Dermatitis, Atopic
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled, parallel group study to confirm the efficacy and safety of Dupilumab monotherapy in adults with moderate-to-severe atopic dermatitis (AD).
Interventions
DRUGDupilumab
Subcutaneous injection alternated among the different quadrants of the abdomen, upper thighs and upper arms
Subcutaneous injection alternated among the different quadrants of the abdomen, upper thighs and upper arms
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female, 18 years or older 2. Chronic AD (according to American Academy of Dermatology Consensus Criteria Eichenfield 2014) that has been present for at least 3 years before the screening visit; 3. Eczema Area and Severity Index (EASI) Score ≥16 at the screening and baseline visits; 4. Investigator's Global Assessment (IGA) Score ≥3 (on the 0 to 4 IGA scale, in which 3 is moderate and 4 is severe) at the screening and baseline visits; 5. ≥10% body surface area (BSA) of AD involvement at the screening and baseline visits; 6. Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable (e.g, because of important side effects or safety risks).
Exclusion criteria
1. Participation in a prior Dupilumab clinical study; 2. Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known), whichever was longer, before the baseline visit; 3. Having used any of the following treatments within 4 weeks before the baseline visit, or any condition that, in the opinion of the investigator, was likely to require such treatment(s) during the first 4 weeks of study treatment: * Immunosuppressive/ immunomodulating drugs (e.g, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc.); * Phototherapy for AD 4. Treatment with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) within 1 week before the baseline visit; 5. Treatment with biologics as follows: * Any cell-depleting agents including but not limited to rituximab: within 6 months before the baseline visit, or until lymphocyte count returns to normal, whichever was longer * Other biologics: within 5 half-lives (if known) or 16 weeks prior to baseline visit, whichever was longer 6. Regular use (more than 2 visits per week) of a tanning booth/ parlor within 4 weeks of the screening visit; 7. Planned or anticipated use of any prohibited medications and procedures during study treatment; 8. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit; 9. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit, or superficial skin infections within 1 week before the baseline visit. NOTE: Participants might be rescreened after infection resolves; 10. Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g, tuberculosis \[TB\], histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution: or unusually frequent, recurrent, or prolonged infections, per investigator judgment; 11. History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening; 12. Positive with hepatitis B surface antigen (HBsAg) or hepatitis C antibody at the screening visit; 13. Participant was a member of the investigational team or his/her immediate family; 14. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study; 15. Women unwilling to use adequate birth control, if of reproductive potential and sexually active. Note: The information listed above is not intended to contain all considerations relevant to a participant's potential participation in this clinical trial therefore not all inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Investigator's Global Assessment (IGA) Score of 0 or 1 and Reduction From Baseline of ≥2 Points at Week 16 | Week 16 | IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score of 0 or 1 and a reduction from baseline of ≥2 points at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 16 were considered as non-responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16 | Baseline to Week 16 | Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were considered as non-responders. |
| Percentage of Participants With Improvement (Reduction ≥3 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16 | Baseline to Week 16 | Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Participants achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were considered as non-responders. |
| Percent Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16 | Baseline to Week 16 | Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). |
| Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 4 | Baseline to Week 4 | Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 4 were reported. Values after first rescue treatment were set to missing and subjects with missing peak NRS at Week 4 were considered as non-responders. |
| Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 2 | Baseline to Week 2 | Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 2 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 2 were considered as non-responders. |
| Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16 | Baseline to Week 16 | Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). |
| Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 16 | Baseline to Week 16 | The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. |
| Percentage of Participants With Eczema Area and Severity Index-50 (EASI-50) (≥50% Improvement From Baseline) at Week 16 | Week 16 | The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50 responders were the participants who achieved ≥50% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing EASI-50 scores at Week 16 were considered as non-responders. |
| Percentage of Participants With Eczema Area and Severity Index-90 (EASI-90) (≥90% Improvement From Baseline) at Week 16 | Week 16 | The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-90 responders were the participants who achieved ≥90% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing EASI-90 scores at Week 16 were considered as non-responders. |
| Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16 | Week 16 | The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 16 were considered as non-responders. |
| Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 16 | Baseline to Week 16 | SCORAD is a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). |
| Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16 | Baseline to Week 16 | The DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The 10 questions assessed QOL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score was indicative of a poor QOL. |
| Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16 | Baseline to Week 16 | The POEM is a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life \[QOL\]). |
| Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16 | Baseline to Week 16 | HADS is a fourteen item scale. Seven of the items relate to anxiety and seven items relate to depression. Each item on the questionnaire is scored from 0 (minimum score) - 3 (maximum score) and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported as 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression. |
| Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) Requiring Systemic Treatment | Baseline up to Week 16 | Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study \[Week 28\]). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. Statistical significance in the hierarchical testing of secondary hypotheses was broken at this endpoint. Therefore, subsequent secondary efficacy endpoints were not tested for statistical significance. |
| Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 16 | Baseline to Week 16 | Individual components of the AD lesions (erythema, infiltration/ papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0= none, 1= mild, 2= moderate and 3= severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease). |
| Percent Change From Baseline in Peak Daily Pruritus NRS Score to Week 2 | Baseline to Week 2 | Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). |
| Percentage of Participants With Treatment Emergent Serious Adverse Events (TESAEs) From Baseline Through Week 16 | Baseline up to Week 16 | Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study \[Week 28\]). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. |
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Treatment Discontinuation From Baseline Through Week 16 | Baseline up to Week 16 | Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study \[Week 28\]). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. |
| Change From Baseline in Percent Body Surface Area (BSA) to Week 16 | Baseline to Week 16 | BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck \[9%\], anterior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], and genitals \[1%\]). It was reported as a percentage of all major body sections combined. |
Countries
Bulgaria, Canada, Denmark, Estonia, Finland, Germany, Japan, Singapore, Spain, United States
Participant flow
Recruitment details
The study was conducted in 10 countries between 28 Oct 2014 and 12 Feb 2016. A total of 917 participants were screened in the study.
Pre-assignment details
Out of 917 participants, 671 were randomized and 669 were treated in the study. Participants were randomized in 1:1:1 ratio to receive Dupilumab 300 mg once weekly (qw), Dupilumab 300 mg every 2 weeks (q2w) or Placebo qw.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15. | 224 |
| Dupilumab 300 mg q2w Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a placebo alternating with single 300 mg injection of Dupilumab qw from Week 1 to Week 15. | 224 |
| Dupilumab 300 mg qw Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab qw from Week 1 to Week 15. | 223 |
| Total | 671 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 10 | 6 | 6 |
| Overall Study | Lack of Efficacy | 11 | 4 | 3 |
| Overall Study | Other than specified above | 18 | 5 | 16 |
| Overall Study | Protocol Violation | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Dupilumab 300 mg qw | Dupilumab 300 mg q2w |
|---|---|---|---|---|
| Age, Continuous | 39.5 years STANDARD_DEVIATION 13.91 | 39.5 years STANDARD_DEVIATION 14.31 | 39.3 years STANDARD_DEVIATION 14.39 | 39.8 years STANDARD_DEVIATION 14.68 |
| Body Surface Area (BSA) Involvement with AD | 57.5 percentage of body surface area STANDARD_DEVIATION 23.38 | 56.1 percentage of body surface area STANDARD_DEVIATION 23.17 | 56.1 percentage of body surface area STANDARD_DEVIATION 22.96 | 54.7 percentage of body surface area STANDARD_DEVIATION 23.19 |
| Dermatology Life Quality Index (DLQI) Score | 14.8 units on a scale STANDARD_DEVIATION 7.23 | 14.2 units on a scale STANDARD_DEVIATION 7.37 | 14.1 units on a scale STANDARD_DEVIATION 7.51 | 13.9 units on a scale STANDARD_DEVIATION 7.37 |
| Eczema Area and Severity Index (EASI) Score | 34.5 units on scale STANDARD_DEVIATION 14.47 | 33.6 units on scale STANDARD_DEVIATION 14 | 33.2 units on scale STANDARD_DEVIATION 13.98 | 33 units on scale STANDARD_DEVIATION 13.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 25 Participants | 8 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 212 Participants | 639 Participants | 212 Participants | 215 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 7 Participants | 3 Participants | 3 Participants |
| Global Individual Signs Score (GISS) | 9.0 units on a scale STANDARD_DEVIATION 1.85 | 9.0 units on a scale STANDARD_DEVIATION 1.8 | 8.9 units on a scale STANDARD_DEVIATION 1.74 | 8.9 units on a scale STANDARD_DEVIATION 1.81 |
| Investigator's Global Assessment (IGA) Score | 3.5 units on a scale STANDARD_DEVIATION 0.5 | 3.5 units on a scale STANDARD_DEVIATION 0.5 | 3.5 units on a scale STANDARD_DEVIATION 0.5 | 3.5 units on a scale STANDARD_DEVIATION 0.5 |
| Patient Oriented Eczema Measure (POEM) | 20.3 units on a scale STANDARD_DEVIATION 5.9 | 20.1 units on a scale STANDARD_DEVIATION 6.17 | 20.4 units on a scale STANDARD_DEVIATION 6.25 | 19.8 units on a scale STANDARD_DEVIATION 6.37 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 56 Participants | 161 Participants | 51 Participants | 54 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 46 Participants | 20 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 14 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) White | 146 Participants | 450 Participants | 149 Participants | 155 Participants |
| Region of Enrollment Asia Pacific | 40 Participants | 120 Participants | 38 Participants | 42 Participants |
| Region of Enrollment Eastern Europe | 23 Participants | 69 Participants | 24 Participants | 22 Participants |
| Region of Enrollment North and South America | 95 Participants | 286 Participants | 96 Participants | 95 Participants |
| Region of Enrollment Western Europe | 66 Participants | 196 Participants | 65 Participants | 65 Participants |
| SCORing Atopic Dermatitis (SCORAD) Score | 68.3 units on a scale STANDARD_DEVIATION 13.96 | 67.6 units on a scale STANDARD_DEVIATION 13.84 | 67.5 units on a scale STANDARD_DEVIATION 13.61 | 66.9 units on a scale STANDARD_DEVIATION 13.97 |
| Sex: Female, Male Female | 106 Participants | 281 Participants | 81 Participants | 94 Participants |
| Sex: Female, Male Male | 118 Participants | 390 Participants | 142 Participants | 130 Participants |
| Total Hospital Anxiety Depression Scale (HADS) | 12.6 units on a scale STANDARD_DEVIATION 8.33 | 12.5 units on a scale STANDARD_DEVIATION 7.85 | 12.6 units on a scale STANDARD_DEVIATION 7.95 | 12.2 units on a scale STANDARD_DEVIATION 7.26 |
| Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) | 7.4 units on a scale STANDARD_DEVIATION 1.77 | 7.3 units on a scale STANDARD_DEVIATION 1.91 | 7.2 units on a scale STANDARD_DEVIATION 2.06 | 7.2 units on a scale STANDARD_DEVIATION 1.89 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 222 | 0 / 229 | 0 / 218 |
| other Total, other adverse events | 97 / 222 | 92 / 229 | 90 / 218 |
| serious Total, serious adverse events | 12 / 222 | 7 / 229 | 2 / 218 |
Outcome results
Primary
Percentage of Participants With Investigator's Global Assessment (IGA) Score of 0 or 1 and Reduction From Baseline of ≥2 Points at Week 16
IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score of 0 or 1 and a reduction from baseline of ≥2 points at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 16 were considered as non-responders.
Time frame: Week 16
Population: Full analysis set included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Investigator's Global Assessment (IGA) Score of 0 or 1 and Reduction From Baseline of ≥2 Points at Week 16 | 10.3 percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants With Investigator's Global Assessment (IGA) Score of 0 or 1 and Reduction From Baseline of ≥2 Points at Week 16 | 37.9 percentage of participants |
| Dupilumab 300 mg qw | Percentage of Participants With Investigator's Global Assessment (IGA) Score of 0 or 1 and Reduction From Baseline of ≥2 Points at Week 16 | 37.2 percentage of participants |
Comparison: Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity.p-value: <0.000195% CI: [20.18, 35.17]Cochran-Mantel-Haenszel
Comparison: Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity.p-value: <0.000195% CI: [19.47, 34.44]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16
The DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The 10 questions assessed QOL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score was indicative of a poor QOL.
Time frame: Baseline to Week 16
Population: Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16 | -5.6 units on a scale | Standard Deviation 5.86 |
| Dupilumab 300 mg q2w | Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16 | -9.0 units on a scale | Standard Deviation 6.61 |
| Dupilumab 300 mg qw | Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16 | -8.8 units on a scale | Standard Deviation 6.79 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [-5.16, -2.8]ANCOVA
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [-4.87, -2.49]ANCOVA
Secondary
Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16
HADS is a fourteen item scale. Seven of the items relate to anxiety and seven items relate to depression. Each item on the questionnaire is scored from 0 (minimum score) - 3 (maximum score) and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported as 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression.
Time frame: Baseline to Week 16
Population: Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16 | -2.7 units on a scale | Standard Deviation 4.4 |
| Dupilumab 300 mg q2w | Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16 | -4.8 units on a scale | Standard Deviation 5.5 |
| Dupilumab 300 mg qw | Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16 | -4.9 units on a scale | Standard Deviation 5.36 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: 0.000695% CI: [-3.44, -0.95]ANCOVA
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: 0.000395% CI: [-3.46, -1.03]ANCOVA
Secondary
Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16
The POEM is a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life \[QOL\]).
Time frame: Baseline to Week 16
Population: Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16 | -5.3 units on a scale | Standard Deviation 6.24 |
| Dupilumab 300 mg q2w | Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16 | -11.5 units on a scale | Standard Deviation 7.07 |
| Dupilumab 300 mg qw | Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16 | -11.3 units on a scale | Standard Deviation 6.36 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-8.02, -5.01]ANCOVA
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [-7.44, -4.32]ANCOVA
Secondary
Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16
Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]).
Time frame: Baseline to Week 16
Population: Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16 | -2.13 units on a scale | Standard Deviation 2.044 |
| Dupilumab 300 mg q2w | Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16 | -3.78 units on a scale | Standard Deviation 2.325 |
| Dupilumab 300 mg qw | Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16 | -3.72 units on a scale | Standard Deviation 2.186 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [-2.236, -1.26]ANCOVA
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [-2.189, -1.186]ANCOVA
Secondary
Change From Baseline in Percent Body Surface Area (BSA) to Week 16
BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck \[9%\], anterior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], and genitals \[1%\]). It was reported as a percentage of all major body sections combined.
Time frame: Baseline to Week 16
Population: Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Percent Body Surface Area (BSA) to Week 16 | -17.2 percentage of body surface area | Standard Deviation 17.381 |
| Dupilumab 300 mg q2w | Change From Baseline in Percent Body Surface Area (BSA) to Week 16 | -33.72 percentage of body surface area | Standard Deviation 19.619 |
| Dupilumab 300 mg qw | Change From Baseline in Percent Body Surface Area (BSA) to Week 16 | -35.42 percentage of body surface area | Standard Deviation 19.926 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [-22.487, -13.353]ANCOVA
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [-23.125, -14.65]ANCOVA
Secondary
Percentage of Participants With Eczema Area and Severity Index-50 (EASI-50) (≥50% Improvement From Baseline) at Week 16
The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50 responders were the participants who achieved ≥50% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing EASI-50 scores at Week 16 were considered as non-responders.
Time frame: Week 16
Population: Full analysis set (FAS) included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Eczema Area and Severity Index-50 (EASI-50) (≥50% Improvement From Baseline) at Week 16 | 24.6 percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants With Eczema Area and Severity Index-50 (EASI-50) (≥50% Improvement From Baseline) at Week 16 | 68.8 percentage of participants |
| Dupilumab 300 mg qw | Percentage of Participants With Eczema Area and Severity Index-50 (EASI-50) (≥50% Improvement From Baseline) at Week 16 | 61.0 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [35.91, 52.48]Cochran-Mantel-Haenszel
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [27.9, 44.96]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16
The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 16 were considered as non-responders.
Time frame: Week 16
Population: Full analysis set (FAS) included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16 | 14.7 percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16 | 51.3 percentage of participants |
| Dupilumab 300 mg qw | Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16 | 52.5 percentage of participants |
Comparison: A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.025 level. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity.p-value: <0.000195% CI: [28.58, 44.63]Cochran-Mantel-Haenszel
Comparison: A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.025 level. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity.p-value: <0.000195% CI: [29.7, 45.77]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Eczema Area and Severity Index-90 (EASI-90) (≥90% Improvement From Baseline) at Week 16
The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-90 responders were the participants who achieved ≥90% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing EASI-90 scores at Week 16 were considered as non-responders.
Time frame: Week 16
Population: Full analysis set (FAS) included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Eczema Area and Severity Index-90 (EASI-90) (≥90% Improvement From Baseline) at Week 16 | 7.6 percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants With Eczema Area and Severity Index-90 (EASI-90) (≥90% Improvement From Baseline) at Week 16 | 35.7 percentage of participants |
| Dupilumab 300 mg qw | Percentage of Participants With Eczema Area and Severity Index-90 (EASI-90) (≥90% Improvement From Baseline) at Week 16 | 33.2 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [20.96, 35.29]Cochran-Mantel-Haenszel
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [18.51, 32.68]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Improvement (Reduction ≥3 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16
Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Participants achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were considered as non-responders.
Time frame: Baseline to Week 16
Population: Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥3.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Improvement (Reduction ≥3 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16 | 17.2 percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants With Improvement (Reduction ≥3 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16 | 46.8 percentage of participants |
| Dupilumab 300 mg qw | Percentage of Participants With Improvement (Reduction ≥3 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16 | 51.7 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [21.36, 37.88]Cochran-Mantel-Haenszel
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [26.08, 42.84]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16
Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were considered as non-responders.
Time frame: Baseline to Week 16
Population: Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16 | 12.3 percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16 | 40.8 percentage of participants |
| Dupilumab 300 mg qw | Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16 | 40.3 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [20.64, 36.52]Cochran-Mantel-Haenszel
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [19.94, 36.13]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 2
Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 2 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 2 were considered as non-responders.
Time frame: Baseline to Week 2
Population: Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 2 | 3.3 percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 2 | 9.4 percentage of participants |
| Dupilumab 300 mg qw | Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 2 | 9.5 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: 0.009795% CI: [1.49, 10.68]Cochran-Mantel-Haenszel
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: 0.009495% CI: [1.45, 10.86]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 4
Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 4 were reported. Values after first rescue treatment were set to missing and subjects with missing peak NRS at Week 4 were considered as non-responders.
Time frame: Baseline to Week 4
Population: Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 4 | 6.1 percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 4 | 16.0 percentage of participants |
| Dupilumab 300 mg qw | Percentage of Participants With Improvement (Reduction ≥4 Points) of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 4 | 23.4 percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: 0.001295% CI: [3.95, 15.71]Cochran-Mantel-Haenszel
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [10.57, 23.93]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) Requiring Systemic Treatment
Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study \[Week 28\]). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. Statistical significance in the hierarchical testing of secondary hypotheses was broken at this endpoint. Therefore, subsequent secondary efficacy endpoints were not tested for statistical significance.
Time frame: Baseline up to Week 16
Population: Safety analysis set (SAF) which included all randomized participants who received any study drug, and was analyzed as treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) Requiring Systemic Treatment | 0 percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) Requiring Systemic Treatment | 0 percentage of participants |
| Dupilumab 300 mg qw | Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) Requiring Systemic Treatment | 0 percentage of participants |
Secondary
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Treatment Discontinuation From Baseline Through Week 16
Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study \[Week 28\]). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.
Time frame: Baseline up to Week 16
Population: Safety analysis set (SAF) which included all randomized participants who received any study drug, and was analyzed as treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Treatment Discontinuation From Baseline Through Week 16 | 0.9 percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Treatment Discontinuation From Baseline Through Week 16 | 1.7 percentage of participants |
| Dupilumab 300 mg qw | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Treatment Discontinuation From Baseline Through Week 16 | 1.8 percentage of participants |
Secondary
Percentage of Participants With Treatment Emergent Serious Adverse Events (TESAEs) From Baseline Through Week 16
Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study \[Week 28\]). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.
Time frame: Baseline up to Week 16
Population: Safety analysis set (SAF) which included all randomized participants who received any study drug, and was analyzed as treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Treatment Emergent Serious Adverse Events (TESAEs) From Baseline Through Week 16 | 5.0 percentage of participants |
| Dupilumab 300 mg q2w | Percentage of Participants With Treatment Emergent Serious Adverse Events (TESAEs) From Baseline Through Week 16 | 3.1 percentage of participants |
| Dupilumab 300 mg qw | Percentage of Participants With Treatment Emergent Serious Adverse Events (TESAEs) From Baseline Through Week 16 | 0.9 percentage of participants |
Secondary
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 16
The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD.
Time frame: Baseline to Week 16
Population: Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 16 | -39.5 percent change | Standard Deviation 33.66 |
| Dupilumab 300 mg q2w | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 16 | -73.9 percent change | Standard Deviation 26.28 |
| Dupilumab 300 mg qw | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 16 | -73.8 percent change | Standard Deviation 26.41 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [-42.35, -26.88]ANCOVA
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [-42.17, -26.56]ANCOVA
Secondary
Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 16
Individual components of the AD lesions (erythema, infiltration/ papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0= none, 1= mild, 2= moderate and 3= severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease).
Time frame: Baseline to Week 16
Population: Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 16 | -26.2 percent change | Standard Deviation 25.7 |
| Dupilumab 300 mg q2w | Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 16 | -52.5 percent change | Standard Deviation 27.33 |
| Dupilumab 300 mg qw | Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 16 | -51.1 percent change | Standard Deviation 26.58 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [-35.04, -18.91]ANCOVA
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [-33.06, -18.12]ANCOVA
Secondary
Percent Change From Baseline in Peak Daily Pruritus NRS Score to Week 2
Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]).
Time frame: Baseline to Week 2
Population: Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Peak Daily Pruritus NRS Score to Week 2 | -4.2 percent change | Standard Deviation 22.77 |
| Dupilumab 300 mg q2w | Percent Change From Baseline in Peak Daily Pruritus NRS Score to Week 2 | -20.4 percent change | Standard Deviation 21.4 |
| Dupilumab 300 mg qw | Percent Change From Baseline in Peak Daily Pruritus NRS Score to Week 2 | -18.9 percent change | Standard Deviation 28.4 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [-21.08, -11.9]ANCOVA
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [-19.62, -10.5]ANCOVA
Secondary
Percent Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16
Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]).
Time frame: Baseline to Week 16
Population: Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16 | -26.8 percent change | Standard Deviation 28.38 |
| Dupilumab 300 mg q2w | Percent Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16 | -51.1 percent change | Standard Deviation 28.81 |
| Dupilumab 300 mg qw | Percent Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16 | -49.0 percent change | Standard Deviation 33.45 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [-32.26, -17.52]ANCOVA
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [-30.33, -15.33]ANCOVA
Secondary
Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 16
SCORAD is a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease).
Time frame: Baseline to Week 16
Population: Full analysis set (FAS) included all randomized participants. Here, number of participants analyzed = participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 16 | -28.9 percent change | Standard Deviation 24.25 |
| Dupilumab 300 mg q2w | Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 16 | -57.2 percent change | Standard Deviation 24.03 |
| Dupilumab 300 mg qw | Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 16 | -56.7 percent change | Standard Deviation 24.27 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [-35.79, -21.54]ANCOVA
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous outcome measure was statistically significant).p-value: <0.000195% CI: [-35.09, -20.87]ANCOVA