Study of Dupilumab Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis

Study Overview
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Brief Summary
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To assess the efficacy of multiple dupilumab dose-regimens, compared to placebo, in adult participants with moderate-to-severe atopic dermatitis (AD).

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Ranging Study Investigating the Efficacy, Safety, Pharmacokinetic and Biomarker Profiles of Dupilumab (REGN668) Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Dupilumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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The inclusion criteria included, but were not limited to, the following: Chronic Atopic Dermatitis that had been present for at least 3 years History of inadequate response to out-patient treatment with topical medications, or for whom topical treatments were otherwise inadvisable (e.g, because of important side effects or safety risks) Willing and able to comply with all clinic visits and study-related procedures The exclusion criteria included, but were not limited to, the following: Prior treatment with dupilumab (REGN668/SAR231893) Presence of certain laboratory abnormalities at the screening visit Treatment with an investigational drug within 8 weeks of baseline visit Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit Certain other treatments and medical procedures undertaken within a particular time frame prior to the baseline visit Known history of human immunodeficiency virus (HIV) infection History of malignancy within 5 years before the baseline visit (with certain exceptions) Planned surgical procedure during the length of the study High risk of parasite infection Any other medical or psychological condition that in the opinion of the investigator or the sponsor's medical monitor, would place the participants at risk, interfere with participation in the study or interfere with interpretation of study results Pregnant or breast-feeding women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo qw<br>Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection every week (qw) from Week 1 to Week 15. | Drug: Placebo<br> <br> |
| Experimental: Dupilumab 300 mg qw<br>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection qw from Week 1 to Week 15. | Drug: Dupilumab<br> <br> * Other names: Dupixent;|
| Experimental: Dupilumab 300 mg q2w<br>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single injection of Placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab every 2 weeks (q2w) from Week 1 to Week 15. | Drug: Dupilumab<br> <br> * Other names: Dupixent;Drug: Placebo<br> <br> |
| Experimental: Dupilumab 200 mg q2w<br>Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single injection of Placebo (for Dupilumab) alternating with single 200 mg injection of Dupilumab q2w from Week 1 to Week 15. | Drug: Dupilumab<br> <br> * Other names: Dupixent;Drug: Placebo<br> <br> |
| Experimental: Dupilumab 300 mg q4w<br>Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by a single 300 mg injection of Dupilumab every 4 weeks (q4w) and Placebo (for Dupilumab) qw when Dupilumab not administered from Week 1 to Week 15. | Drug: Dupilumab<br> <br> * Other names: Dupixent;Drug: Placebo<br> <br> |
| Experimental: Dupilumab 100 mg q4w<br>Two subcutaneous injections of Dupilumab 200 mg (for a total of 400 mg) as a loading dose on Day 1, followed by a single 100 mg injection of Dupilumab q4w and Placebo (for Dupilumab) qw when Dupilumab not administered from Week 1 to Week 15. | Drug: Dupilumab<br> <br> * Other names: Dupixent;Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Eczema Area and Severity Index Score (EASI) From Baseline to Week 16 | 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. | Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. EASI-50, EASI-75 and EASI-90 responders were the participants who achieved ≥50%, ≥75% and ≥90% overall improvement in EASI score respectively from baseline to Week 16. | Week 16 | 
| 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 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). SCORAD-50, SCORAD-75 and SCORAD-90 responders were the participants who achieved ≥50%, ≥75% and ≥90% overall improvement in SCORAD score respectively from baseline to Week 16. | Week 16 | 
| Percent Change in Patient Oriented Eczema Measure (POEM) Scores From Baseline to Week 16 | POEM is a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]). | Baseline to Week 16 | 
| Absolute Change in POEM Scores From Baseline to Week 16 | POEM is a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL]). | Baseline to Week 16 | 
| Changes in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) From 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). | Baseline to Week 16 | 
| Changes in GISS Cumulative Score From 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). | Baseline to Week 16 | 
| Percentage of Participants Who Achieved Investigator's Global Assessment (IGA) Response at Week 16 | IGA is an assessment scale used to determine severity of AD and clinical response to treatment on a static 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response is an IGA score of 0 (clear) or 1 (almost clear). Values after first rescue medication were set to missing and participants with missing IGA score at Week 16 were treated as a non-responders. | Week 16 | 
| Percentage of Participants Who Achieved IGA Score Reduction of ≥2 at Week 16 | 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 success is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score reduction 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 a non-responders. | Week 16 | 
| Percent Change in Peak Weekly Averaged Pruritus Numerical Rating Scores (NRS) From Baseline to Week 16 | Pruritus NRS is an assessment tool that is used to report the intensity of participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). | Baseline to Week 16 | 
| Absolute Change in Peak Weekly Averaged Pruritus NRS From Baseline to Week 16 | Pruritus NRS is an assessment tool that is used to report the intensity of participant's pruritus (itch), both maximum and average intensity, during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]). | Baseline to Week 16 | 
| Absolute Change in EASI Score From Baseline to Week 16 | 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. | Baseline to Week 16 | 
| Percent Change in SCORing Atopic Dermatitis (SCORAD) Scores From Baseline to Week 16 | 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). | Baseline to Week 16 | 
| Absolute Change in SCORAD Scores From Baseline to Week 16 | 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). | Baseline to Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eczema