Atopic Dermatitis (AD)
Conditions
Brief summary
The primary objective of the study was to assess the efficacy of Dupilumab, compared to placebo, in adult patients with moderate-to-severe atopic dermatitis (AD).
Interventions
DRUGDupilumab
DRUGPlacebo
Matching placebo
OTHERBackground treatment
Participants were required to apply stable doses of a topical emollient (moisturizer) twice daily for at least 7 days before the baseline visit and at least 7 days after the baseline visit (day -7 to day 8).
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female, 18 years or older; 2. Chronic AD that had been present for at least 3 years before the screening visit; 3. Patients with documented recent history (within 6 months before the screening visit) of inadequate response to out-patient treatment with topical medications, or for whom topical treatments were otherwise inadvisable; 4. Willing and able to comply with all clinic visits and study-related procedures.
Exclusion criteria
1. Prior participation in a Dupilumab clinical trial; 2. Treatment with an investigational drug within 8 weeks or within 5 half-lives before the baseline visit; 3. The following treatments within 4 weeks before the baseline visit, or any condition that, in the opinion of the investigator, will likely require such treatment(s) during the first 4 weeks of study treatment: * Systemic corticosteroids; * Immunosuppressive/immunomodulating drugs; * Phototherapy for AD; 4. Treatment with topical corticosteroids, tacrolimus and/or pimecrolimus within 1 week before the baseline visit; 5. Treatment with certain biologics; 6. Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks before the baseline visit; 7. Planned major surgical procedure during the participant's participation in this study; 8. Participant was a member of the investigational team or his/her immediate family; 9. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit 10. Pregnant or breast-feeding women or women planning to become pregnant or breastfeed during the study; Note: The information listed above is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial therefore not all inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in the Eczema Area Severity Index Score (EASI) to Week 16 | Baseline to Week 16 | The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema (E), infiltration (I), excoriation (Ex) and lichenification (L) 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 medication use were set to missing and missing values imputed by last observation carried forward (LOCF). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved IGA Score Reduction From Baseline of ≥2 Points at Week 16 | Baseline to Week 16 | IGA was 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. Participants with reduction in IGA score from baseline of ≥2 points at Week 16 were reported. Values after first rescue medication were set to missing and participants with missing IGA score at Week 16 were treated as non-responders. |
| Absolute Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16 | Baseline to Week 16 | Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Values after first rescue treatment were set to missing and missing values were imputed by LOCF. |
| Percent Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16 | Baseline to Week 16 | Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Values after first rescue treatment were set to missing and missing values were imputed by LOCF. |
| Absolute Change From Baseline in EASI Score to Week 16 | Baseline to Week 16 | The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Values after first rescue medication use were set to missing and missing values were imputed by LOCF. |
| Absolute Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score to Week 16 | Baseline to Week 16 | SCORAD was a clinical tool for assessing the severity of atopic dermatitis 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 ranged from 0 (absent disease) to 103 (severe disease). Values after first rescue medication use were set to missing and missing values were imputed by LOCF. |
| Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score to Week 16 | Baseline to Week 16 | SCORAD is a clinical tool for assessing the severity of atopic dermatitis 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 medication use were set to missing and missing values were imputed by LOCF. |
| Percentage of Participants With Investigator's Global Assessment (IGA) Score of 0 or 1 at Week 16 | Week 16 | IGA was 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 was an IGA score of 0 (clear) or 1 (almost clear). Values after first rescue medication were set to missing and participants with missing IGA score at Week 16 were considered as non-responders. |
| Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Baseline to Week 16 | SCORAD was a clinical tool for assessing the severity of atopic dermatitis 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). SCORAD-50, SCORAD-75 and SCORAD-90 responders were the participants who achieved ≥50%, ≥75% and ≥90% respectively, overall improvement in SCORAD score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing SCORAD score at Week 16 were counted as non-responders. |
| Absolute Change From Baseline in Participant's Oriented Eczema Measure (POEM) Score to Week 16 | Baseline to Week 16 | 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 \[QOL\]). Values after first rescue medication use were set to missing and missing values were imputed by LOCF. |
| Percent Change From Baseline in Participant's Oriented Eczema Measure (POEM) Score to Week 16 | Baseline to Week 16 | POEM was 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 medication use were set to missing and missing values were imputed by LOCF. |
| Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) to Week 16 | Baseline to Week 16 | Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease).Values after first rescue medication use were set to missing and missing values were imputed by LOCF. |
| Changes From Baseline in GISS Cumulative Score to Week 16 | Baseline to Week 16 | Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease).Values after first rescue medication use were set to missing and missing values were imputed by LOCF. |
| Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score ( EASI-50, EASI-75, and EASI-90 Respectively) at Week 16 | Baseline to Week 16 | 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 ranged from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50, EASI-75 and EASI-90 responders were the participants who achieved ≥50%, ≥75% and ≥90% respectively, overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing EASI score at Week 16 were counted as non-responders. |
Countries
Canada, United States
Participant flow
Recruitment details
The study was conducted at 5 sites in USA and Canada between 05 December 2013 and 30 January 2015. A total of 66 participants were screened in the study.
Pre-assignment details
Out of 66 participants, 54 participants were randomized and treated in the study. Participants were randomized in 1:1 ratio to receive Dupilumab 200 mg once weekly (qw) or placebo qw.
Participants by arm
| Arm | Count |
|---|---|
| Placebo qw Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection qw from Week 1 to Week 15. | 27 |
| Dupilumab 200 mg qw Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 200 mg injection qw from Week 1 to Week 15. | 27 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Dupilumab 200 mg qw | Placebo qw |
|---|---|---|---|
| Age, Continuous | 41.3 years STANDARD_DEVIATION 14.81 | 38.5 years STANDARD_DEVIATION 13.55 | 44.1 years STANDARD_DEVIATION 15.73 |
| Body Surface Area (BSA) Involvement with Atopic Dermatitis | 54.2 Percentage of BSA STANDARD_DEVIATION 28.08 | 53.8 Percentage of BSA STANDARD_DEVIATION 29.72 | 54.5 Percentage of BSA STANDARD_DEVIATION 26.91 |
| Dermatology Life Quality Index (DLQI) Score | 16.0 Units on a scale STANDARD_DEVIATION 7.38 | 17.0 Units on a scale STANDARD_DEVIATION 7.67 | 14.9 Units on a scale STANDARD_DEVIATION 7.05 |
| Eczema Area and Severity Index (EASI) Score | 33.8 units on a scale STANDARD_DEVIATION 14.87 | 33.4 units on a scale STANDARD_DEVIATION 15.41 | 34.2 units on a scale STANDARD_DEVIATION 14.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants | 26 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Global Individual Signs Score (GISS) Total Score | 8.6 units on a scale STANDARD_DEVIATION 1.76 | 8.4 units on a scale STANDARD_DEVIATION 1.82 | 8.9 units on a scale STANDARD_DEVIATION 1.69 |
| Investigator Global Assessment (IGA) Score | 3.5 units on a scale STANDARD_DEVIATION 0.5 | 3.5 units on a scale STANDARD_DEVIATION 0.51 | 3.5 units on a scale STANDARD_DEVIATION 0.51 |
| Patient Oriented Eczema Measure (POEM) Score | 21.6 units on a scale STANDARD_DEVIATION 5.52 | 21.7 units on a scale STANDARD_DEVIATION 5.55 | 21.4 units on a scale STANDARD_DEVIATION 5.6 |
| Race/Ethnicity, Customized Asian | 8 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 39 Participants | 19 Participants | 20 Participants |
| SCORing Atopic Dermatitis (SCORAD) Score | 64.6 Units on a scale STANDARD_DEVIATION 15.52 | 64.2 Units on a scale STANDARD_DEVIATION 17.67 | 65.1 Units on a scale STANDARD_DEVIATION 13.36 |
| Sex: Female, Male Female | 24 Participants | 11 Participants | 13 Participants |
| Sex: Female, Male Male | 30 Participants | 16 Participants | 14 Participants |
| Total Hospital Anxiety Depression Scale (HADS) | 13.0 Units on a scale STANDARD_DEVIATION 7.13 | 13.3 Units on a scale STANDARD_DEVIATION 7.66 | 12.7 Units on a scale STANDARD_DEVIATION 6.7 |
| Weekly Peak Pruritus Numeric Rating Scale (NRS) | 7.3 units on a scale STANDARD_DEVIATION 2.22 | 7.1 units on a scale STANDARD_DEVIATION 2.42 | 7.4 units on a scale STANDARD_DEVIATION 2.04 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 27 |
| other Total, other adverse events | 17 / 27 | 20 / 27 |
| serious Total, serious adverse events | 3 / 27 | 0 / 27 |
Outcome results
Primary
Percent Change From Baseline in the Eczema Area Severity Index Score (EASI) to Week 16
The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema (E), infiltration (I), excoriation (Ex) and lichenification (L) 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 medication use were set to missing and missing values imputed by last observation carried forward (LOCF).
Time frame: Baseline to Week 16
Population: Full analysis set (FAS) population that included all participants who were randomized into this study and received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo qw | Percent Change From Baseline in the Eczema Area Severity Index Score (EASI) to Week 16 | -5.8 percent change | Standard Error 8.16 |
| Dupilumab 200 mg qw | Percent Change From Baseline in the Eczema Area Severity Index Score (EASI) to Week 16 | -75.2 percent change | Standard Error 8.15 |
Comparison: Analysis was performed by a mixed model repeated measures (MMRM) model.p-value: <0.000195% CI: [-92.5, -46.2]ANCOVA
Secondary
Absolute Change From Baseline in EASI Score to Week 16
The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. Values after first rescue medication use were set to missing and missing values were imputed by LOCF.
Time frame: Baseline to Week 16
Population: FAS population was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo qw | Absolute Change From Baseline in EASI Score to Week 16 | -3.7 units on a scale | Standard Error 2.65 |
| Dupilumab 200 mg qw | Absolute Change From Baseline in EASI Score to Week 16 | -25.2 units on a scale | Standard Error 2.65 |
Comparison: Analysis was performed by a MMRM model.p-value: <0.000195% CI: [-29, -14]ANCOVA
Secondary
Absolute Change From Baseline in Participant's Oriented Eczema Measure (POEM) Score to Week 16
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 \[QOL\]). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.
Time frame: Baseline to Week 16
Population: FAS population was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo qw | Absolute Change From Baseline in Participant's Oriented Eczema Measure (POEM) Score to Week 16 | -2.6 units on a scale | Standard Error 1.34 |
| Dupilumab 200 mg qw | Absolute Change From Baseline in Participant's Oriented Eczema Measure (POEM) Score to Week 16 | -13.1 units on a scale | Standard Error 1.37 |
Comparison: Analysis was performed by a MMRM model.p-value: <0.000195% CI: [-14.3, -6.6]ANCOVA
Secondary
Absolute Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16
Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Values after first rescue treatment were set to missing and missing values were imputed by LOCF.
Time frame: Baseline to Week 16
Population: Analysis was performed on FAS. Here, number of participants analyzed = participants with available data for this endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo qw | Absolute Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16 | -0.98 units on a scale | Standard Error 0.398 |
| Dupilumab 200 mg qw | Absolute Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16 | -3.64 units on a scale | Standard Error 0.405 |
Comparison: Analysis was performed by a MMRM model.p-value: <0.000195% CI: [-3.8, -1.52]ANCOVA
Secondary
Absolute Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score to Week 16
SCORAD was a clinical tool for assessing the severity of atopic dermatitis 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 ranged from 0 (absent disease) to 103 (severe disease). Values after first rescue medication use were set to missing and missing values were imputed by LOCF.
Time frame: Baseline to Week 16
Population: FAS population was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo qw | Absolute Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score to Week 16 | -5.1 units on a scale | Standard Error 3.6 |
| Dupilumab 200 mg qw | Absolute Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score to Week 16 | -36.4 units on a scale | Standard Error 3.6 |
Comparison: Analysis was performed by a MMRM model.p-value: <0.000195% CI: [-41.5, -21.1]ANCOVA
Secondary
Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) to Week 16
Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease).Values after first rescue medication use were set to missing and missing values were imputed by LOCF.
Time frame: Baseline to Week 16
Population: FAS population was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo qw | Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) to Week 16 | Change in Erythema GISS | 0.0 units on a scale | Standard Error 0.14 |
| Placebo qw | Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) to Week 16 | Change in Infiltration/Papulation GISS | -0.1 units on a scale | Standard Error 0.13 |
| Placebo qw | Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) to Week 16 | Change in Excoriation GISS | -0.3 units on a scale | Standard Error 0.14 |
| Placebo qw | Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) to Week 16 | Change in Lichenification GISS | -0.1 units on a scale | Standard Error 0.14 |
| Dupilumab 200 mg qw | Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) to Week 16 | Change in Lichenification GISS | -1.2 units on a scale | Standard Error 0.14 |
| Dupilumab 200 mg qw | Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) to Week 16 | Change in Erythema GISS | -0.7 units on a scale | Standard Error 0.14 |
| Dupilumab 200 mg qw | Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) to Week 16 | Change in Excoriation GISS | -1.3 units on a scale | Standard Error 0.14 |
| Dupilumab 200 mg qw | Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) to Week 16 | Change in Infiltration/Papulation GISS | -1.0 units on a scale | Standard Error 0.13 |
Secondary
Changes From Baseline in GISS Cumulative Score to Week 16
Individual components of the AD lesions (erythema, infiltration/papulation, excoriations, and lichenification) were rated globally (each assessed for the whole body, not by anatomical region) on a 4-point scale (0 = none, 1 = mild, 2 = moderate and 3 = severe) using the EASI severity grading criteria. Total score ranges from 0 (absent disease) to 12 (severe disease).Values after first rescue medication use were set to missing and missing values were imputed by LOCF.
Time frame: Baseline to Week 16
Population: FAS population was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo qw | Changes From Baseline in GISS Cumulative Score to Week 16 | -0.5 units on a scale | Standard Error 0.46 |
| Dupilumab 200 mg qw | Changes From Baseline in GISS Cumulative Score to Week 16 | -4.2 units on a scale | Standard Error 0.46 |
p-value: <0.000195% CI: [-5.02, -2.39]ANCOVA
Secondary
Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score ( EASI-50, EASI-75, and EASI-90 Respectively) at Week 16
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 ranged from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50, EASI-75 and EASI-90 responders were the participants who achieved ≥50%, ≥75% and ≥90% respectively, overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing EASI score at Week 16 were counted as non-responders.
Time frame: Baseline to Week 16
Population: FAS population was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score ( EASI-50, EASI-75, and EASI-90 Respectively) at Week 16 | Participants with EASI-50 | 22.2 percentage of participants |
| Placebo qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score ( EASI-50, EASI-75, and EASI-90 Respectively) at Week 16 | Participants with EASI-75 | 14.8 percentage of participants |
| Placebo qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score ( EASI-50, EASI-75, and EASI-90 Respectively) at Week 16 | Participants with EASI-90 | 0 percentage of participants |
| Dupilumab 200 mg qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score ( EASI-50, EASI-75, and EASI-90 Respectively) at Week 16 | Participants with EASI-50 | 77.8 percentage of participants |
| Dupilumab 200 mg qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score ( EASI-50, EASI-75, and EASI-90 Respectively) at Week 16 | Participants with EASI-75 | 66.7 percentage of participants |
| Dupilumab 200 mg qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in EASI Score ( EASI-50, EASI-75, and EASI-90 Respectively) at Week 16 | Participants with EASI-90 | 33.3 percentage of participants |
Comparison: Statistical comparison for percentage of participants who achieved 50% reduction from baseline in EASI score (EASI-50). Analysis was performed by a MMRM model.p-value: <0.000195% CI: [33.38, 77.73]Cochran-Mantel-Haenszel
Comparison: Statistical comparison for percentage of participants who achieved 75% reduction from baseline in EASI score (EASI-75). Analysis was performed by a MMRM model.p-value: =0.000195% CI: [29.59, 74.12]Cochran-Mantel-Haenszel
Comparison: Statistical comparison for percentage of participants who achieved 90% reduction from baseline in EASI score (EASI-90). Analysis was performed by a MMRM model.p-value: =0.001195% CI: [15.55, 51.11]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16
SCORAD was a clinical tool for assessing the severity of atopic dermatitis 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). SCORAD-50, SCORAD-75 and SCORAD-90 responders were the participants who achieved ≥50%, ≥75% and ≥90% respectively, overall improvement in SCORAD score from baseline to Week 16. Values after first rescue treatment were set to missing and participants with missing SCORAD score at Week 16 were counted as non-responders.
Time frame: Baseline to Week 16
Population: FAS population was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Participants with SCORAD-50 | 7.4 percentage of participants |
| Placebo qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Participants with SCORAD-75 | 0 percentage of participants |
| Placebo qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Participants with SCORAD-90 | 0 percentage of participants |
| Dupilumab 200 mg qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Participants with SCORAD-50 | 55.6 percentage of participants |
| Dupilumab 200 mg qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Participants with SCORAD-75 | 11.1 percentage of participants |
| Dupilumab 200 mg qw | Percentage of Participants Who Achieved 50%, 75% and 90% Reduction From Baseline in SCORAD Score (SCORAD-50, SCORAD-75 and SCORAD-90 Respectively) at Week 16 | Participants with SCORAD-90 | 7.4 percentage of participants |
Comparison: Statistical comparison for percentage of participants who achieved 50% reduction from baseline in SCORAD Score (SCORAD-50). Analysis was performed by a MMRM model.p-value: =0.000295% CI: [27, 69.3]Cochran-Mantel-Haenszel
Comparison: Statistical comparison for percentage of participants who achieved 75% reduction from baseline in SCORAD Score (SCORAD-75). Analysis was performed by a MMRM model.p-value: =0.079295% CI: [-0.7, 23]Cochran-Mantel-Haenszel
Comparison: Statistical comparison for percentage of participants who achieved 90% reduction from baseline in SCORAD Score (SCORAD-90). Analysis was performed by a MMRM model.p-value: =0.157395% CI: [-2.5, 17.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved IGA Score Reduction From Baseline of ≥2 Points at Week 16
IGA was 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. Participants with reduction in IGA score from baseline of ≥2 points at Week 16 were reported. Values after first rescue medication were set to missing and participants with missing IGA score at Week 16 were treated as non-responders.
Time frame: Baseline to Week 16
Population: FAS population was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo qw | Percentage of Participants Who Achieved IGA Score Reduction From Baseline of ≥2 Points at Week 16 | 3.7 percentage of participants |
| Dupilumab 200 mg qw | Percentage of Participants Who Achieved IGA Score Reduction From Baseline of ≥2 Points at Week 16 | 51.9 percentage of participants |
Comparison: Analysis was performed by a MMRM model.p-value: <0.000195% CI: [28, 68.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Investigator's Global Assessment (IGA) Score of 0 or 1 at Week 16
IGA was 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 was an IGA score of 0 (clear) or 1 (almost clear). Values after first rescue medication were set to missing and participants with missing IGA score at Week 16 were considered as non-responders.
Time frame: Week 16
Population: FAS population was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo qw | Percentage of Participants With Investigator's Global Assessment (IGA) Score of 0 or 1 at Week 16 | 0 percentage of participants |
| Dupilumab 200 mg qw | Percentage of Participants With Investigator's Global Assessment (IGA) Score of 0 or 1 at Week 16 | 37.0 percentage of participants |
Comparison: Analysis was performed by a MMRM model.p-value: =0.000695% CI: [18.82, 55.25]Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in Participant's Oriented Eczema Measure (POEM) Score to Week 16
POEM was 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 medication use were set to missing and missing values were imputed by LOCF.
Time frame: Baseline to Week 16
Population: FAS population was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo qw | Percent Change From Baseline in Participant's Oriented Eczema Measure (POEM) Score to Week 16 | -12.1 percent change | Standard Error 6.18 |
| Dupilumab 200 mg qw | Percent Change From Baseline in Participant's Oriented Eczema Measure (POEM) Score to Week 16 | -58.3 percent change | Standard Error 6.31 |
Comparison: Analysis was performed by a MMRM model.p-value: <0.000195% CI: [-63.9, -28.5]ANCOVA
Secondary
Percent Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16
Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 \[0 = no itch; 10 = worst itch imaginable\]). Values after first rescue treatment were set to missing and missing values were imputed by LOCF.
Time frame: Baseline to Week 16
Population: FAS population. Here, number of participants analyzed = participants with available data for this endpoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo qw | Percent Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16 | -8.36 percent change | Standard Error 8.098 |
| Dupilumab 200 mg qw | Percent Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16 | -56.44 percent change | Standard Error 8.248 |
Comparison: Analysis was performed by a MMRM model.p-value: =0.000195% CI: [-71.31, -24.85]ANCOVA
Secondary
Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score to Week 16
SCORAD is a clinical tool for assessing the severity of atopic dermatitis 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 medication use were set to missing and missing values were imputed by LOCF.
Time frame: Baseline to Week 16
Population: FAS Population was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo qw | Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score to Week 16 | -8.2 percent change | Standard Error 5.41 |
| Dupilumab 200 mg qw | Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score to Week 16 | -54.8 percent change | Standard Error 5.4 |
Comparison: Analysis was performed by MMRM model.p-value: <0.000195% CI: [-62, -31.3]ANCOVA