptome in lesional and non-lesional skin. Inclusion in this exploratory aim is restricted to non-University of Rochester Medical Center study participants only.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 0 (Prior to treatment) and 7The aim is to assess the effect of dupilumab on gene expression in the skin transcriptome of non-lesional skin.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 0 (Prior to treatment), 7, and 21The aim is to assess the effect of dupilumab on the gene expression in the skin transcriptome of lesional skin.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 0 (Prior to treatment), 16 weeksThe aim is to assess the effect of dupilumab on lipids, which play a role in the skin barrier, will be extracted from the skin tape strips and measured using mass spectrometry methodology. Skin tape strip method allows characterization of components of the epidermis, dermis, and immune cells present in the skin.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 0 (Prior to treatment), 16 weeksThe aim is to assess the effect of dupilumab on the expression of the bacterium Staphylococcus aureus (S. aureus) superantigens and toxins on lesional and non-lesional skin.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Days 0 (Prior to treatment), 7 and 21The aim is to assess the effect of dupilumab on non-lesional skin barrier structure and Langerhans cells (LC) by confocal imaging. Inclusion in this exploratory aim is limited to University of Rochester Medical Center study participants.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 0 (Prior to treatment), 16 weeksThe aim is to assess the effect of dupilumab on the function of the skin microbiome (e.g., the ability of Coagulase-negative staphylococci isolates \[CoNS\] to kill S. aureus) in lesional and non-lesional skin.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Days 0 (Prior to treatment), 14 and 28The aim is to assess the effect of dupilumab on PBMC immunoprofiles.Flow cytometry analysis will be performed on PBMCs, using phenotyping panels to identify resting leukocyte populations, as well as T cell responses to antigens and myeloid responses to Toll-like receptor (TLR) ligands.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 0 (Prior to treatment), 16 weeksThe aim is to assess the effect of dupilumab on serum biomarkers (e.g. T helper type 2 \[Th2\] biomarkers).
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 0 (Prior to treatment), 16 weeksThe presence of anti-drug antibodies will be assessed and compared between intervention groups.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 0 (Prior to treatment)Towards discovery and replication of susceptibility loci in atopic dermatitis pathogenesis.
Outcome measures
Outcome data not reported
Adverse Events
Dupilumab+Open Label Extension and Follow-Up
Placebo+Open Label Extension and Follow-Up
Serious adverse events
| Measure |
Dupilumab+Open Label Extension and Follow-Up
n=46 participants at risk
Participants received a loading dose of two 300 mg subcutaneous injections on Day 0 followed by 300 mg subcutaneous injections every two weeks (Days 14 and 28). Participants started a 10 week OLE on Day 42, beginning with a loading dose of two subcutaneously administered injections (one 300 mg dose of dupilumab and one dose of placebo, in order to protect prior masking/blind). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
Placebo+Open Label Extension and Follow-Up
n=26 participants at risk
Placebo contained the identical formulation as the dupilumab formulation without the active monoclonal antibody and was given by exactly the same route and schedule through Day 28. Participants started a 10 week OLE on Day 42, beginning with a loading dose of dupilumab (two 300 mg subcutaneous injections \[total of 600 mg\]-protection of prior masking/blind maintained). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Intentional overdose
|
2.2%
1/46 • Number of events 1 • Up to 182 days
|
0.00%
0/26 • Up to 182 days
|
|
Psychiatric disorders
Schizoaffective disorder bipolar type
|
2.2%
1/46 • Number of events 1 • Up to 182 days
|
0.00%
0/26 • Up to 182 days
|
Other adverse events
| Measure |
Dupilumab+Open Label Extension and Follow-Up
n=46 participants at risk
Participants received a loading dose of two 300 mg subcutaneous injections on Day 0 followed by 300 mg subcutaneous injections every two weeks (Days 14 and 28). Participants started a 10 week OLE on Day 42, beginning with a loading dose of two subcutaneously administered injections (one 300 mg dose of dupilumab and one dose of placebo, in order to protect prior masking/blind). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
Placebo+Open Label Extension and Follow-Up
n=26 participants at risk
Placebo contained the identical formulation as the dupilumab formulation without the active monoclonal antibody and was given by exactly the same route and schedule through Day 28. Participants started a 10 week OLE on Day 42, beginning with a loading dose of dupilumab (two 300 mg subcutaneous injections \[total of 600 mg\]-protection of prior masking/blind maintained). Participants then maintained a regimen of 300 mg of dupilumab by subcutaneous injection every two weeks through Day 98. The participants then entered a follow-up period until Day 182.
|
|---|---|---|
|
Eye disorders
Conjunctivitis allergic
|
2.2%
1/46 • Number of events 1 • Up to 182 days
|
7.7%
2/26 • Number of events 2 • Up to 182 days
|
|
Eye disorders
Dry eye
|
8.7%
4/46 • Number of events 6 • Up to 182 days
|
3.8%
1/26 • Number of events 1 • Up to 182 days
|
|
Gastrointestinal disorders
Nausea
|
6.5%
3/46 • Number of events 3 • Up to 182 days
|
0.00%
0/26 • Up to 182 days
|
|
Infections and infestations
Conjunctivitis
|
8.7%
4/46 • Number of events 4 • Up to 182 days
|
11.5%
3/26 • Number of events 3 • Up to 182 days
|
|
Infections and infestations
Furuncle
|
0.00%
0/46 • Up to 182 days
|
7.7%
2/26 • Number of events 2 • Up to 182 days
|
|
Infections and infestations
Nasopharyngitis
|
13.0%
6/46 • Number of events 7 • Up to 182 days
|
7.7%
2/26 • Number of events 3 • Up to 182 days
|
|
Infections and infestations
Upper respiratory tract infection
|
15.2%
7/46 • Number of events 10 • Up to 182 days
|
11.5%
3/26 • Number of events 3 • Up to 182 days
|
|
Injury, poisoning and procedural complications
Fall
|
2.2%
1/46 • Number of events 1 • Up to 182 days
|
11.5%
3/26 • Number of events 3 • Up to 182 days
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
2.2%
1/46 • Number of events 1 • Up to 182 days
|
11.5%
3/26 • Number of events 3 • Up to 182 days
|
|
Nervous system disorders
Headache
|
2.2%
1/46 • Number of events 1 • Up to 182 days
|
15.4%
4/26 • Number of events 6 • Up to 182 days
|
|
Skin and subcutaneous tissue disorders
Dermatitis atopic
|
15.2%
7/46 • Number of events 16 • Up to 182 days
|
26.9%
7/26 • Number of events 11 • Up to 182 days
|
|
Skin and subcutaneous tissue disorders
Eczema
|
26.1%
12/46 • Number of events 12 • Up to 182 days
|
19.2%
5/26 • Number of events 7 • Up to 182 days
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.7%
4/46 • Number of events 4 • Up to 182 days
|
11.5%
3/26 • Number of events 4 • Up to 182 days
|
Additional Information
Director, Clinical Research Operations Program
DAIT/NIAID
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place