Dermatitis, Atopic, Dermatitis, Dermatitis Atopic, Disease, Eczematous Skin, Diseases Genetic, Genetic, Diseases Inborn, Skin, Eczema, Skin Diseases, Skin, Hypersensitivity, Immediate, Hypersensitivity, Immune System Diseases, Moderate-to-Severe Atopic Dermatitis
Conditions
Brief summary
The primary objective of the study was to demonstrate the efficacy of dupilumab as a monotherapy in participants ≥12 years to \<18 years of age with moderate-to-severe atopic dermatitis (AD). The secondary objective of the study was to assess the safety of dupilumab as a monotherapy in participants ≥12 years to \<18 years of age with moderate-to-severe AD.
Interventions
DRUGDupilumab
Subcutaneous injection among the different quadrants of the abdomen (avoiding navel and waist areas), upper thighs, and upper arms.
DRUGPlacebo
Subcutaneous injection among the different quadrants of the abdomen (avoiding navel and waist areas), upper thighs, and upper arms.
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male or female ≥12 to \<18 years of age at time of screening visit * Diagnosis of AD according to the American Academy of Dermatology consensus criteria at screening visit * IGA ≥3 at screening and baseline visit * EASI ≥16 at the screening and baseline visit * Baseline Pruritus NRS average score for maximum itch intensity ≥4 * ≥10% BSA of AD involvement at the screening and baseline visits * With documented recent history (within 6 months before the screening visit) of inadequate response to topical AD medication(s) or for whom topical treatments is medically inadvisable
Exclusion criteria
* Participation in a prior dupilumab clinical study * Treatment with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) within 2 weeks before the baseline visit * Having used immunosuppressive/immunomodulating drugs within 4 weeks before the baseline visit * Body weight \<30 kg at baseline * Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the baseline visit * Known or suspected immunodeficiency, known history of human immunodeficiency virus (HIV) infection or HIV seropositivity at the screening visit, established diagnosis of HBV infection or HBV seropositivity at screening, established diagnosis of HCV infection or HCV seropositivity at screening * History of malignancy before the baseline visit * Diagnosed active endoparasitic infections or at high risk of these infections * Patient is female who is pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study * Patient is female of childbearing potential and sexually active, who is unwilling to use adequate methods of contraception throughout the duration of the study and for 120 days after the last dose of study drug Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Investigator's Global Assessment (IGA) 0 or 1 (and Reduction From Baseline of ≥2 Points) at Week 16 | Baseline and Week 16 | IGA is an assessment scale used to determine severity of atopic dermatitis (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 was an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA 0 or 1 and a reduction from baseline of ≥2 points at Week 16 were reported. \[Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder. Participant considered non-responder after rescue treatment use. Efficacy analyses were based on the treatment allocated at randomization (as randomized).\] |
| Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Improvement From Baseline) at Week 16 | Baseline and Week 16 | The EASI score was used to measure the severity and extent of AD and measures 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. \[Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder. Participant considered nonresponder after rescue treatment use. Efficacy analyses were based on the treatment allocated at randomization (as randomized).\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16 | Baseline to Week 16 | Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours? \[For this endpoint, participants achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.\] |
| Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16 | Baseline to Week 16 | Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours? \[For this endpoint, participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.\] |
| Percentage of Participants With EASI-50 (≥50% Improvement From Baseline) at Week 16 | Baseline and 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 at Week 16. \[Values after first rescue treatment used were set to missing. Participants with missing value at Week 16 were considered as a non-responder\]. |
| Percentage of Participants With EASI-90 (≥90% Improvement From Baseline) at Week 16 | Baeline and 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 at Week 16. \[Values after first rescue treatment used were set to missing. Participants with missing value at week 16 were considered as a non-responder.\] |
| Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline | Baseline up to week 16 | Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours? \[For this endpoint, participants achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.\] |
| Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline | Baseline up to Week 16 | Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours? \[For this endpoint, subjects achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.\] |
| Change From Baseline in Percent Body Surface Area (BSA) at Week 16 | Baseline and 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. |
| Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16 | Baseline and Week 16 | The SCORAD index is a clinical tool for assessing the severity of atopic dermatitis. 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). |
| Percent Change From Baseline in EASI Score at Week 16 | Baseline and Week 16 | The Eczema Area and Severity Index (EASI) score was used to measure the severity and extent of AD and measures 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. \[Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 16 were considered as non-responders.\] |
| Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16 | Baseline and Week 16 | The POEM is a 7-item, validated questionnaire used in clinical practice and clinical trials to assess disease symptoms in children and adults with atopic eczema. The format is subject response to 7 items (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) based on symptom frequency during the past week (ie, 0 = 'no days', 1 = '1 to 2 days', 2 = '3 to 4 days', 3 = '5 to 6' days, and 4 = 'every day'). The total score is the sum of the 7 items which is ranged from 0 to 28; a high score is indicative of a poor quality of life (QOL). |
| Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 16 | Baseline and Week 16 | Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Particpants were asked the following question for maximum itch intensity: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours? For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3)/ 3. |
| Percent Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 4 | Baseline and Week 4 | Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question for maximum itch intensity: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours? For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3)/ 3. |
| Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) at Week 16 | Baseline and Week 16 | The HADS is 14-item questionnaire with two subscales: anxiety & depression. Each item is rated on a 4-point scale (0-3). A person could score between 0 & 21 for each subscale (anxiety & depression). A high score is indicative of a poor state. Scores of 11 or more on either subscale are considered a 'definite case' of psychological morbidity, while scores of 8 to 10 represents 'probable case' & 0 to 7 'not a case'. The total score was the sum of the 2 sub-scores; therefore, the full range of possible values for the reported data is 0-42. |
| Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline at Week 4 | Baseline and Week 4 | Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question for maximum itch intensity: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours? For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3)/ 3. |
| Percentage of Participants With Skin-infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Through Week 16 | Baseline through Week 16 | Any untoward medical occurrence in a subject 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 16)). 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 Serious TEAEs Through Week 16 | 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. |
| Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Total Score at Week 16 | Baseline and Week 16 | The CDLQI is a 10-item questionnaire used to measure how much a participant's skin problem had affected the participant's quality of life (QOL) over a recall period of the past week. The questionnaire consists of 10 items. For each item the scale is rated as follows: 0 = Not at all = Not relevant; 1 = Only a little; 2 = Quite a lot; 3 = Very much = Yes = Prevents school. The CDLQI total score is the sum of the score of each question with a maximum of 30 and a minimum of 0. The higher the score, the greater the impact is on the QOL. |
| Percent Change From Baseline in Weekly Average of Daily Peak Pruritus Numerical Rating Scale (NRS) Score at Week 16 | Baseline and Week 16 | Peak Pruritus NRS is an assessment tool used by subjects to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours? For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3) /3. \[Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.\] |
Countries
Canada, United States
Participant flow
Recruitment details
The study was conducted at 45 sites in the United States and Canada between 21 Mar 2017 and 05 Jun 2018. A total of 295 participants were screened, of which, 251 were eligible. The most common causes for screening failures were lack of adequate disease severity and lack of willingness to comply with study visits and procedures.
Pre-assignment details
Eligible participants were randomized (1:1:1) & stratified by baseline Investigator's Global Assessment (IGA) score (3 vs 4) & body weight (\<60 kg vs ≥60 kg) to 16 wks treatment with dupilumab every 2 wks (q2w) or q4w,or placebo q2w.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matching dupilumab once every 2 weeks (Q2W) (including doubling the amount of placebo on day 1 to match the loading dose). Participants in the \<60-kilogram (kg) weight stratum received, in a 1:1 ratio, either placebo matching 200 milligram (mg) or placebo matching 300 milligram (mg). In the ≥60 kg weight stratum, the participants randomized to the placebo group received placebo matching 300 mg dupilumab. | 85 |
| Dupilumab 300 mg Q4W Participants received once every 4 weeks (Q4W) subcutaneous (SC) injections of 300 milligrams (mg) dupilumab following a loading dose of 600 mg on day 1. To maintain blinding, all participants received an injection once every 2 weeks (Q2W) from day 1 to week 14. Participants received placebo 2 millilitre (mL) injection at the weeks dupilumab was not given. | 84 |
| Dupilumab 200 mg or 300 mg Q2W Participants with baseline weight \<60 kg received once every 2 weeks (Q2W) subcutaneous (SC) injections of 200 milligrams (mg) dupilumab following a loading dose of 400 mg on day 1. Participants with baseline weight ≥60 kg received Q2W SC injections of 300 mg dupilumab following a loading dose of 600 mg on day 1. | 82 |
| Total | 251 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Discont'd to enroll in OLE: not enrolled | 1 | 0 | 0 |
| Overall Study | Discontinued to enroll in OLE: enrolled | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 3 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 | 1 |
| Overall Study | Transitioned to OLE study | 76 | 76 | 73 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 3 |
Baseline characteristics
| Characteristic | Placebo | Dupilumab 300 mg Q4W | Dupilumab 200 mg or 300 mg Q2W | Total |
|---|---|---|---|---|
| Age, Continuous | 14.5 years STANDARD_DEVIATION 1.78 | 14.4 years STANDARD_DEVIATION 1.59 | 14.5 years STANDARD_DEVIATION 1.74 | 14.5 years STANDARD_DEVIATION 1.7 |
| Age, Customized ≥12 to <15 years of age | 41 Participants | 45 Participants | 43 Participants | 129 Participants |
| Age, Customized ≥15 to <18 years of age | 44 Participants | 39 Participants | 39 Participants | 122 Participants |
| Body Surface Area (BSA) of Atopic Dermatitis (AD) | 56.4 Percentage of BSA STANDARD_DEVIATION 24.13 | 56.9 Percentage of BSA STANDARD_DEVIATION 23.51 | 56.0 Percentage of BSA STANDARD_DEVIATION 21.4 | 56.5 Percentage of BSA STANDARD_DEVIATION 22.97 |
| Children's Dermatology Life Quality Index (CDLQI) Total Score | 13.1 Scores on a scale STANDARD_DEVIATION 6.72 | 14.8 Scores on a scale STANDARD_DEVIATION 7.38 | 13.0 Scores on a scale STANDARD_DEVIATION 6.21 | 13.6 Scores on a scale STANDARD_DEVIATION 6.82 |
| Duration of Atopic Dermatitis (AD) | 12.3 Years STANDARD_DEVIATION 3.44 | 11.9 Years STANDARD_DEVIATION 3.18 | 12.5 Years STANDARD_DEVIATION 2.97 | 12.2 Years STANDARD_DEVIATION 3.2 |
| Eczema Area and Severity Index (EASI) Score | 35.5 Scores on a scale STANDARD_DEVIATION 13.97 | 35.8 Scores on a scale STANDARD_DEVIATION 14.82 | 35.3 Scores on a scale STANDARD_DEVIATION 13.84 | 35.5 Scores on a scale STANDARD_DEVIATION 14.16 |
| Investigator's Global Assessment (IGA) Score IGA score = 3 (moderate) | 39 Participants | 38 Participants | 39 Participants | 116 Participants |
| Investigator's Global Assessment (IGA) Score IGA score = 4 (severe) | 46 Participants | 46 Participants | 43 Participants | 135 Participants |
| Patient Oriented Eczema Measure (POEM) | 21.1 Scores on a scale STANDARD_DEVIATION 5.38 | 21.1 Scores on a scale STANDARD_DEVIATION 5.47 | 21.0 Scores on a scale STANDARD_DEVIATION 5.01 | 21.0 Scores on a scale STANDARD_DEVIATION 5.27 |
| Peak Weekly Averaged Pruritus Numerical Rating Scale (NRS) Score | 7.7 Peak weekly average score STANDARD_DEVIATION 1.62 | 7.5 Peak weekly average score STANDARD_DEVIATION 1.84 | 7.5 Peak weekly average score STANDARD_DEVIATION 1.52 | 7.6 Peak weekly average score STANDARD_DEVIATION 1.66 |
| Race/Ethnicity, Customized Asian | 13 Participants | 13 Participants | 12 Participants | 38 Participants |
| Race/Ethnicity, Customized Black or African American | 15 Participants | 8 Participants | 7 Participants | 30 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 13 Participants | 20 Participants | 13 Participants | 46 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 72 Participants | 64 Participants | 69 Participants | 205 Participants |
| Race/Ethnicity, Customized Not Reported/ Missing | 3 Participants | 0 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Other | 6 Participants | 8 Participants | 7 Participants | 21 Participants |
| Race/Ethnicity, Customized White | 48 Participants | 55 Participants | 54 Participants | 157 Participants |
| Scoring Atopic Dermatitis (SCORAD) Score | 70.4 Scores on a scale STANDARD_DEVIATION 13.25 | 69.8 Scores on a scale STANDARD_DEVIATION 14.12 | 70.6 Scores on a scale STANDARD_DEVIATION 13.89 | 70.3 Scores on a scale STANDARD_DEVIATION 13.7 |
| Sex: Female, Male Female | 32 Participants | 32 Participants | 39 Participants | 103 Participants |
| Sex: Female, Male Male | 53 Participants | 52 Participants | 43 Participants | 148 Participants |
| Total Hospital Anxiety and Depression Scale (HADS) | 11.6 Scores on a scale STANDARD_DEVIATION 7.76 | 13.3 Scores on a scale STANDARD_DEVIATION 8.17 | 12.6 Scores on a scale STANDARD_DEVIATION 8.04 | 12.5 Scores on a scale STANDARD_DEVIATION 7.99 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 85 | 0 / 83 | 0 / 82 |
| other Total, other adverse events | 40 / 85 | 34 / 83 | 39 / 82 |
| serious Total, serious adverse events | 1 / 85 | 0 / 83 | 0 / 82 |
Outcome results
Primary
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Improvement From Baseline) at Week 16
The EASI score was used to measure the severity and extent of AD and measures 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. \[Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder. Participant considered nonresponder after rescue treatment use. Efficacy analyses were based on the treatment allocated at randomization (as randomized).\]
Time frame: Baseline and Week 16
Population: Analysis was performed on Full Analysis Set (FAS) population (all randomized participants).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Improvement From Baseline) at Week 16 | 8.2 Percentage of participants |
| Dupilumab 300 mg Q4W | Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Improvement From Baseline) at Week 16 | 38.1 Percentage of participants |
| Dupilumab 200 mg or 300 mg Q2W | Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Improvement From Baseline) at Week 16 | 41.5 Percentage of participants |
Comparison: A hierarchical testing procedure was used to control type I error. Analysis was performed using CMH test stratified by baseline disease severity (IGA=3 vs IGA=4) and baseline weight group (\<60 kg vs ≥60 kg).p-value: <0.000195% CI: [21.07, 45.39]Cochran-Mantel-Haenszel
Comparison: A hierarchical testing procedure was used to control type I error. Analysis was performed using CMH test stratified by baseline disease severity (IGA=3 vs IGA=4) and baseline weight group (\<60 kg vs ≥60 kg).p-value: <0.000195% CI: [17.94, 41.78]Cochran-Mantel-Haenszel
Primary
Percentage of Participants With Investigator's Global Assessment (IGA) 0 or 1 (and Reduction From Baseline of ≥2 Points) at Week 16
IGA is an assessment scale used to determine severity of atopic dermatitis (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 was an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA 0 or 1 and a reduction from baseline of ≥2 points at Week 16 were reported. \[Values after first rescue treatment used were set to missing. Participants with missing score at week 16 were considered as a non-responder. Participant considered non-responder after rescue treatment use. Efficacy analyses were based on the treatment allocated at randomization (as randomized).\]
Time frame: Baseline and Week 16
Population: Analysis was performed on Full Analysis Set (FAS) population (all randomized participants).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Investigator's Global Assessment (IGA) 0 or 1 (and Reduction From Baseline of ≥2 Points) at Week 16 | 2.4 Percentage of participants |
| Dupilumab 300 mg Q4W | Percentage of Participants With Investigator's Global Assessment (IGA) 0 or 1 (and Reduction From Baseline of ≥2 Points) at Week 16 | 17.9 Percentage of participants |
| Dupilumab 200 mg or 300 mg Q2W | Percentage of Participants With Investigator's Global Assessment (IGA) 0 or 1 (and Reduction From Baseline of ≥2 Points) at Week 16 | 24.4 Percentage of participants |
Comparison: A hierarchical testing procedure was used to control type I error. Analysis was performed using Cochran-Mantel-Haenszel (CMH) test stratified by baseline disease severity (IGA=3 vs IGA=4) and baseline weight group (less than \[\<\] 60 kilogram \[kg\] vs greater than or equal to \[≥\] 60 kg).p-value: <0.000195% CI: [12.2, 31.87]Cochran-Mantel-Haenszel
Comparison: A hierarchical testing procedure was used to control type I error. Analysis was performed using CMH test stratified by baseline disease severity (IGA=3 vs IGA=4) and baseline weight group (\<60 kg vs ≥60 kg).p-value: =0.000795% CI: [6.7, 24.31]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Total Score at Week 16
The CDLQI is a 10-item questionnaire used to measure how much a participant's skin problem had affected the participant's quality of life (QOL) over a recall period of the past week. The questionnaire consists of 10 items. For each item the scale is rated as follows: 0 = Not at all = Not relevant; 1 = Only a little; 2 = Quite a lot; 3 = Very much = Yes = Prevents school. The CDLQI total score is the sum of the score of each question with a maximum of 30 and a minimum of 0. The higher the score, the greater the impact is on the QOL.
Time frame: Baseline and Week 16
Population: Analysis was performed on FAS population (all randomized participants).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Total Score at Week 16 | -5.1 Scores on a scale | Standard Error 0.62 |
| Dupilumab 300 mg Q4W | Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Total Score at Week 16 | -8.8 Scores on a scale | Standard Error 0.53 |
| Dupilumab 200 mg or 300 mg Q2W | Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Total Score at Week 16 | -8.5 Scores on a scale | Standard Error 0.5 |
Secondary
Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16
The POEM is a 7-item, validated questionnaire used in clinical practice and clinical trials to assess disease symptoms in children and adults with atopic eczema. The format is subject response to 7 items (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) based on symptom frequency during the past week (ie, 0 = 'no days', 1 = '1 to 2 days', 2 = '3 to 4 days', 3 = '5 to 6' days, and 4 = 'every day'). The total score is the sum of the 7 items which is ranged from 0 to 28; a high score is indicative of a poor quality of life (QOL).
Time frame: Baseline and Week 16
Population: Analysis was performed on FAS population (all randomized participants).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16 | -3.8 Scores on a scale | Standard Error 0.96 |
| Dupilumab 300 mg Q4W | Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16 | -9.5 Scores on a scale | Standard Error 0.86 |
| Dupilumab 200 mg or 300 mg Q2W | Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16 | -10.1 Scores on a scale | Standard Error 0.76 |
Secondary
Change From Baseline in Percent Body Surface Area (BSA) at 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 and Week 16
Population: Analysis was performed on FAS population (all randomized participants).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Percent Body Surface Area (BSA) at Week 16 | -11.66 Percentage of body surface area | Standard Error 2.72 |
| Dupilumab 300 mg Q4W | Change From Baseline in Percent Body Surface Area (BSA) at Week 16 | -33.41 Percentage of body surface area | Standard Error 2.33 |
| Dupilumab 200 mg or 300 mg Q2W | Change From Baseline in Percent Body Surface Area (BSA) at Week 16 | -30.11 Percentage of body surface area | Standard Error 2.337 |
Secondary
Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) at Week 16
The HADS is 14-item questionnaire with two subscales: anxiety & depression. Each item is rated on a 4-point scale (0-3). A person could score between 0 & 21 for each subscale (anxiety & depression). A high score is indicative of a poor state. Scores of 11 or more on either subscale are considered a 'definite case' of psychological morbidity, while scores of 8 to 10 represents 'probable case' & 0 to 7 'not a case'. The total score was the sum of the 2 sub-scores; therefore, the full range of possible values for the reported data is 0-42.
Time frame: Baseline and Week 16
Population: Analysis was performed on FAS population (all randomized participants).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) at Week 16 | -2.5 Scores on a scale | Standard Error 0.8 |
| Dupilumab 300 mg Q4W | Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) at Week 16 | -5.2 Scores on a scale | Standard Error 0.73 |
| Dupilumab 200 mg or 300 mg Q2W | Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) at Week 16 | -3.8 Scores on a scale | Standard Error 0.68 |
Secondary
Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 16
Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Particpants were asked the following question for maximum itch intensity: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours? For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3)/ 3.
Time frame: Baseline and Week 16
Population: Analysis was performed on FAS population (all randomized participants).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 16 | -1.54 Scores on a scale | Standard Error 0.303 |
| Dupilumab 300 mg Q4W | Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 16 | -3.44 Scores on a scale | Standard Error 0.26 |
| Dupilumab 200 mg or 300 mg Q2W | Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 16 | -3.70 Scores on a scale | Standard Error 0.25 |
Secondary
Percentage of Participants With 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 at Week 16. \[Values after first rescue treatment used were set to missing. Participants with missing value at Week 16 were considered as a non-responder\].
Time frame: Baseline and Week 16
Population: Analysis was performed on FAS population (all randomized participants).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With EASI-50 (≥50% Improvement From Baseline) at Week 16 | 12.9 Percentage of participants |
| Dupilumab 300 mg Q4W | Percentage of Participants With EASI-50 (≥50% Improvement From Baseline) at Week 16 | 54.8 Percentage of participants |
| Dupilumab 200 mg or 300 mg Q2W | Percentage of Participants With EASI-50 (≥50% Improvement From Baseline) at Week 16 | 61.0 Percentage of participants |
Secondary
Percentage of Participants With 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 at Week 16. \[Values after first rescue treatment used were set to missing. Participants with missing value at week 16 were considered as a non-responder.\]
Time frame: Baeline and Week 16
Population: Analysis was performed on FAS population (all randomized participants).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With EASI-90 (≥90% Improvement From Baseline) at Week 16 | 2.4 Percentage of participants |
| Dupilumab 300 mg Q4W | Percentage of Participants With EASI-90 (≥90% Improvement From Baseline) at Week 16 | 19.0 Percentage of participants |
| Dupilumab 200 mg or 300 mg Q2W | Percentage of Participants With EASI-90 (≥90% Improvement From Baseline) at Week 16 | 23.2 Percentage of participants |
Secondary
Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16
Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours? \[For this endpoint, participants achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.\]
Time frame: Baseline to Week 16
Population: Analysis was performed on FAS population (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 Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16 | 9.4 Percentage of participants |
| Dupilumab 300 mg Q4W | Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16 | 38.6 Percentage of participants |
| Dupilumab 200 mg or 300 mg Q2W | Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16 | 48.8 Percentage of participants |
Comparison: A hierarchical testing procedure was used to control type I error. Difference is Dupilumab minus Placebo. C.I. = Confidence interval calculated using normal approximation. P-values were derived by CMH test stratified by baseline disease severity \[IGA=3 vs IGA=4\] and baseline weight group \[\<60 kg vs ≥60 kg\].p-value: <0.000195% CI: [26.9, 51.84]Cochran-Mantel-Haenszel
Comparison: A hierarchical testing procedure was used to control type I error. Difference is Dupilumab minus Placebo. C.I. = Confidence interval calculated using normal approximation. P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by baseline disease severity \[IGA=3 vs IGA=4\] and baseline weight group \[\<60 kg vs ≥60 kg\].p-value: <0.000195% CI: [16.97, 41.32]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline at Week 4
Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question for maximum itch intensity: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours? For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3)/ 3.
Time frame: Baseline and Week 4
Population: Analysis was performed on FAS population (all randomized participants).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline at Week 4 | 4.8 Percentage of participants |
| Dupilumab 300 mg Q4W | Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline at Week 4 | 20.5 Percentage of participants |
| Dupilumab 200 mg or 300 mg Q2W | Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline at Week 4 | 22.0 Percentage of participants |
Secondary
Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16
Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours? \[For this endpoint, participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.\]
Time frame: Baseline to Week 16
Population: Analysis was performed on FAS population (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 Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16 | 4.8 Percentage of participants |
| Dupilumab 300 mg Q4W | Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16 | 26.5 Percentage of participants |
| Dupilumab 200 mg or 300 mg Q2W | Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline to Week 16 | 36.6 Percentage of participants |
Comparison: A hierarchical testing procedure was used to control type I error. Difference is Dupilumab minus Placebo. C.I. = Confidence interval calculated using normal approximation. P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by baseline disease severity \[IGA=3 vs IGA=4\] and baseline weight group \[\<60 kg vs ≥60 kg\].p-value: <0.000195% CI: [20.45, 43.2]Cochran-Mantel-Haenszel
Comparison: A hierarchical testing procedure was used to control type I error. Difference is Dupilumab minus Placebo. C.I. = Confidence interval calculated using normal approximation. P-values were derived by Cochran-Mantel-Haenszel (CMH) test stratified by baseline disease severity \[IGA=3 vs IGA=4\] and baseline weight group \[\<60 kg vs ≥60 kg\].p-value: =0.000195% CI: [11.21, 32.28]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Serious TEAEs 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 through Week 16
Population: Analysis was performed on FAS population (all randomized participants). Here, number of participants analyzed = participants with available data for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Serious TEAEs Through Week 16 | 1.2 Percentage of participants |
| Dupilumab 300 mg Q4W | Percentage of Participants With Serious TEAEs Through Week 16 | 0 Percentage of participants |
| Dupilumab 200 mg or 300 mg Q2W | Percentage of Participants With Serious TEAEs Through Week 16 | 0 Percentage of participants |
Secondary
Percentage of Participants With Skin-infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Through Week 16
Any untoward medical occurrence in a subject 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 16)). 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 through Week 16
Population: Analysis was performed on FAS population (all randomized participants). Here, number of participants analyzed = participants with available data for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Skin-infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Through Week 16 | 18.8 Percentage of participants |
| Dupilumab 300 mg Q4W | Percentage of Participants With Skin-infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Through Week 16 | 9.6 Percentage of participants |
| Dupilumab 200 mg or 300 mg Q2W | Percentage of Participants With Skin-infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Through Week 16 | 9.8 Percentage of participants |
Secondary
Percent Change From Baseline in EASI Score at Week 16
The Eczema Area and Severity Index (EASI) score was used to measure the severity and extent of AD and measures 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. \[Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 16 were considered as non-responders.\]
Time frame: Baseline and Week 16
Population: Analysis was performed on FAS population (all randomized participants).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in EASI Score at Week 16 | -23.6 Percent change | Standard Error 5.49 |
| Dupilumab 300 mg Q4W | Percent Change From Baseline in EASI Score at Week 16 | -64.8 Percent change | Standard Error 4.51 |
| Dupilumab 200 mg or 300 mg Q2W | Percent Change From Baseline in EASI Score at Week 16 | -65.9 Percent change | Standard Error 3.99 |
Comparison: A hierarchical testing procedure was used to control type I error. The confidence interval (CI) with p-value is based on treatment difference (Dupilumab group vs. Placebo) of the LS mean percent change using analysis of covariance (ANCOVA) model with baseline measurement as covariate and the treatment, randomization strata (baseline disease severity \[IGA=3 vs IGA=4\] and baseline weight group \[\<60 kg vs ≥60 kg\]) as fixed factors.p-value: <0.000195% CI: [-55.6, -29.04]ANCOVA
Comparison: A hierarchical testing procedure was used to control type I error. The confidence interval (CI) with p-value is based on treatment difference (Dupilumab group vs. Placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata (baseline disease severity \[IGA=3 vs IGA=4\] and baseline weight group \[\<60 kg vs ≥60 kg\]) as fixed factors.p-value: <0.000195% CI: [-54.44, -28.02]ANCOVA
Secondary
Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16
The SCORAD index is a clinical tool for assessing the severity of atopic dermatitis. 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 and Week 16
Population: Analysis was performed on FAS population (all randomized participants).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16 | -17.6 Percent change | Standard Error 3.76 |
| Dupilumab 300 mg Q4W | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16 | -47.5 Percent change | Standard Error 3.21 |
| Dupilumab 200 mg or 300 mg Q2W | Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 16 | -51.6 Percent change | Standard Error 3.23 |
Secondary
Percent Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 4
Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question for maximum itch intensity: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours? For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3)/ 3.
Time frame: Baseline and Week 4
Population: Analysis was performed on FAS population (all randomized participants).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 4 | -12.5 Percent change | Standard Error 3.06 |
| Dupilumab 300 mg Q4W | Percent Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 4 | -33.1 Percent change | Standard Error 3.05 |
| Dupilumab 200 mg or 300 mg Q2W | Percent Change From Baseline in Weekly Average of Daily Peak Pruritus NRS at Week 4 | -34.7 Percent change | Standard Error 2.99 |
Secondary
Percent Change From Baseline in Weekly Average of Daily Peak Pruritus Numerical Rating Scale (NRS) Score at Week 16
Peak Pruritus NRS is an assessment tool used by subjects to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours? For post-baseline NRS, the mean weekly NRS was calculated as the prorated average of the reported daily NRS within the week. For example, if there were 3 scores in a week, the prorated average = (score1 + score2 + score3) /3. \[Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.\]
Time frame: Baseline and Week 16
Population: Analysis was performed on FAS population (all randomized participants).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Weekly Average of Daily Peak Pruritus Numerical Rating Scale (NRS) Score at Week 16 | -19.0 Percent change | Standard Error 4.09 |
| Dupilumab 300 mg Q4W | Percent Change From Baseline in Weekly Average of Daily Peak Pruritus Numerical Rating Scale (NRS) Score at Week 16 | -45.5 Percent change | Standard Error 3.54 |
| Dupilumab 200 mg or 300 mg Q2W | Percent Change From Baseline in Weekly Average of Daily Peak Pruritus Numerical Rating Scale (NRS) Score at Week 16 | -47.9 Percent change | Standard Error 3.43 |
Comparison: A hierarchical testing procedure was used to control type I error. The confidence interval (CI) with p-value is based on treatment difference (Dupilumab group vs. Placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata (baseline disease severity \[IGA=3 vs IGA=4\] and baseline weight group \[\<60 kg vs ≥60 kg\]) as fixed factors.p-value: <0.000195% CI: [-39.54, -18.38]ANCOVA
Comparison: A hierarchical testing procedure was used to control type I error. The confidence interval (CI) with p-value is based on treatment difference (Dupilumab group vs. Placebo) of the LS mean percent change using ANCOVA model with baseline measurement as covariate and the treatment, randomization strata (baseline disease severity \[IGA=3 vs IGA=4\] and baseline weight group \[\<60 kg vs ≥60 kg\]) as fixed factors.p-value: <0.000195% CI: [-37.45, 15.63]ANCOVA
Secondary
Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline
Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours? \[For this endpoint, participants achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.\]
Time frame: Baseline up to week 16
Population: Analysis was performed on FAS population (all randomized participants). Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline | 11.4 Percentage of participants | Standard Deviation 5.63 |
| Dupilumab 300 mg Q4W | Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline | 8.4 Percentage of participants | Standard Deviation 5.92 |
| Dupilumab 200 mg or 300 mg Q2W | Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥3 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline | 7.7 Percentage of participants | Standard Deviation 5.57 |
Secondary
Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline
Peak Pruritus NRS is an assessment tool used by participants to report intensity of pruritus (itch) during a 24-hour recall period. Participants were asked the following question: For maximum itch intensity: On a scale of 0 to 10, with 0 being 'no itch' and 10 being the 'worst itch imaginable,' how would you rate your itch at the worst moment during the previous 24 hours? \[For this endpoint, subjects achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported. Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 16 were counted as non-responders.\]
Time frame: Baseline up to Week 16
Population: Analysis was performed on FAS population (all randomized participants). Here, number of participants analyzed = participants with baseline peak pruritus NRS ≥4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline | 12.8 Percentage of participants | Standard Deviation 4.9 |
| Dupilumab 300 mg Q4W | Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline | 9.9 Percentage of participants | Standard Deviation 5.87 |
| Dupilumab 200 mg or 300 mg Q2W | Time to Onset of Effect on Pruritus as Measured by Percentage of Participants With Improvement (Reduction ≥4 Points) of Weekly Average of Daily Peak Pruritus NRS From Baseline | 10.6 Percentage of participants | Standard Deviation 5.5 |