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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-003384-38 | EudraCT Number |
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| Name | Class |
|---|---|
| Sanofi | INDUSTRY |
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The primary objective of the study was to assess the ability of different Dupilumab dose regimens, administered as monotherapy, to maintain the treatment response achieved after 16 weeks of initial treatment with Dupilumab monotherapy compared to placebo.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Subcutaneous injection of Placebo (for Dupilumab) was administered once weekly (QW) from Week 1 (Day 1) to Week 36. |
|
| Dupilumab 300 mg Q8W | Experimental | Subcutaneous injection of Dupilumab 300 milligram (mg) alternatively with placebo (matched to Dupilumab) was administered once every eight week (Q8W) from Week 1 to Week 36. |
|
| Dupilumab 300 mg Q4W | Experimental | Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) was administered once every four week (Q4W) from Week 1 to Week 36. |
|
| Dupilumab 300 mg Q2W/QW | Experimental | Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) was administered once every week (QW) or twice a week (Q2W) from Week 1 to Week 36. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dupilumab | Drug | Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) was administered. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Difference Between Current Study Baseline and Week 36 in Percent Change in EASI From Parent Study Baseline (NCT02277743 and NCT02277769) | 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. Difference of percent change in EASI between current study baseline and week 36 in from parent study baseline (NCT02277743 and NCT02277769) was reported. Values after first rescue treatment used were set to missing before multiple imputation (MI). | Baseline (Parent Study), Baseline (Current Study) and Week 36 (Current study) |
| Percentage of Participants With Eczema Area and Severity Index >= 75% [EASI-75] at Baseline of Current Study Maintaining EASI-75 at Week 36 | 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 at Week 36. Values after first rescue treatment used were set to missing. Patients with missing value at week 36 were considered as a non-responder. | Week 36 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Maintaining Investigator Global Assessment (IGA) Response Within 1 Point of Baseline at Week 36 | 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 at baseline and maintaining within 1 point of baseline were reported as responders. Values after first rescue treatment used were set to missing. Participants with missing value at a visit were considered as a non-responder. |
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Key Inclusion Criteria:
Must have completed the treatment phase in 1 of the two 16-week initial treatment studies (R668-AD-1334 or R668-AD-1416).
Must have achieved at least 1 of the following 2 treatment success criteria:
Investigator Global Assessment (IGA) = 0 or 1 (clear or almost clear) at week 16 OR Eczema Area and Severity Index >= 75% (EASI-75) (at least 75% reduction in EASI score from baseline to week 16)
Must be willing and able to comply with clinic visits and study-related procedures
Must provide signed informed consent
Must be able to understand and complete study-related questionnaires
Key Exclusion Criteria:
(*For females, menopause is defined as at least 12 consecutive months without menses; if in question, a follicle stimulating hormone level of >= 25 milli units per milliliter (mU/mL) must be documented. Hysterectomy, bilateral oophorectomy, or bilateral tubal ligation must be documented, as applicable; if documented, women with these conditions are not required to use additional contraception).
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trial Management | Regeneron Pharmaceuticals | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39969783 | Derived | Stander S, Yosipovitch G, Simpson EL, Kim BS, Kabashima K, Thaci D, Metz M, Chen Z, Hagen S, Bastian M. Onset and Long-Term Maintenance of Optimal Itch Response in Adult Patients with Moderate-to-Severe Atopic Dermatitis Treated with Dupilumab: Post Hoc Analysis from Two Phase 3 Trials. Adv Ther. 2025 Apr;42(4):1800-1810. doi: 10.1007/s12325-025-03124-8. Epub 2025 Feb 19. | |
| 39588375 |
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Out of the 475 participants, 422 were randomized and 420 received either placebo or Dupilumab. Participants were randomized in 2:1:1:1 ratio to receive Dupilumab 300 milligram (mg) once weekly/twice weekly (QW/Q2W), Dupilumab 300 mg four times a week (Q4W), Dupilumab 300 mg eight times a week (Q8W) and Placebo.
The study was conducted in 15 countries between 25 March 2015 and 18 October 2016. A total of 422 participants were randomized in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo QW | Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36. |
| FG001 | Dupilumab 300 mg Q8W | Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36. |
| FG002 | Dupilumab 300 mg Q4W | Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36. |
| FG003 | Dupilumab 300 mg Q2W/QW | Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The full analysis set (FAS) included all randomized participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo QW | Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36. |
| BG001 | Dupilumab 300 mg Q8W | Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Difference Between Current Study Baseline and Week 36 in Percent Change in EASI From Parent Study Baseline (NCT02277743 and NCT02277769) | 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. Difference of percent change in EASI between current study baseline and week 36 in from parent study baseline (NCT02277743 and NCT02277769) was reported. Values after first rescue treatment used were set to missing before multiple imputation (MI). | The full analysis set (FAS) includes all randomized participants. | Posted | Least Squares Mean | Standard Error | percent change | Baseline (Parent Study), Baseline (Current Study) and Week 36 (Current study) |
|
All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 36) regardless of seriousness or relationship to investigational product.
Reported AEs are treatment-emergent adverse events that developed/worsened during the 'on-treatment period' (time from the first dose of study drug up to the end of study [Week 36]). The safety analysis set (SAF) included all randomized participants who received any amount of study drug. Note: One participant was randomized to Dupilumab Q2W/QW, but treated per Dupilumab Q4W arm and included in the SAF
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo QW | Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | meddra (18.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site reaction | General disorders | meddra (18.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Management | Regeneron Pharmaceuticals, Inc. | clinicaltrials@regeneron.com |
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| ID | Term |
|---|---|
| D003876 | Dermatitis, Atopic |
| D004485 | Eczema |
| ID | Term |
|---|---|
| D012873 | Skin Diseases, Genetic |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003872 | Dermatitis |
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| ID | Term |
|---|---|
| C582203 | dupilumab |
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|
| Placebo | Drug | Subcutaneous injection of Placebo (for Dupilumab) was administered once weekly (QW). |
|
| Baseline, Week 36 |
| Percentage of Participants Maintaining Investigator Global Assessment (IGA) Response at 0 or 1 Point at Week 36 | 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 at week 36 were reported as responders. Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 36 were considered as non-responders. | Week 36 |
| Percentage of Participants With Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score Increased by 3 or More Points From Baseline to Week 35 | 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]). Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 35 were considered as non-responders. | Baseline up to Week 35 |
| Time to First Event of Investigator's Global Assessment (IGA) >= 2 for Participants With IGA 0 or 1 at Baseline | 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). | Baseline up to Week 36 |
| Percentage of Participants With Increased Investigator's Global Assessment (IGA) Score 3 or 4 at Week 36 | 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). Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 36 were considered as responders (i.e. having a increase 3 or 4 of IGA value). | Week 36 |
| Percentage of Participants With Eczema Area and Severity Index-50 (EASI-50) (>= 50% Reduction in EASI Score) at Week 36 | 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 36. Values after first rescue treatment were set to missing and participants with missing EASI-50 scores at Week 36 were considered as non-responders. | Week 36 |
| Absolute Change From Baseline in Eczema Area and Severity Index (EASI) at Week 36 | 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. Values after first rescue treatment were set to missing and participants with missing Values at Week 36 were imputed by using multiple imputation method. | Baseline, Week 36 |
| Absolute Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 36 | 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). Values after first rescue treatment used were set to missing (censoring) before MI. | Baseline, Week 36 |
| Absolute Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score at Week 35 | 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]). Values after first rescue treatment used were set to missing before MI. | Baseline, Week 35 |
| Absolute Change From Baseline in Body Surface Area (BSA) Through Week 36 | 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. Values after first rescue treatment used were set to missing (censoring) before MI. | Baseline through Week 36 |
| Absolute Change From Baseline Through in Patient Oriented Eczema Measure (POEM) Through Week 36 | 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]). Values after first rescue treatment used were set to missing (censoring) before MI. | Baseline through Week 36 |
| Absolute Change From Baseline in Dermatology Life Quality Index (DLQI) Through Week 36 | 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. Values after first rescue treatment used were set to missing before MI. | Baseline through Week 36 |
| Absolute Change From Baseline in Hospital Anxiety Depression Scale (HADS) Through Week 36 | 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. Values after first rescue treatment used were set to missing before MI. | Baseline through Week 36 |
| Difference Between Current Study Baseline and Week 36 in Percent Change in SCORAD From Parent Study Baseline | 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). Values after first rescue treatment used were set to missing before MI. | Baseline (Parent Study), Baseline (Current Study) and Week 36 (Current study) |
| Difference Between Current Study Baseline and Week 35 in Percent Change in Peak Weekly Pruritus NRS From Parent Study Baseline | 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]). Values after first rescue treatment used were set to missing before MI. | Baseline (Parent Study), Baseline (Current Study) and Week 35 (Current study) |
| Annualized Event Rate of Skin Infection Treatment- Emergent Adverse Events (TEAEs) | 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 36]). 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. | Baseline through Week 36 |
| Annualized Event Rate of Flares | Rate of Flares defined as worsening of disease requiring initiation or escalation of rescue treatment. | Baseline through week 36 |
| Percentage of Well-Controlled Weeks During the On-treatment Period | Well-controlled weeks are those in which participants during their weekly IVRS call completion has their eczema been well-controlled over the last week during which no rescue treatments were administered. Percentage of well-controlled weeks during the on-treatment period were reported. | Baseline through Week 36 |
| Derived |
| Kamal MA, Kosloski MP, Lai CH, Partridge MA, Rajadhyaksha M, Kanamaluru V, Bansal A, Shabbir A, Shumel B, Ardeleanu M, Richards SM, Yan H, Xu CR, Rodriguez-Marco A, Xiao J, Khokhar FA, Gherardi G, Babilonia E, Maloney J, Mortensen E, Akinlade B, Braunstein N, Stahl N, Torri A, Davis JD, DiCioccio AT. Immunogenicity of dupilumab in adult and pediatric patients with atopic dermatitis. Front Immunol. 2024 Nov 11;15:1466372. doi: 10.3389/fimmu.2024.1466372. eCollection 2024. |
| 31876900 | Derived | Worm M, Simpson EL, Thaci D, Bissonnette R, Lacour JP, Beissert S, Kawashima M, Ferrandiz C, Smith CH, Beck LA, Chan KC, Chen Z, Akinlade B, Hultsch T, Staudinger H, Gadkari A, Eckert L, Davis JD, Rajadhyaksha M, Graham NMH, Pirozzi G, Stahl N, Yancopoulos GD, Ardeleanu M. Efficacy and Safety of Multiple Dupilumab Dose Regimens After Initial Successful Treatment in Patients With Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. 2020 Feb 1;156(2):131-143. doi: 10.1001/jamadermatol.2019.3617. |
| Lack of Efficacy |
|
| Protocol Violation |
|
| Lost to Follow-up |
|
| Pregnancy |
|
| Consent withdrawn with no reason given |
|
| Consent withdrawn with personal reason |
|
| Sponsor decision |
|
| Other than specified above |
|
| BG002 | Dupilumab 300 mg Q4W | Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36. |
| BG003 | Dupilumab 300 mg Q2W/QW | Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Eczema Area and Severity Index (EASI) Score | The EASI score was used to measure the severity and extent of atopic dermatitis (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 range from 0 (minimum) to 72 (maximum) points,with the higher scores reflecting the worse severity of AD. | Mean | Standard Deviation | units on a scale |
|
| Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) | Pruritus NRS scale is an assessment tool that is used to report the intensity of 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]). | Mean | Standard Deviation | units on a scale |
|
| Body Surface Area (BSA) Involvement with AD | Body surface area 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. | Mean | Standard Deviation | percentage of body surface area |
|
| SCORing Atopic Dermatitis (SCORAD) Score | SCORAD was 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.) were assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). | Mean | Standard Deviation | units on a scale |
|
| Patient Oriented Eczema Measure (POEM) | The POEM was a 7-item questionnaire that assessed 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]). | Mean | Standard Deviation | units on a scale |
|
| Dermatology Life Quality Index (DLQI) Score | 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 indicative of a poor QOL. | Mean | Standard Deviation | units on a scale |
|
| Total Hospital Anxiety Depression Scale (HADS) | The HADS is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 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. | Mean | Standard Deviation | units on a scale |
|
Subcutaneous injection of Placebo (for Dupilumab) was administered weekly (QW) from Week 1 (Day 1) to Week 36. |
| OG001 | Dupilumab 300 mg Q8W | Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36. |
| OG002 | Dupilumab 300 mg Q4W | Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36. |
| OG003 | Dupilumab 300 mg Q2W/QW | Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36. |
|
|
|
| Primary | Percentage of Participants With Eczema Area and Severity Index >= 75% [EASI-75] at Baseline of Current Study Maintaining EASI-75 at Week 36 | 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 at Week 36. Values after first rescue treatment used were set to missing. Patients with missing value at week 36 were considered as a non-responder. | FAS population was used. Here, number of participants analyzed = participants with EASI-75 at baseline. | Posted | Number | percentage of participants | Week 36 |
|
|
|
|
| Secondary | Percentage of Participants Maintaining Investigator Global Assessment (IGA) Response Within 1 Point of Baseline at Week 36 | 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 at baseline and maintaining within 1 point of baseline were reported as responders. Values after first rescue treatment used were set to missing. Participants with missing value at a visit were considered as a non-responder. | FAS population was used. Here, number of participants analyzed = participants with IGA 0 or 1 at Baseline from Interactive voice response system (IVRS). | Posted | Number | percentage of participants | Baseline, Week 36 |
|
|
|
|
| Secondary | Percentage of Participants Maintaining Investigator Global Assessment (IGA) Response at 0 or 1 Point at Week 36 | 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 at week 36 were reported as responders. Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 36 were considered as non-responders. | FAS population was used. Here, number of participants analyzed = participants with IGA 0 or 1 at Baseline from IVRS. | Posted | Number | percentage of participants | Week 36 |
|
|
|
|
| Secondary | Percentage of Participants With Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score Increased by 3 or More Points From Baseline to Week 35 | 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]). Values after first rescue treatment were set to missing and participants with missing peak NRS at Week 35 were considered as non-responders. | FAS population was used. Here, number of participants analyzed = participants with NRS <= 7 at Baseline. | Posted | Number | percentage of participants | Baseline up to Week 35 |
|
|
|
|
| Secondary | Time to First Event of Investigator's Global Assessment (IGA) >= 2 for Participants With IGA 0 or 1 at Baseline | 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). | FAS population was used. Here, number of participants analyzed = participants with IGA 0 or 1 at Baseline from IVRS. | Posted | Median | 95% Confidence Interval | Days | Baseline up to Week 36 |
|
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| Secondary | Percentage of Participants With Increased Investigator's Global Assessment (IGA) Score 3 or 4 at Week 36 | 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). Values after first rescue treatment were set to missing and participants with missing IGA scores at Week 36 were considered as responders (i.e. having a increase 3 or 4 of IGA value). | FAS population was used. Here, number of participants analyzed = participants with IGA 0 or 1 at Baseline from IVRS. | Posted | Number | percentage of participants | Week 36 |
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| Secondary | Percentage of Participants With Eczema Area and Severity Index-50 (EASI-50) (>= 50% Reduction in EASI Score) at Week 36 | 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 36. Values after first rescue treatment were set to missing and participants with missing EASI-50 scores at Week 36 were considered as non-responders. | FAS population was used. | Posted | Number | percentage of participants | Week 36 |
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| Secondary | Absolute Change From Baseline in Eczema Area and Severity Index (EASI) at Week 36 | 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. Values after first rescue treatment were set to missing and participants with missing Values at Week 36 were imputed by using multiple imputation method. | FAS population was used. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 36 |
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| Secondary | Absolute Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score at Week 36 | 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). Values after first rescue treatment used were set to missing (censoring) before MI. | FAS population was used. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 36 |
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| Secondary | Absolute Change From Baseline in Peak Daily Pruritus Numerical Rating Scale (NRS) Score at Week 35 | 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]). Values after first rescue treatment used were set to missing before MI. | FAS population was used. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline, Week 35 |
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| Secondary | Absolute Change From Baseline in Body Surface Area (BSA) Through Week 36 | 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. Values after first rescue treatment used were set to missing (censoring) before MI. | FAS population was used. | Posted | Least Squares Mean | Standard Error | meter square | Baseline through Week 36 |
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| Secondary | Absolute Change From Baseline Through in Patient Oriented Eczema Measure (POEM) Through Week 36 | 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]). Values after first rescue treatment used were set to missing (censoring) before MI. | FAS population was used. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline through Week 36 |
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| Secondary | Absolute Change From Baseline in Dermatology Life Quality Index (DLQI) Through Week 36 | 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. Values after first rescue treatment used were set to missing before MI. | FAS population was used. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline through Week 36 |
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| Secondary | Absolute Change From Baseline in Hospital Anxiety Depression Scale (HADS) Through Week 36 | 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. Values after first rescue treatment used were set to missing before MI. | FAS population was used. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline through Week 36 |
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| Secondary | Difference Between Current Study Baseline and Week 36 in Percent Change in SCORAD From Parent Study Baseline | 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). Values after first rescue treatment used were set to missing before MI. | FAS population was used. | Posted | Least Squares Mean | Standard Error | Percent change | Baseline (Parent Study), Baseline (Current Study) and Week 36 (Current study) |
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| Secondary | Difference Between Current Study Baseline and Week 35 in Percent Change in Peak Weekly Pruritus NRS From Parent Study Baseline | 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]). Values after first rescue treatment used were set to missing before MI. | FAS population was used. | Posted | Least Squares Mean | Standard Error | percent change | Baseline (Parent Study), Baseline (Current Study) and Week 35 (Current study) |
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| Secondary | Annualized Event Rate of Skin Infection Treatment- Emergent Adverse Events (TEAEs) | 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 36]). 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. | FAS population was used. | Posted | Median | 95% Confidence Interval | events per year | Baseline through Week 36 |
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| Secondary | Annualized Event Rate of Flares | Rate of Flares defined as worsening of disease requiring initiation or escalation of rescue treatment. | FAS population was used. | Posted | Median | 95% Confidence Interval | events per year | Baseline through week 36 |
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| Secondary | Percentage of Well-Controlled Weeks During the On-treatment Period | Well-controlled weeks are those in which participants during their weekly IVRS call completion has their eczema been well-controlled over the last week during which no rescue treatments were administered. Percentage of well-controlled weeks during the on-treatment period were reported. | The safety analysis set (SAF) included all randomized participants who received any amount of study drug. Here, number of participants analyzed = participants with available data for this endpoint. One participant was randomized to Dupilumab Q2W/QW, but treated per Dupilumab Q4W arm and included in SAF. | Posted | Mean | Standard Deviation | percentage of weeks | Baseline through Week 36 |
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| 0 |
| 82 |
| 1 |
| 82 |
| 55 |
| 82 |
| EG001 | Dupilumab 300 mg Q8W | Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every eight week (Q8W) from Week 1 to Week 36. | 0 | 84 | 3 | 84 | 43 | 84 |
| EG002 | Dupilumab 300 mg Q4W | Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every four week (Q4W) from Week 1 to Week 36. | 1 | 87 | 4 | 87 | 47 | 87 |
| EG003 | Dupilumab 300 mg Q2W/QW | Subcutaneous injection of Dupilumab 300 mg alternatively with placebo (matched to Dupilumab) once every week (QW) or twice a week (Q2W) from Week 1 to Week 36. | 0 | 167 | 6 | 167 | 72 | 167 |
| Tachycardia induced cardiomyopathy | Cardiac disorders | meddra (18.0) | Systematic Assessment |
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| Anaphylactic reaction | Immune system disorders | meddra (18.0) | Systematic Assessment |
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| Gun shot wound | Injury, poisoning and procedural complications | meddra (18.0) | Systematic Assessment |
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| Muscle injury | Injury, poisoning and procedural complications | meddra (18.0) | Systematic Assessment |
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| Open fracture | Injury, poisoning and procedural complications | meddra (18.0) | Systematic Assessment |
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| Road traffic accident | Injury, poisoning and procedural complications | meddra (18.0) | Systematic Assessment |
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| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | meddra (18.0) | Systematic Assessment |
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| Glioblastoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | meddra (18.0) | Systematic Assessment |
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| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | meddra (18.0) | Systematic Assessment |
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| Biochemical pregnancy | Pregnancy, puerperium and perinatal conditions | meddra (18.0) | Systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | meddra (18.0) | Systematic Assessment |
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| Dermatitis atopic | Skin and subcutaneous tissue disorders | meddra (18.0) | Systematic Assessment |
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| Abortion induced | Surgical and medical procedures | meddra (18.0) | Systematic Assessment |
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| Deep vein thrombosis | Vascular disorders | meddra (18.0) | Systematic Assessment |
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| Hypertension | Vascular disorders | meddra (18.0) | Systematic Assessment |
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| Ligament Rupture | Injury, poisoning and procedural complications | MedDRA (18.0) | Systematic Assessment |
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| Wound Dehiscence | Injury, poisoning and procedural complications | MedDRA (18.0) | Systematic Assessment |
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| Bronchitis | Infections and infestations | meddra (18.0) | Systematic Assessment |
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| Influenza | Infections and infestations | meddra (18.0) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | meddra (18.0) | Systematic Assessment |
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| Oral herpes | Infections and infestations | meddra (18.0) | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | meddra (18.0) | Systematic Assessment |
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| Headache | Nervous system disorders | meddra (18.0) | Systematic Assessment |
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| Dermatitis atopic | Skin and subcutaneous tissue disorders | meddra (18.0) | Systematic Assessment |
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The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D017443 | Skin Diseases, Eczematous |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region, baseline disease severity and Dupilumab regimen received in parent studies. | Cochran-Mantel-Haenszel | = 0.0004 | Threshold for significance at 0.05 level. | Percentage difference | 28.0 | 2-Sided | 95 | 13.32 | 42.58 | Superiority |
| Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region, baseline disease severity and Dupilumab regimen received in parent studies. | Cochran-Mantel-Haenszel | <0.0001 | Threshold for significance at 0.05 level. | Percentage difference | 41.2 | 2-Sided | 95 | 28.93 | 53.52 | Superiority |
| Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region, baseline disease severity and Dupilumab regimen received in parent studies. | Cochran-Mantel-Haenszel | = 0.0003 | Threshold for significance at 0.05 level. | Percentage difference | 33.5 | 2-Sided | 95 | 17.38 | 49.72 | Superiority |
| Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region, baseline disease severity and Dupilumab regimen received in parent studies. | Cochran-Mantel-Haenszel | <0.0001 | Threshold for significance at 0.05 level. | Percentage difference | 42.1 | 2-Sided | 95 | 28.36 | 55.76 | Superiority |
| Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region, baseline disease severity and Dupilumab regimen received in parent studies. | Cochran-Mantel-Haenszel | = 0.0007 | Threshold for significance at 0.05 level. | Percentage difference | 29.7 | 2-Sided | 95 | 14.89 | 44.42 | Superiority |
| Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region, baseline disease severity and Dupilumab regimen received in parent studies. | Cochran-Mantel-Haenszel | <0.0001 | Threshold for significance at 0.05 level. | Percentage difference | 39.7 | 2-Sided | 95 | 27.42 | 51.95 | Superiority |
| Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region, baseline disease severity and Dupilumab regimen received in parent studies. | Cochran-Mantel-Haenszel | = 0.0107 | Threshold for significance at 0.05 level. | Percentage difference | -20.6 | 2-Sided | 95 | -35.32 | -5.89 | Superiority |
| Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). Analysis was performed using Cochran-Mantel-Haenszel test stratified by region, baseline disease severity and Dupilumab regimen received in parent studies. | Cochran-Mantel-Haenszel | <0.0001 | Threshold for significance at 0.05 level. | Percentage difference | -36.1 | 2-Sided | 95 | -48.40 | -23.74 | Superiority |