Atopic Dermatitis
Conditions
Brief summary
The primary objective was to assess the clinical efficacy of repeated subcutaneous (SC) doses of Dupilumab in adult participants with moderate-to-severe atopic dermatitis (AD).
Interventions
DRUGPlacebo
Subcutaneous injection altered between back of arms, abdomen and upper thighs.
DRUGDupilumab
Subcutaneous injection altered between back of arms, abdomen and upper thighs.
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The inclusion criteria included, but were not limited to the following: 1. Male or female, 18 years or older; 2. Chronic Atopic Dermatitis (AD) for at least 3 years; 3. History of inadequate response to a stable (\>/= 1 month) regimen of topical corticosteroids or calcineurin inhibitors as treatment for AD within 3 months before the screening visit.
Exclusion criteria
1. Prior treatment with REGN668; 2. Presence of certain laboratory abnormalities at the screening visit; 3. Treatment with an investigational drug within 8 weeks ; 4. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit; 5. Certain treatments and medical procedures, undertaken within a particular time-frame prior to the baseline visit, preclude eligibility for participation in the study; 6. Known history of human immunodeficiency virus (HIV) infection; 7. History of malignancy within 5 years before the baseline visit, with certain exceptions; 8. Planned surgical procedure during the length of the patient's participation in this study; 9. History of clinical parasite infection; 10. Any medical or psychiatric condition which in the opinion of the investigator or the sponsor's medical monitor, would place the participant at risk, interfere with participation in the study, or interfere with the interpretation of study results; 11. Pregnant or breast-feeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 12- Last Observation Carried Forward (LOCF) | Baseline to Week 12 | 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. The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Investigator's Global Assessment (IGA) Score of 0 or 1 at Week 12- LOCF | Week 12 | IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF. |
| Percentage of Participants Who Achieved at Least a 50% Reduction From Baseline in the EASI Score (EASI-50) at Week 12- LOCF | Week 12 | The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50 responders were the participants who achieved ≥50% overall improvement in EASI score from baseline to Week 12. The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF. |
| Change From Baseline in EASI Score at Week 12- LOCF | Baseline to Week 12 | 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. The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF. |
| Percent Change From Baseline in IGA Score at Week 12- LOCF | Baseline to Week 12 | IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF. |
| Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 12 - LOCF | Baseline to Week 12 | BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck \[9%\], anterior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], and genitals \[1%\]). It was reported as a percentage of all major body sections combined. The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF. |
| Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 12- LOCF | Baseline to Week 12 | SCORAD is a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF. |
| Change From Baseline in Pruritus Numerical Rating Scale (NRS) to Week 12- LOCF | Baseline to Week 12 | 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 \[0 = no itch; 10 = worst itch imaginable\]). The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF. |
| Change From Baseline in 5-D Pruritus Scale at Week 12 | Baseline to Week 12 | The 5-D Pruritus Scale is a 1-page, 5-question tool used in clinical trials to assess 5 dimensions of background itch: degree, duration, direction, disability, and distribution. Each question corresponds to 1 of the 5 dimensions of itch; participants were to rate their symptoms over the preceding 2-week period on a 1 to 5 scale, with 5 being the most affected. After the summation of individual score, the total score ranges from 5 (least affected) to 25 (most affected). |
Countries
Czechia, France, Germany, Hungary, Poland
Participant flow
Recruitment details
The study was conducted at 25 sites in Europe between 3 April 2012 and 25 June 2013. A total of 153 participants were screened in the study.
Pre-assignment details
Out of 153 participants, 109 were randomized and treated in the study. Participants were randomized in 1:1 ratio to receive either Dupilumab 300 mg or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo (for Dupilumab) once weekly for 12 weeks by SC injection. | 54 |
| Dupilumab 300 mg Dupilumab 300 mg once weekly for 12 weeks by SC injection. | 55 |
| Total | 109 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Inadequate response to study treatment | 23 | 7 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Other than specified above | 0 | 2 |
| Overall Study | Physician Decision | 2 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Total | Dupilumab 300 mg | Placebo |
|---|---|---|---|
| 5-D Pruritus Scale | 18.5 units on a scale STANDARD_DEVIATION 3.26 | 18.4 units on a scale STANDARD_DEVIATION 3.04 | 18.7 units on a scale STANDARD_DEVIATION 3.5 |
| Age, Continuous | 36.5 years STANDARD_DEVIATION 11.69 | 33.7 years STANDARD_DEVIATION 10.41 | 39.4 years STANDARD_DEVIATION 12.29 |
| Body Surface Area (BSA) | 48.8 percentage of BSA STANDARD_DEVIATION 24.32 | 46.8 percentage of BSA STANDARD_DEVIATION 24.55 | 50.8 percentage of BSA STANDARD_DEVIATION 24.13 |
| Eczema Area and Severity Index (EASI) Score | 29.6 units on a scale STANDARD_DEVIATION 13.59 | 28.4 units on a scale STANDARD_DEVIATION 13.57 | 30.8 units on a scale STANDARD_DEVIATION 13.63 |
| Investigator's Global Assessment (IGA) Score | 3.9 units on a scale STANDARD_DEVIATION 0.68 | 3.9 units on a scale STANDARD_DEVIATION 0.67 | 4.0 units on a scale STANDARD_DEVIATION 0.69 |
| Pruritus Numerical Rating Scale (NRS) Score | 5.9 units on a scale STANDARD_DEVIATION 1.66 | 6.1 units on a scale STANDARD_DEVIATION 1.34 | 5.8 units on a scale STANDARD_DEVIATION 1.93 |
| Scoring Atopic Dermatitis (SCORAD) Score | 67.9 units on a scale STANDARD_DEVIATION 13.59 | 66.7 units on a scale STANDARD_DEVIATION 13.82 | 69.1 units on a scale STANDARD_DEVIATION 13.38 |
| Sex: Female, Male Female | 51 Participants | 24 Participants | 27 Participants |
| Sex: Female, Male Male | 58 Participants | 31 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 54 | 38 / 55 |
| serious Total, serious adverse events | 7 / 54 | 1 / 55 |
Outcome results
Primary
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 12- Last Observation Carried Forward (LOCF)
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. The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.
Time frame: Baseline to Week 12
Population: Full analysis set (FAS) population included all randomized participants who received at least one dose of study drug and had at least 1 post-baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 12- Last Observation Carried Forward (LOCF) | -23.3 percent change | Standard Deviation 49.26 |
| Dupilumab 300 mg | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score at Week 12- Last Observation Carried Forward (LOCF) | -74.0 percent change | Standard Deviation 26.94 |
Secondary
Change From Baseline in 5-D Pruritus Scale at Week 12
The 5-D Pruritus Scale is a 1-page, 5-question tool used in clinical trials to assess 5 dimensions of background itch: degree, duration, direction, disability, and distribution. Each question corresponds to 1 of the 5 dimensions of itch; participants were to rate their symptoms over the preceding 2-week period on a 1 to 5 scale, with 5 being the most affected. After the summation of individual score, the total score ranges from 5 (least affected) to 25 (most affected).
Time frame: Baseline to Week 12
Population: FAS population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in 5-D Pruritus Scale at Week 12 | -1.9 units on a scale | Standard Deviation 4.28 |
| Dupilumab 300 mg | Change From Baseline in 5-D Pruritus Scale at Week 12 | -7.4 units on a scale | Standard Deviation 4.33 |
Secondary
Change From Baseline in EASI Score at Week 12- LOCF
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. The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.
Time frame: Baseline to Week 12
Population: FAS population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in EASI Score at Week 12- LOCF | -6.4 Units on a scale | Standard Deviation 14.85 |
| Dupilumab 300 mg | Change From Baseline in EASI Score at Week 12- LOCF | -19.9 Units on a scale | Standard Deviation 11.52 |
Secondary
Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 12 - LOCF
BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck \[9%\], anterior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], and genitals \[1%\]). It was reported as a percentage of all major body sections combined. The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.
Time frame: Baseline to Week 12
Population: FAS population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 12 - LOCF | -9.0 Percentage of BSA | Standard Deviation 21.07 |
| Dupilumab 300 mg | Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis (AD) at Week 12 - LOCF | -27.4 Percentage of BSA | Standard Deviation 22.81 |
Secondary
Change From Baseline in Pruritus Numerical Rating Scale (NRS) to Week 12- LOCF
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 \[0 = no itch; 10 = worst itch imaginable\]). The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.
Time frame: Baseline to Week 12
Population: FAS population. Number of participants analyzed = participants with available data for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Pruritus Numerical Rating Scale (NRS) to Week 12- LOCF | -0.9 units on a scale | Standard Deviation 2.07 |
| Dupilumab 300 mg | Change From Baseline in Pruritus Numerical Rating Scale (NRS) to Week 12- LOCF | -3.5 units on a scale | Standard Deviation 2 |
Secondary
Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 12- LOCF
SCORAD is a clinical tool for assessing the severity of AD developed by the European Task Force on Atopic Dermatitis (Severity scoring of atopic dermatitis: the SCORAD index). Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology (Basel) 186 (1): 23-31. 1993. Extent and intensity of eczema as well as subjective signs (insomnia, etc.) are assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease). The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.
Time frame: Baseline to Week 12
Population: FAS population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 12- LOCF | -9.8 Units on a scale | Standard Deviation 20.53 |
| Dupilumab 300 mg | Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Score at Week 12- LOCF | -35.0 Units on a scale | Standard Deviation 19.43 |
Secondary
Percentage of Participants Who Achieved at Least a 50% Reduction From Baseline in the EASI Score (EASI-50) at Week 12- LOCF
The EASI score was used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-50 responders were the participants who achieved ≥50% overall improvement in EASI score from baseline to Week 12. The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.
Time frame: Week 12
Population: FAS population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved at Least a 50% Reduction From Baseline in the EASI Score (EASI-50) at Week 12- LOCF | 35.2 Percentage of participants |
| Dupilumab 300 mg | Percentage of Participants Who Achieved at Least a 50% Reduction From Baseline in the EASI Score (EASI-50) at Week 12- LOCF | 85.5 Percentage of participants |
Secondary
Percentage of Participants With Investigator's Global Assessment (IGA) Score of 0 or 1 at Week 12- LOCF
IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.
Time frame: Week 12
Population: FAS population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Investigator's Global Assessment (IGA) Score of 0 or 1 at Week 12- LOCF | 7.4 percentage of participants |
| Dupilumab 300 mg | Percentage of Participants With Investigator's Global Assessment (IGA) Score of 0 or 1 at Week 12- LOCF | 40.0 percentage of participants |
Secondary
Percent Change From Baseline in IGA Score at Week 12- LOCF
IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). The efficacy data were set to be missing after use of rescue medication and after early termination visit for participants who prematurely discontinued study treatment. All missing values were imputed by LOCF.
Time frame: Baseline to Week 12
Population: FAS population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in IGA Score at Week 12- LOCF | -14.7 Percent change | Standard Deviation 27.37 |
| Dupilumab 300 mg | Percent Change From Baseline in IGA Score at Week 12- LOCF | -49.5 Percent change | Standard Deviation 25.94 |