Atopic Dermatitis
Conditions
Brief summary
The primary objective is to assess the long-term safety of dupilumab administered in adult participants with atopic dermatitis (AD). The secondary objective of the study is to assess the immunogenicity of dupilumab in adult participants with AD, in the context of re-treatment, and to monitor efficacy parameters associated with long-term treatment. Optional Sub-Study: The primary objective of the sub-study is to assess the safety of the new dupilumab drug product in adult patients with AD after switching from the current dupilumab drug product. The secondary objectives of the sub-study are to evaluate systemic exposure and immunogenicity of the new dupilumab drug product in adult patients with AD.
Interventions
DRUGDupilumab
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Participation in a prior clinical trial of dupilumab for AD and met one of the following: 1. Received study treatment and adequately completed the assessments required for both the treatment and follow-up periods of the parent studies (except studies listed in b) as defined in the parent protocols 2. Received study treatment in one the studies that have completed last patient, last visit irrespective of duration of participation, provided that patients completed with the instructions received during the study. 3. Underwent screening in R668-AD-1334 (Liberty AD SOLO 1) or R668-AD-1416 (Liberty AD SOLO 2) but could not be randomized due to randomization closure. 2. Willing and able to comply with all clinic visits and study-related procedures 3. Able to understand and complete study-related questionnaires 4. Provide signed informed consent Optional Sub-Study: 1. Provide separate informed consent 2. Continuing in the treatment period of the main OLE study 3. Demonstrated compliance with dupilumab therapy, as defined in the protocol Key
Exclusion criteria
1. Patients who, during their participation in a previous dupilumab clinical trial, developed a serious adverse event (SAE) deemed related to dupilumab\*, which in the opinion of the investigator or of the medical monitor could indicate that continued treatment with dupilumab may present an unreasonable risk for the patient. 2. Patients who, during their participation in a previous dupilumab clinical trial, developed an AE that was deemed related to dupilumab\* and led to study treatment discontinuation, which in the opinion of the investigator or of the medical monitor could indicate that continued treatment with dupilumab may present an unreasonable risk for the patient. 3. Conditions in the previous dupilumab study consistent with protocol-defined criteria for permanent study drug discontinuation, if deemed related to dupilumab\* or led to investigator - or sponsor-initiated withdrawal of patient from the study (eg, non-compliance, inability to complete study assessments, etc.). \*Note for
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment Emergent Adverse Events (TEAEs) | Up to 272 weeks | — |
| OPTIONAL SUB-STUDY: Number of Adverse Events of Special Interest (AESIs) Through the Last Study Visit After Switching to the New Dupilumab Drug Product | Up to 24 Weeks | Adverse events of special interest in this study include: Anaphylactic reactions, Systemic hypersensitivity reactions, Helminthic infections, Any severe type of conjunctivitis or blepharitis, Keratitis, Clinically symptomatic eosinophilia (or eosinophilia associated with clinical symptoms) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of AESIs | Up to 272 weeks | Adverse events of special interest in this study include: Anaphylactic reactions, Systemic hypersensitivity reactions, Helminthic infections, Any severe type of conjunctivitis or blepharitis, Keratitis, Clinically symptomatic eosinophilia (or eosinophilia associated with clinical symptoms) |
| Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit | Up to 272 weeks (End of Study), Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study) | IGA is an assessment scale used to determine severity of hand and foot 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. |
| Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Up to 272 weeks (End of Study), Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study) | The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, induration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. |
| Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit | Up to 272 weeks (End of Study), Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study) | Low disease activity state is defined as an IGA score of ≤2 \[mild = 2, almost clear = 1, or clear = 0\] |
| Change From Baseline in EASI Score at Each Visit | Up to 272 weeks (End of Study), Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study) | The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, induration, 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. |
| Percent Change From Baseline in EASI Score at Each Visit | Up to 272 weeks (End of Study), Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study) | The EASI score was used to measure the severity and extent of atopic dermatitis (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 range from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. |
| Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Up to 272 weeks (End of Study), Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study) | EASI-50 was defined as \>=50% reduction in EASI scores from baseline of the parent study |
| Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Up to 272 weeks (End of Study), Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study) | EASI-90 was defined as \>=90% reduction in EASI scores from baseline of the parent study |
| Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study | Up to 272 weeks (End of Study), Baseline, Weeks 1, 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 252, 272 (End of Study) | The Pruritus NRS is an assessment tool for patients to report the intensity of their pruritus (itch), using a scale from 0-10, where 0 is no itch and 10 is the worst itch imaginable. Daily peak pruritus NRS score is the worst one between morning and evening scores of the day. Baseline Pruritus NRS is determined based on average of daily peak NRS scores during the 7 days immediately preceding randomization. A minimum of 4 daily scores out of 7 days is required to calculate baseline average score. Weekly worst score is calculated by taking the worst score within the week |
| Percent Change From Baseline in Pruritus NRS | Up to 272 weeks (End of Study), Baseline, Weeks 1, 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 252, 272 (End of Study) | The Pruritus NRS is an assessment tool for patients to report the intensity of their pruritus (itch), using a scale from 0-10, where 0 is no itch and 10 is the worst itch imaginable. Daily peak pruritus NRS score is the worst one between morning and evening scores of the day. Baseline Pruritus NRS is determined based on average of daily peak NRS scores during the 7 days immediately preceding randomization. A minimum of 4 daily scores out of 7 days is required to calculate baseline average score. Weekly worst score is calculated by taking the worst score within the week |
| Number of Serious Adverse Events (SAEs) of Special Interest | Up to 272 weeks | Adverse events of special interest in this study include: Anaphylactic reactions, Systemic hypersensitivity reactions, Helminthic infections, Any severe type of conjunctivitis or blepharitis, Keratitis, Clinically symptomatic eosinophilia (or eosinophilia associated with clinical symptoms) |
| Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline | Up to 272 weeks (End of Study), Baseline, Weeks 1, 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 252, 272 (End of Study) | The Pruritus NRS is an assessment tool for patients to report the intensity of their pruritus (itch), using a scale from 0-10, where 0 is no itch and 10 is the worst itch imaginable. Daily peak pruritus NRS score is the worst one between morning and evening scores of the day. Baseline Pruritus NRS is determined based on average of daily peak NRS scores during the 7 days immediately preceding randomization. A minimum of 4 daily scores out of 7 days is required to calculate baseline average score. Weekly worst score is calculated by taking the worst score within the week |
| Percentage of Participants Requiring Rescue Treatment: Overall | Up to 272 weeks | — |
| Percentage of Participants Requiring Rescue Treatment: Systemic Treatment | Up to 272 weeks | — |
| Percentage of Participants Requiring Rescue Treatment: Phototherapy | Up to 272 weeks | — |
| Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) | Up to 272 weeks (End of Study), Baseline, Weeks 12, 24, 36, 48, 76, 100, 124, 148, 272 (End of Study) | 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 format is a simple response to 10 items, which assess QOL over the past week, with an overall scoring system of 0 to 30; a high score is indicative of a poor QOL |
| Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) | Up to 272 weeks (End of Study), Baseline, Weeks 12, 24, 36, 48, 76, 100, 124, 148, 272 (End of Study) | The POEM is a 7-item, validated questionnaire used in clinical practice and clinical trials to assess disease symptoms in children and adults. The format is a response to 7 items (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) with a scoring system of 0 to 28; a high score is indicative of a poor QOL. |
| Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) | Up to 272 weeks (End of Study), Baseline, Weeks 12, 24, 36, 48, 76, 100, 124, 148, 272 (End of Study) | The EuroQOL 5-Dimension Health Questionnaire (EQ-5D) is a standardized measure of health status developed by the EuroQOL Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The minimum value for the single index utility score is -0.594 (Best imaginable health state) and the maximum value for the single index utility score is 1 (Worst imaginable health state). |
| OPTIONAL SUB-STUDY: Ctrough of Functional Dupilumab in Serum Before and After Switching to the New Dupilumab Drug Product | Up to week 12 | — |
| OPTIONAL SUB-STUDY: Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response in Patients Receiving the New Dupilumab Drug Product | Up to 24 Weeks | For participants receiving dupilumab from a new manufacturing process, ADA baseline was defined as the baseline visit in the sub-study, or at the end of the main study, dependent on available data. |
| Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline | Up to 272 weeks (End of Study), Baseline, Weeks 1, 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 252, 272 (End of Study) | The Pruritus NRS is an assessment tool for patients to report the intensity of their pruritus (itch), using a scale from 0-10, where 0 is no itch and 10 is the worst itch imaginable. Daily peak pruritus NRS score is the worst one between morning and evening scores of the day. Baseline Pruritus NRS is determined based on average of daily peak NRS scores during the 7 days immediately preceding randomization. A minimum of 4 daily scores out of 7 days is required to calculate baseline average score. Weekly worst score is calculated by taking the worst score within the week |
| Rate of AESIs | Up to 272 weeks | Rate (events per patient-year) of AESIs Adverse events of special interest in this study include: Anaphylactic reactions, Systemic hypersensitivity reactions, Helminthic infections, Any severe type of conjunctivitis or blepharitis, Keratitis, Clinically symptomatic eosinophilia (or eosinophilia associated with clinical symptoms) |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, China, Czechia, Denmark, Estonia, Finland, France, Germany, Hungary, Ireland, Italy, Japan, Lithuania, Netherlands, New Zealand, Poland, Romania, Russia, Singapore, Slovakia, South Korea, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 1297 participants completed the study and 1380 participants had withdrawn. Withdrawal from study included study terminated by the Sponsor (708), and withdrawal by the participant (375), Adverse Event (107), Lost to Follow-Up (73), Lack of Efficacy (50), Protocol Deviation (34), Pregnancy (20), Physician Decision (9), and reasons not specified (4)
Participants by arm
| Arm | Count |
|---|---|
| Dupilumab Participants received repeated doses of dupilumab | 2,677 |
| Total | 2,677 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 107 |
| Overall Study | Lack of Efficacy | 50 |
| Overall Study | Lost to Follow-up | 73 |
| Overall Study | Other | 4 |
| Overall Study | Physician Decision | 9 |
| Overall Study | Pregnancy | 20 |
| Overall Study | Protocol Deviation | 34 |
| Overall Study | Terminated by Sponsor | 708 |
| Overall Study | Withdrawal by Subject | 375 |
Baseline characteristics
| Characteristic | Dupilumab |
|---|---|
| Age, Continuous | 39.2 Years STANDARD_DEVIATION 13.42 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 94 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2532 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 51 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 541 Participants |
| Race (NIH/OMB) Black or African American | 147 Participants |
| Race (NIH/OMB) More than one race | 33 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 20 Participants |
| Race (NIH/OMB) White | 1936 Participants |
| Sex: Female, Male Female | 1066 Participants |
| Sex: Female, Male Male | 1611 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 2,677 |
| other Total, other adverse events | 1,613 / 2,677 |
| serious Total, serious adverse events | 283 / 2,677 |
Outcome results
Primary
Number of Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to 272 weeks
Population: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Number of Treatment Emergent Adverse Events (TEAEs) | 14717 Number of Events |
Primary
OPTIONAL SUB-STUDY: Number of Adverse Events of Special Interest (AESIs) Through the Last Study Visit After Switching to the New Dupilumab Drug Product
Adverse events of special interest in this study include: Anaphylactic reactions, Systemic hypersensitivity reactions, Helminthic infections, Any severe type of conjunctivitis or blepharitis, Keratitis, Clinically symptomatic eosinophilia (or eosinophilia associated with clinical symptoms)
Time frame: Up to 24 Weeks
Population: The sub-study SAF includes all patients who receive new dupilumab drug product in the sub-study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | OPTIONAL SUB-STUDY: Number of Adverse Events of Special Interest (AESIs) Through the Last Study Visit After Switching to the New Dupilumab Drug Product | 0 Events |
Secondary
Change From Baseline in EASI Score at Each Visit
The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, induration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD.
Time frame: Up to 272 weeks (End of Study), Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study)
Population: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated). Here 'n' = number of evaluable participants at the specified timeframe
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dupilumab | Change From Baseline in EASI Score at Each Visit | Week 4 | -8.59 Score on a scale | Standard Deviation 10.196 |
| Dupilumab | Change From Baseline in EASI Score at Each Visit | Week 16 | -11.89 Score on a scale | Standard Deviation 12.583 |
| Dupilumab | Change From Baseline in EASI Score at Each Visit | Week 36 | -17.32 Score on a scale | Standard Deviation 13.989 |
| Dupilumab | Change From Baseline in EASI Score at Each Visit | Week 52 | -16.46 Score on a scale | Standard Deviation 13.719 |
| Dupilumab | Change From Baseline in EASI Score at Each Visit | Week 100 | -17.99 Score on a scale | Standard Deviation 14.049 |
| Dupilumab | Change From Baseline in EASI Score at Each Visit | Week 124 | -17.68 Score on a scale | Standard Deviation 13.794 |
| Dupilumab | Change From Baseline in EASI Score at Each Visit | Week 156 | -14.23 Score on a scale | Standard Deviation 14.358 |
| Dupilumab | Change From Baseline in EASI Score at Each Visit | Week 172 | -13.23 Score on a scale | Standard Deviation 13.651 |
| Dupilumab | Change From Baseline in EASI Score at Each Visit | Week 188 | -19.24 Score on a scale | Standard Deviation 11.253 |
| Dupilumab | Change From Baseline in EASI Score at Each Visit | Week 204 | -14.50 Score on a scale | Standard Deviation 15.615 |
| Dupilumab | Change From Baseline in EASI Score at Each Visit | Week 220 | -12.75 Score on a scale | Standard Deviation 14.444 |
| Dupilumab | Change From Baseline in EASI Score at Each Visit | Week 236 | -16.69 Score on a scale | Standard Deviation 9.743 |
| Dupilumab | Change From Baseline in EASI Score at Each Visit | End of Study (Extension) | -13.14 Score on a scale | Standard Deviation 14.614 |
Secondary
Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study
The Pruritus NRS is an assessment tool for patients to report the intensity of their pruritus (itch), using a scale from 0-10, where 0 is no itch and 10 is the worst itch imaginable. Daily peak pruritus NRS score is the worst one between morning and evening scores of the day. Baseline Pruritus NRS is determined based on average of daily peak NRS scores during the 7 days immediately preceding randomization. A minimum of 4 daily scores out of 7 days is required to calculate baseline average score. Weekly worst score is calculated by taking the worst score within the week
Time frame: Up to 272 weeks (End of Study), Baseline, Weeks 1, 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 252, 272 (End of Study)
Population: The safety analysis set (SAF) includes all patients who received any study drug; it is based on the treatment received. Participants recorded Pruritus score using IVRS (Interactive Voice Recording System) at specified timepoints
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dupilumab | Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study | Week 1 | -2.86 Score on a Scale | Standard Deviation 2.492 |
| Dupilumab | Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study | Week 4 | -3.81 Score on a Scale | Standard Deviation 2.403 |
| Dupilumab | Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study | Week 16 | -4.44 Score on a Scale | Standard Deviation 2.377 |
| Dupilumab | Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study | Week 36 | -4.67 Score on a Scale | Standard Deviation 2.365 |
| Dupilumab | Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study | Week 52 | -4.76 Score on a Scale | Standard Deviation 2.371 |
| Dupilumab | Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study | Week 100 | -4.69 Score on a Scale | Standard Deviation 2.315 |
| Dupilumab | Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study | Week 124 | -4.56 Score on a Scale | Standard Deviation 2.359 |
| Dupilumab | Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study | Week 156 | -4.37 Score on a Scale | Standard Deviation 2.352 |
| Dupilumab | Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study | Week 172 | -4.64 Score on a Scale | Standard Deviation 2.256 |
| Dupilumab | Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study | Week 188 | -4.73 Score on a Scale | Standard Deviation 2.194 |
| Dupilumab | Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study | Week 204 | -4.83 Score on a Scale | Standard Deviation 2.341 |
| Dupilumab | Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study | Week 220 | -4.90 Score on a Scale | Standard Deviation 2.231 |
| Dupilumab | Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study | Week 236 | -4.81 Score on a Scale | Standard Deviation 2.308 |
| Dupilumab | Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study | Week 252 | -4.89 Score on a Scale | Standard Deviation 2.201 |
| Dupilumab | Change From Baseline in Pruritus Numerical Rating Scale (NRS) in Parent Study | Week 272 | -4.69 Score on a Scale | Standard Deviation 2.238 |
Secondary
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI)
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 format is a simple response to 10 items, which assess QOL over the past week, with an overall scoring system of 0 to 30; a high score is indicative of a poor QOL
Time frame: Up to 272 weeks (End of Study), Baseline, Weeks 12, 24, 36, 48, 76, 100, 124, 148, 272 (End of Study)
Population: Administered only to the subset of participants who fluently spoke the language for which a validated translation of the questionnaire was available, at time points according to the Schedule of Events as described in the study protocol. This included all participants who received any study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) | Baseline of Current Study | 8.5 Score on a scale | Standard Deviation 7.11 |
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) | Week 12 | -4.9 Score on a scale | Standard Deviation 5.93 |
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) | Week 24 | -6.0 Score on a scale | Standard Deviation 6.41 |
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) | Week 36 | -6.5 Score on a scale | Standard Deviation 6.51 |
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) | Week 48 | -5.6 Score on a scale | Standard Deviation 6.2 |
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) | Week 76 | -7.2 Score on a scale | Standard Deviation 6.41 |
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) | Week 100 | -7.3 Score on a scale | Standard Deviation 6.66 |
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) | Week 124 | -7.9 Score on a scale | Standard Deviation 6.4 |
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) | Week 148 | -8.3 Score on a scale | Standard Deviation 5.14 |
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Dermatology Life Quality Index (DLQI) | End of Study | -3.6 Score on a scale | Standard Deviation 7.37 |
Secondary
Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM)
The POEM is a 7-item, validated questionnaire used in clinical practice and clinical trials to assess disease symptoms in children and adults. The format is a response to 7 items (dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping) with a scoring system of 0 to 28; a high score is indicative of a poor QOL.
Time frame: Up to 272 weeks (End of Study), Baseline, Weeks 12, 24, 36, 48, 76, 100, 124, 148, 272 (End of Study)
Population: Administered only to the subset of participants who fluently speak the language for which a validated translation of the questionnaire is available. This included all participants who received any study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) | Week 12 | -7.7 Score on a scale | Standard Deviation 7.32 |
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) | Week 24 | -9.3 Score on a scale | Standard Deviation 7.44 |
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) | Week 36 | -10.0 Score on a scale | Standard Deviation 7.46 |
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) | Week 48 | -8.8 Score on a scale | Standard Deviation 7.46 |
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) | Week 76 | -11.6 Score on a scale | Standard Deviation 7.79 |
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) | Week 100 | -11.4 Score on a scale | Standard Deviation 7.3 |
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) | Week 124 | -12.7 Score on a scale | Standard Deviation 7.11 |
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) | Week 148 | -10.5 Score on a scale | Standard Deviation 6.06 |
| Dupilumab | Changes From Current Study Baseline to Prespecified Time Points Through the End of the Study: Patient Oriented Eczema Measure (POEM) | End of Study | -4.5 Score on a scale | Standard Deviation 10.91 |
Secondary
Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D)
The EuroQOL 5-Dimension Health Questionnaire (EQ-5D) is a standardized measure of health status developed by the EuroQOL Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The minimum value for the single index utility score is -0.594 (Best imaginable health state) and the maximum value for the single index utility score is 1 (Worst imaginable health state).
Time frame: Up to 272 weeks (End of Study), Baseline, Weeks 12, 24, 36, 48, 76, 100, 124, 148, 272 (End of Study)
Population: Administered only to the subset of participants who fluently speak the language for which a validated translation of the questionnaire is available. This included all participants who received any study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dupilumab | Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) | Week 12 | 0.2769 Score on a scale | Standard Deviation 0.31571 |
| Dupilumab | Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) | Week 24 | 0.3001 Score on a scale | Standard Deviation 0.32062 |
| Dupilumab | Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) | Week 36 | 0.3056 Score on a scale | Standard Deviation 0.33204 |
| Dupilumab | Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) | Week 48 | 0.2854 Score on a scale | Standard Deviation 0.31017 |
| Dupilumab | Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) | Week 76 | 0.2965 Score on a scale | Standard Deviation 0.30658 |
| Dupilumab | Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) | Week 100 | 0.3217 Score on a scale | Standard Deviation 0.33832 |
| Dupilumab | Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) | Week 124 | 0.3242 Score on a scale | Standard Deviation 0.28937 |
| Dupilumab | Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) | Week 148 | 0.3046 Score on a scale | Standard Deviation 0.26337 |
| Dupilumab | Changes From Parent Study Baseline to Prespecified Time Points Through the End of the Study: EuroQol-5D (EQ-5D) | End of Study | 0.1864 Score on a scale | Standard Deviation 0.32838 |
Secondary
Number of AESIs
Adverse events of special interest in this study include: Anaphylactic reactions, Systemic hypersensitivity reactions, Helminthic infections, Any severe type of conjunctivitis or blepharitis, Keratitis, Clinically symptomatic eosinophilia (or eosinophilia associated with clinical symptoms)
Time frame: Up to 272 weeks
Population: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Number of AESIs | 161 Events |
Secondary
Number of Serious Adverse Events (SAEs) of Special Interest
Adverse events of special interest in this study include: Anaphylactic reactions, Systemic hypersensitivity reactions, Helminthic infections, Any severe type of conjunctivitis or blepharitis, Keratitis, Clinically symptomatic eosinophilia (or eosinophilia associated with clinical symptoms)
Time frame: Up to 272 weeks
Population: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Number of Serious Adverse Events (SAEs) of Special Interest | 9 Events |
Secondary
OPTIONAL SUB-STUDY: Ctrough of Functional Dupilumab in Serum Before and After Switching to the New Dupilumab Drug Product
Time frame: Up to week 12
Population: The sub-study ADA population includes all treated patients who receive new dupilumab drug product and have at least one non-missing anti-dupilumab antibody result at any time during the sub-study period after the first dose of new dupilumab drug product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dupilumab | OPTIONAL SUB-STUDY: Ctrough of Functional Dupilumab in Serum Before and After Switching to the New Dupilumab Drug Product | Week 0 | 65.9 mg/L | Standard Deviation 40.8 |
| Dupilumab | OPTIONAL SUB-STUDY: Ctrough of Functional Dupilumab in Serum Before and After Switching to the New Dupilumab Drug Product | Week 12 | 65.4 mg/L | Standard Deviation 34.7 |
Secondary
OPTIONAL SUB-STUDY: Incidence of Treatment-emergent Anti-drug Antibody (ADA) Response in Patients Receiving the New Dupilumab Drug Product
For participants receiving dupilumab from a new manufacturing process, ADA baseline was defined as the baseline visit in the sub-study, or at the end of the main study, dependent on available data.
Time frame: Up to 24 Weeks
Population: The sub-study ADA population includes all treated patients who receive new dupilumab drug product and have at least one non-missing anti-dupilumab antibody result at any time during the sub-study period after the first dose of new dupilumab drug product. No data collected.
Secondary
Percentage of Participants Requiring Rescue Treatment: Overall
Time frame: Up to 272 weeks
Population: This included all participants who received any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Percentage of Participants Requiring Rescue Treatment: Overall | 1.7 Percentage of Participants |
Secondary
Percentage of Participants Requiring Rescue Treatment: Phototherapy
Time frame: Up to 272 weeks
Population: This included all participants who received any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Percentage of Participants Requiring Rescue Treatment: Phototherapy | 0.0747 Percentage of Participants |
Secondary
Percentage of Participants Requiring Rescue Treatment: Systemic Treatment
Time frame: Up to 272 weeks
Population: This included all participants who received any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Percentage of Participants Requiring Rescue Treatment: Systemic Treatment | 1.6 Percentage of Participants |
Secondary
Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit
EASI-50 was defined as \>=50% reduction in EASI scores from baseline of the parent study
Time frame: Up to 272 weeks (End of Study), Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study)
Population: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated). Here 'n' = number of evaluable participants at the specified timeframe
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dupilumab | Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 4 | 86.0 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 16 | 95.0 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 36 | 96.7 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 52 | 97.4 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 100 | 98.5 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 124 | 98.3 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 156 | 97.4 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 172 | 98.4 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 188 | 100 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 204 | 94.9 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 220 | 97.8 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 236 | 100 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-50 (≥50% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | End of Study (Extension) | 96.9 Percentage of Participants |
Secondary
Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit
EASI-90 was defined as \>=90% reduction in EASI scores from baseline of the parent study
Time frame: Up to 272 weeks (End of Study), Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study)
Population: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated). Here 'n' = number of evaluable participants at the specified timeframe
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dupilumab | Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 188 | 72.6 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 4 | 38.6 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 16 | 57.7 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 36 | 59.7 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 52 | 68.4 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 100 | 73.0 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 124 | 74.4 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 156 | 76.3 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 172 | 81.8 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 204 | 75.8 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 220 | 84.1 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 236 | 70.0 Percentage of Participants |
| Dupilumab | Percentage of Participants With EASI-90 (≥90% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | End of Study (Extension) | 76.2 Percentage of Participants |
Secondary
Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit
The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, induration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD.
Time frame: Up to 272 weeks (End of Study), Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study)
Population: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated). Here 'n' = number of evaluable participants at the specified timeframe
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dupilumab | Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Baseline of study | 33.4 Percentage of Participants |
| Dupilumab | Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 4 | 65.3 Percentage of Participants |
| Dupilumab | Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 16 | 82.0 Percentage of Participants |
| Dupilumab | Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 36 | 85.3 Percentage of Participants |
| Dupilumab | Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 52 | 88.8 Percentage of Participants |
| Dupilumab | Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 100 | 91.4 Percentage of Participants |
| Dupilumab | Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 124 | 92.0 Percentage of Participants |
| Dupilumab | Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 156 | 89.5 Percentage of Participants |
| Dupilumab | Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 172 | 94.1 Percentage of Participants |
| Dupilumab | Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 188 | 96.8 Percentage of Participants |
| Dupilumab | Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 204 | 90.9 Percentage of Participants |
| Dupilumab | Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 220 | 93.5 Percentage of Participants |
| Dupilumab | Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | Week 236 | 100 Percentage of Participants |
| Dupilumab | Percentage of Participants With Eczema Area and Severity Index (EASI)-75 (≥75% Reduction in EASI Scores From Baseline of the Parent Study) at Each Visit | End of Study (Extension) | 88.9 Percentage of Participants |
Secondary
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline
The Pruritus NRS is an assessment tool for patients to report the intensity of their pruritus (itch), using a scale from 0-10, where 0 is no itch and 10 is the worst itch imaginable. Daily peak pruritus NRS score is the worst one between morning and evening scores of the day. Baseline Pruritus NRS is determined based on average of daily peak NRS scores during the 7 days immediately preceding randomization. A minimum of 4 daily scores out of 7 days is required to calculate baseline average score. Weekly worst score is calculated by taking the worst score within the week
Time frame: Up to 272 weeks (End of Study), Baseline, Weeks 1, 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 252, 272 (End of Study)
Population: The safety analysis set (SAF) includes all patients who received any study drug; it is based on the treatment received. Participants recorded Pruritus score using IVRS (Interactive Voice Recording System) at specified timepoints
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline | Week 1 | 11.9 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline | Week 4 | 28.3 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline | Week 16 | 39.3 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline | Week 36 | 43.8 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline | Week 52 | 45.9 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline | Week 100 | 51.1 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline | Week 124 | 48.8 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline | Week 156 | 46.5 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline | Week 172 | 54.1 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline | Week 188 | 52.5 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline | Week 204 | 56.9 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline | Week 220 | 51.5 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline | Week 236 | 51.3 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline | Week 252 | 56.2 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥3 From Baseline | Week 272 | 50.0 Percentage of Participants |
Secondary
Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline
The Pruritus NRS is an assessment tool for patients to report the intensity of their pruritus (itch), using a scale from 0-10, where 0 is no itch and 10 is the worst itch imaginable. Daily peak pruritus NRS score is the worst one between morning and evening scores of the day. Baseline Pruritus NRS is determined based on average of daily peak NRS scores during the 7 days immediately preceding randomization. A minimum of 4 daily scores out of 7 days is required to calculate baseline average score. Weekly worst score is calculated by taking the worst score within the week
Time frame: Up to 272 weeks (End of Study), Baseline, Weeks 1, 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 252, 272 (End of Study)
Population: The safety analysis set (SAF) includes all patients who received any study drug; it is based on the treatment received. Participants recorded Pruritus score using IVRS (Interactive Voice Recording System) at specified timepoints
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline | Week 1 | 7.0 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline | Week 4 | 18.6 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline | Week 16 | 29.3 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline | Week 36 | 33.3 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline | Week 52 | 35.4 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline | Week 100 | 41.4 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline | Week 124 | 39.4 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline | Week 156 | 35.6 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline | Week 172 | 42.9 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline | Week 188 | 40.9 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline | Week 204 | 44.1 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline | Week 220 | 40.2 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline | Week 236 | 37.2 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline | Week 252 | 42.7 Percentage of Participants |
| Dupilumab | Percentage of Participants With Improvement (Reduction) of Pruritus NRS ≥4 From Baseline | Week 272 | 36.0 Percentage of Participants |
Secondary
Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit
IGA is an assessment scale used to determine severity of hand and foot 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.
Time frame: Up to 272 weeks (End of Study), Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study)
Population: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dupilumab | Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit | Week 204 | 64.4 Percentage of Participants |
| Dupilumab | Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit | Baseline of study | 12.0 Percentage of Participants |
| Dupilumab | Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit | Week 4 | 31.1 Percentage of Participants |
| Dupilumab | Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit | Week 16 | 46.7 Percentage of Participants |
| Dupilumab | Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit | Week 36 | 46.2 Percentage of Participants |
| Dupilumab | Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit | Week 52 | 53.8 Percentage of Participants |
| Dupilumab | Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit | Week 100 | 58.2 Percentage of Participants |
| Dupilumab | Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit | Week 124 | 59.6 Percentage of Participants |
| Dupilumab | Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit | Week 156 | 67.2 Percentage of Participants |
| Dupilumab | Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit | Week 172 | 71.1 Percentage of Participants |
| Dupilumab | Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit | Week 188 | 56.5 Percentage of Participants |
| Dupilumab | Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit | Week 220 | 81.2 Percentage of Participants |
| Dupilumab | Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit | Week 236 | 50.0 Percentage of Participants |
| Dupilumab | Percentage of Participants With Investigator's Global Assessment (IGA) Score = 0-1 at Each Visit | End of Study (Extension) | 67.5 Percentage of Participants |
Secondary
Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit
Low disease activity state is defined as an IGA score of ≤2 \[mild = 2, almost clear = 1, or clear = 0\]
Time frame: Up to 272 weeks (End of Study), Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study)
Population: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated). Here 'n' = number of evaluable participants at the specified timeframe
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dupilumab | Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit | Baseline of study | 34.7 Percentage of Participants |
| Dupilumab | Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit | Week 4 | 70.0 Percentage of Participants |
| Dupilumab | Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit | Week 16 | 83.0 Percentage of Participants |
| Dupilumab | Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit | Week 36 | 84.6 Percentage of Participants |
| Dupilumab | Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit | Week 52 | 89.6 Percentage of Participants |
| Dupilumab | Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit | Week 100 | 90.9 Percentage of Participants |
| Dupilumab | Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit | Week 124 | 93.1 Percentage of Participants |
| Dupilumab | Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit | Week 156 | 94.8 Percentage of Participants |
| Dupilumab | Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit | Week 172 | 96.3 Percentage of Participants |
| Dupilumab | Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit | Week 188 | 96.8 Percentage of Participants |
| Dupilumab | Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit | Week 204 | 96.0 Percentage of Participants |
| Dupilumab | Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit | Week 220 | 97.1 Percentage of Participants |
| Dupilumab | Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit | Week 236 | 90.0 Percentage of Participants |
| Dupilumab | Percentage of Participants With Low Disease Activity State (eg, IGA ≤2) at Each Visit | End of Study (Extension) | 92.6 Percentage of Participants |
Secondary
Percent Change From Baseline in EASI Score at Each Visit
The EASI score was used to measure the severity and extent of atopic dermatitis (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 range from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD.
Time frame: Up to 272 weeks (End of Study), Baseline, Weeks 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 272 (End of Study)
Population: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated). Here 'n' = number of evaluable participants at the specified timeframe
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dupilumab | Percent Change From Baseline in EASI Score at Each Visit | Week 4 | -42.02 Percent of Change | Standard Deviation 88.963 |
| Dupilumab | Percent Change From Baseline in EASI Score at Each Visit | Week 16 | -54.82 Percent of Change | Standard Deviation 316.63 |
| Dupilumab | Percent Change From Baseline in EASI Score at Each Visit | Week 36 | -60.40 Percent of Change | Standard Deviation 603.886 |
| Dupilumab | Percent Change From Baseline in EASI Score at Each Visit | Week 52 | -75.76 Percent of Change | Standard Deviation 73.014 |
| Dupilumab | Percent Change From Baseline in EASI Score at Each Visit | Week 100 | -82.61 Percent of Change | Standard Deviation 29.534 |
| Dupilumab | Percent Change From Baseline in EASI Score at Each Visit | Week 124 | -84.15 Percent of Change | Standard Deviation 27.737 |
| Dupilumab | Percent Change From Baseline in EASI Score at Each Visit | Week 156 | -83.45 Percent of Change | Standard Deviation 32.41 |
| Dupilumab | Percent Change From Baseline in EASI Score at Each Visit | Week 172 | -74.98 Percent of Change | Standard Deviation 78.138 |
| Dupilumab | Percent Change From Baseline in EASI Score at Each Visit | Week 188 | -88.72 Percent of Change | Standard Deviation 15.122 |
| Dupilumab | Percent Change From Baseline in EASI Score at Each Visit | Week 204 | -70.91 Percent of Change | Standard Deviation 74.941 |
| Dupilumab | Percent Change From Baseline in EASI Score at Each Visit | Week 220 | -30.79 Percent of Change | Standard Deviation 370.994 |
| Dupilumab | Percent Change From Baseline in EASI Score at Each Visit | Week 236 | -87.56 Percent of Change | Standard Deviation 10.851 |
| Dupilumab | Percent Change From Baseline in EASI Score at Each Visit | End of Study (Extension) | -55.44 Percent of Change | Standard Deviation 213.819 |
Secondary
Percent Change From Baseline in Pruritus NRS
The Pruritus NRS is an assessment tool for patients to report the intensity of their pruritus (itch), using a scale from 0-10, where 0 is no itch and 10 is the worst itch imaginable. Daily peak pruritus NRS score is the worst one between morning and evening scores of the day. Baseline Pruritus NRS is determined based on average of daily peak NRS scores during the 7 days immediately preceding randomization. A minimum of 4 daily scores out of 7 days is required to calculate baseline average score. Weekly worst score is calculated by taking the worst score within the week
Time frame: Up to 272 weeks (End of Study), Baseline, Weeks 1, 4, 16, 36, 52, 100, 124, 156, 172, 188, 204, 220, 236, 252, 272 (End of Study)
Population: The safety analysis set (SAF) includes all patients who received any study drug; it is based on the treatment received. Participants recorded Pruritus score using IVRS (Interactive Voice Recording System) at specified timepoints
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dupilumab | Percent Change From Baseline in Pruritus NRS | Week 220 | -51.18 Percent Change | Standard Deviation 39.244 |
| Dupilumab | Percent Change From Baseline in Pruritus NRS | Week 236 | -51.67 Percent Change | Standard Deviation 37.69 |
| Dupilumab | Percent Change From Baseline in Pruritus NRS | Week 252 | -51.01 Percent Change | Standard Deviation 47.328 |
| Dupilumab | Percent Change From Baseline in Pruritus NRS | Week 272 | -46.23 Percent Change | Standard Deviation 46.404 |
| Dupilumab | Percent Change From Baseline in Pruritus NRS | Week 1 | -9.55 Percent Change | Standard Deviation 40.989 |
| Dupilumab | Percent Change From Baseline in Pruritus NRS | Week 4 | -28.88 Percent Change | Standard Deviation 41.792 |
| Dupilumab | Percent Change From Baseline in Pruritus NRS | Week 16 | -38.96 Percent Change | Standard Deviation 47.891 |
| Dupilumab | Percent Change From Baseline in Pruritus NRS | Week 36 | -41.38 Percent Change | Standard Deviation 52.3 |
| Dupilumab | Percent Change From Baseline in Pruritus NRS | Week 52 | -46.41 Percent Change | Standard Deviation 41.912 |
| Dupilumab | Percent Change From Baseline in Pruritus NRS | Week 100 | -50.62 Percent Change | Standard Deviation 42.112 |
| Dupilumab | Percent Change From Baseline in Pruritus NRS | Week 124 | -51.47 Percent Change | Standard Deviation 39.063 |
| Dupilumab | Percent Change From Baseline in Pruritus NRS | Week 156 | -48.16 Percent Change | Standard Deviation 55.076 |
| Dupilumab | Percent Change From Baseline in Pruritus NRS | Week 172 | -50.30 Percent Change | Standard Deviation 42.907 |
| Dupilumab | Percent Change From Baseline in Pruritus NRS | Week 188 | -50.56 Percent Change | Standard Deviation 43.444 |
| Dupilumab | Percent Change From Baseline in Pruritus NRS | Week 204 | -52.53 Percent Change | Standard Deviation 43.465 |
Secondary
Rate of AESIs
Rate (events per patient-year) of AESIs Adverse events of special interest in this study include: Anaphylactic reactions, Systemic hypersensitivity reactions, Helminthic infections, Any severe type of conjunctivitis or blepharitis, Keratitis, Clinically symptomatic eosinophilia (or eosinophilia associated with clinical symptoms)
Time frame: Up to 272 weeks
Population: The safety analysis set (SAF) will include all patients who received any study drug; it is based on the treatment received (as treated).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dupilumab | Rate of AESIs | 2.762 Events per Patient-Year |