Trial Outcomes & Findings for Efficacy and Safety Study of the Use of Benralizumab for Patients With Moderate to Severe Atopic Dermatitis (NCT NCT04605094)
NCT ID: NCT04605094
Last Updated: 2023-08-31
Results Overview
The IGA is an instrument used in clinical studies to rate the severity of AD globally, based on a 5-point scale ranging from 0 = clear; 1 = almost clear; 2 = mild disease; 3 = moderate disease; 4 = severe disease. The IGA used clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity assessment. A higher score indicated greater severity. A responder at Week 16 was defined as having IGA 0/1 and a decrease in IGA of ≥2 points at Week 16 relative to baseline. Participants who withdrew from the study/required rescue therapy after Day 28 were considered as non-responders from the time these events occurred. Baseline was defined as the last recorded value on or prior to the date of randomization.
TERMINATED
PHASE2
194 participants
Baseline (Week 0) and at Week 16
2023-08-31
Participant Flow
This Phase 2, double-blind, placebo-controlled study was conducted in participants with moderate to severe atopic dermatitis (AD) at 48 study centers in 8 countries.
This study consisted of a screening period (up to 4 weeks), placebo-controlled double-blind treatment period (up to 16 weeks) and an extension period (up to 36 weeks). A total of 194 participants were randomized and received treatment in this study.
Participant milestones
| Measure |
Benralizumab
Participants received benralizumab 30 milligram (mg) subcutaneous (SC) injection on Day 1 visit for every 4 weeks (Q4W) until Week 16 visit. In extension phase, participants received benralizumab 30 mg SC injection for either Q4W or every 8 weeks (Q8W) until Week 52 visit.
|
Placebo
Participants received placebo matching benralizumab on Day 1 visit for Q4W until Week 16. In extension phase, participants received benralizumab 30 mg SC injection for Q4W until Week 28 visit and then followed by benralizumab 30 mg SC injection for Q8W until Week 52 visit.
|
|---|---|---|
|
Overall Study
STARTED
|
96
|
98
|
|
Overall Study
COMPLETED
|
37
|
37
|
|
Overall Study
NOT COMPLETED
|
59
|
61
|
Reasons for withdrawal
| Measure |
Benralizumab
Participants received benralizumab 30 milligram (mg) subcutaneous (SC) injection on Day 1 visit for every 4 weeks (Q4W) until Week 16 visit. In extension phase, participants received benralizumab 30 mg SC injection for either Q4W or every 8 weeks (Q8W) until Week 52 visit.
|
Placebo
Participants received placebo matching benralizumab on Day 1 visit for Q4W until Week 16. In extension phase, participants received benralizumab 30 mg SC injection for Q4W until Week 28 visit and then followed by benralizumab 30 mg SC injection for Q8W until Week 52 visit.
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
4
|
|
Overall Study
Physician Decision
|
2
|
2
|
|
Overall Study
Study terminated by Sponsor
|
31
|
33
|
|
Overall Study
Withdrawal by Subject
|
22
|
19
|
|
Overall Study
Other
|
1
|
1
|
Baseline Characteristics
Efficacy and Safety Study of the Use of Benralizumab for Patients With Moderate to Severe Atopic Dermatitis
Baseline characteristics by cohort
| Measure |
Benralizumab
n=96 Participants
Participants received benralizumab 30 mg SC injection on Day 1 visit for Q4W until Week 16 visit. In extension phase, participants received benralizumab 30 mg SC injection for either Q4W or Q8W until Week 52 visit.
|
Placebo
n=98 Participants
Participants received placebo matching benralizumab on Day 1 visit for Q4W until Week 16. In extension phase, participants received benralizumab 30 mg SC injection for Q4W until Week 28 visit and then followed by benralizumab 30 mg SC injection for Q8W until Week 52 visit.
|
Total
n=194 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
29.8 years
STANDARD_DEVIATION 15.87 • n=5 Participants
|
29.5 years
STANDARD_DEVIATION 16.00 • n=7 Participants
|
29.6 years
STANDARD_DEVIATION 15.90 • n=5 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
72 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
56 Participants
n=5 Participants
|
66 Participants
n=7 Participants
|
122 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
24 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
65 Participants
n=5 Participants
|
70 Participants
n=7 Participants
|
135 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
11 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
85 Participants
n=5 Participants
|
85 Participants
n=7 Participants
|
170 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (Week 0) and at Week 16Population: The FAS consisted of all randomized participants who received at least 1 dose of study drug, irrespective of their protocol adherence and continued participation in the study.
The IGA is an instrument used in clinical studies to rate the severity of AD globally, based on a 5-point scale ranging from 0 = clear; 1 = almost clear; 2 = mild disease; 3 = moderate disease; 4 = severe disease. The IGA used clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity assessment. A higher score indicated greater severity. A responder at Week 16 was defined as having IGA 0/1 and a decrease in IGA of ≥2 points at Week 16 relative to baseline. Participants who withdrew from the study/required rescue therapy after Day 28 were considered as non-responders from the time these events occurred. Baseline was defined as the last recorded value on or prior to the date of randomization.
Outcome measures
| Measure |
Benralizumab
n=96 Participants
Participants received benralizumab 30 mg SC injection on Day 1 visit for Q4W until Week 16 visit. In extension phase, participants received benralizumab 30 mg SC injection for either Q4W or Q8W until Week 52 visit.
|
Placebo
n=98 Participants
Participants received placebo matching benralizumab on Day 1 visit for Q4W until Week 16. In extension phase, participants received benralizumab 30 mg SC injection for Q4W until Week 28 visit and then followed by benralizumab 30 mg SC injection for Q8W until Week 52 visit.
|
|---|---|---|
|
Percentage of Participants With an Investigator Global Assessment (IGA) 0/1 and a Decrease in IGA of ≥2 Points at Week 16 Relative to Baseline
|
9.4 percentage of participants
Interval 3.36 to 14.93
|
17.3 percentage of participants
Interval 10.4 to 25.12
|
SECONDARY outcome
Timeframe: Baseline (Week 0) and at Week 16Population: The FAS consisted of all randomized participants who received at least 1 dose of study drug, irrespective of their protocol adherence and continued participation in the study.
The EASI assessed the severity and extent of AD. Severity of 4 AD disease characteristics (erythema, induration/papulation, excoriation \[scratching\], lichenification) each were assessed on a scale of 0 (absent) to 3 (severe) in each of 4 body regions (head/neck, trunk, upper limbs, and lower limbs). Total body total score=sum of the region total scores; ranged from 0 to 72. Participants were classified as responders if they achieved at least 75% reduction from baseline in their EASI total score at Week 16. Participants who withdrew from study/required rescue therapy after Day 28 were non-responders from the time these events occurred. Higher scores indicated a more severe or more extensive condition. Baseline was defined as the last recorded value on or prior to the date of randomization.
Outcome measures
| Measure |
Benralizumab
n=96 Participants
Participants received benralizumab 30 mg SC injection on Day 1 visit for Q4W until Week 16 visit. In extension phase, participants received benralizumab 30 mg SC injection for either Q4W or Q8W until Week 52 visit.
|
Placebo
n=98 Participants
Participants received placebo matching benralizumab on Day 1 visit for Q4W until Week 16. In extension phase, participants received benralizumab 30 mg SC injection for Q4W until Week 28 visit and then followed by benralizumab 30 mg SC injection for Q8W until Week 52 visit.
|
|---|---|---|
|
Percentage of Participants Who Experienced 75% Reduction From Baseline in Eczema Area and Severity Index (EASI-75) at Week 16
|
19.8 percentage of participants
Interval 11.71 to 27.45
|
24.5 percentage of participants
Interval 16.27 to 33.19
|
SECONDARY outcome
Timeframe: Baseline (Week 0) and at Week 16Population: The FAS consisted of all randomized participants who received at least 1 dose of study drug, irrespective of their protocol adherence and continued participation in the study.
The EASI assessed the severity and extent of AD. Severity of 4 AD disease characteristics (erythema, induration/papulation, excoriation \[scratching\], lichenification) each were assessed on a scale of 0 (absent) to 3 (severe) in each of 4 body regions (head/neck, trunk, upper limbs, and lower limbs). Total body total score=sum of the region total scores; ranged from 0 to 72. Participants were classified as responders if they achieved at least 90% reduction from baseline in their EASI total score at Week 16. Participants who withdrew from study/required rescue therapy after Day 28 were non-responders from the time these events occurred. Higher scores indicated a more severe or more extensive condition. Baseline was defined as the last recorded value on or prior to the date of randomization.
Outcome measures
| Measure |
Benralizumab
n=96 Participants
Participants received benralizumab 30 mg SC injection on Day 1 visit for Q4W until Week 16 visit. In extension phase, participants received benralizumab 30 mg SC injection for either Q4W or Q8W until Week 52 visit.
|
Placebo
n=98 Participants
Participants received placebo matching benralizumab on Day 1 visit for Q4W until Week 16. In extension phase, participants received benralizumab 30 mg SC injection for Q4W until Week 28 visit and then followed by benralizumab 30 mg SC injection for Q8W until Week 52 visit.
|
|---|---|---|
|
Percentage of Participants Who Experienced 90% Reduction From Baseline in Eczema Area and Severity Index (EASI-90) at Week 16
|
7.3 percentage of participants
Interval 2.05 to 12.42
|
15.3 percentage of participants
Interval 8.33 to 22.5
|
SECONDARY outcome
Timeframe: At Week 16Population: The FAS consisted of all randomized participants who received at least 1 dose of study drug, irrespective of their protocol adherence and continued participation in the study.
The peak pruritus numeric rating scale (NRS) was a 1-item daily assessment of the worst itch the participant experienced over the past 24 hours. The score ranged from 0 to 10, with 0 being "no itch" and 10 being "worst itch imaginable" and so a reduction in score was considered an improvement. A responder was defined as having an improvement of 4 or more points relative to baseline. Participants who withdrew from the study/required rescue therapy after Day 28 were considered as non-responders from the time these events occurred. The Week 16 weekly scores were defined as the average of the daily scores for the 7 days prior to the weekly score.
Outcome measures
| Measure |
Benralizumab
n=96 Participants
Participants received benralizumab 30 mg SC injection on Day 1 visit for Q4W until Week 16 visit. In extension phase, participants received benralizumab 30 mg SC injection for either Q4W or Q8W until Week 52 visit.
|
Placebo
n=98 Participants
Participants received placebo matching benralizumab on Day 1 visit for Q4W until Week 16. In extension phase, participants received benralizumab 30 mg SC injection for Q4W until Week 28 visit and then followed by benralizumab 30 mg SC injection for Q8W until Week 52 visit.
|
|---|---|---|
|
Percentage of Participants With an Improvement of ≥4 or More Points in Peak Pruritus Weekly Score
|
14.6 percentage of participants
Interval 7.87 to 21.7
|
14.3 percentage of participants
Interval 7.28 to 20.9
|
Adverse Events
Benralizumab
Placebo
Placebo to Benralizumab
Serious adverse events
| Measure |
Benralizumab
n=96 participants at risk
Participants received benralizumab 30 mg SC injection on Day 1 visit for Q4W until Week 16 visit. In extension phase, participants received benralizumab 30 mg SC injection for either Q4W or Q8W until Week 52 visit.
|
Placebo
n=98 participants at risk
Participants received placebo matching benralizumab on Day 1 visit for Q4W until Week 16 in placebo-controlled treatment period.
|
Placebo to Benralizumab
n=87 participants at risk
Participants who completed placebo-controlled treatment period entered extension phase. Participants received benralizumab 30 mg SC injection for Q4W until Week 28 visit and then followed by benralizumab 30 mg SC injection for Q8W until Week 52 visit.
|
|---|---|---|---|
|
Cardiac disorders
Cardiac failure congestive
|
1.0%
1/96 • Number of events 1 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
0.00%
0/98 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
0.00%
0/87 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hodgkin's disease
|
0.00%
0/96 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
0.00%
0/98 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
1.1%
1/87 • Number of events 1 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Migraine
|
0.00%
0/96 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
0.00%
0/98 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
1.1%
1/87 • Number of events 1 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Paranasal sinus inflammation
|
1.0%
1/96 • Number of events 1 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
0.00%
0/98 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
0.00%
0/87 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Dermatitis atopic
|
1.0%
1/96 • Number of events 2 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
0.00%
0/98 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
0.00%
0/87 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
Other adverse events
| Measure |
Benralizumab
n=96 participants at risk
Participants received benralizumab 30 mg SC injection on Day 1 visit for Q4W until Week 16 visit. In extension phase, participants received benralizumab 30 mg SC injection for either Q4W or Q8W until Week 52 visit.
|
Placebo
n=98 participants at risk
Participants received placebo matching benralizumab on Day 1 visit for Q4W until Week 16 in placebo-controlled treatment period.
|
Placebo to Benralizumab
n=87 participants at risk
Participants who completed placebo-controlled treatment period entered extension phase. Participants received benralizumab 30 mg SC injection for Q4W until Week 28 visit and then followed by benralizumab 30 mg SC injection for Q8W until Week 52 visit.
|
|---|---|---|---|
|
Infections and infestations
Bronchitis
|
5.2%
5/96 • Number of events 5 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
0.00%
0/98 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
4.6%
4/87 • Number of events 4 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
|
Infections and infestations
Conjunctivitis
|
3.1%
3/96 • Number of events 4 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
0.00%
0/98 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
6.9%
6/87 • Number of events 6 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
|
Infections and infestations
COVID-19
|
21.9%
21/96 • Number of events 23 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
4.1%
4/98 • Number of events 4 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
16.1%
14/87 • Number of events 14 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
9.4%
9/96 • Number of events 10 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
0.00%
0/98 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
8.0%
7/87 • Number of events 8 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
|
Infections and infestations
Upper respiratory tract infection
|
9.4%
9/96 • Number of events 12 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
2.0%
2/98 • Number of events 3 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
5.7%
5/87 • Number of events 5 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
4.2%
4/96 • Number of events 4 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
5.1%
5/98 • Number of events 8 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
0.00%
0/87 • Adverse events in the on-study period were reported from the first dose of study treatment (Day 1) up to end of follow-up, approximately a maximum up to Week 60
The Safety Analysis set consisted of all participants who received at least 1 dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place