Back to resultsStudy to Determine the Safety and Effectiveness of Dupilumab for Treatment of Atopic Dermatitis (AD)
Primary Purpose
Atopic Dermatitis (AD)
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Dupilumab
Placebo
Background treatment
Sponsored by
About this trial
This is an interventional treatment trial for Atopic Dermatitis (AD)
Eligibility Criteria
Inclusion Criteria:
- Male or female, 18 years or older;
- Chronic AD that had been present for at least 3 years before the screening visit;
- 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;
- Willing and able to comply with all clinic visits and study-related procedures.
Exclusion Criteria:
- Prior participation in a Dupilumab clinical trial;
- Treatment with an investigational drug within 8 weeks or within 5 half-lives before the baseline visit;
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;
- Treatment with topical corticosteroids, tacrolimus and/or pimecrolimus within 1 week before the baseline visit;
- Treatment with certain biologics;
- Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks before the baseline visit;
- Planned major surgical procedure during the participant's participation in this study;
- Participant was a member of the investigational team or his/her immediate family;
- Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit
- 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/exclusion criteria are listed.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Placebo qw
Dupilumab 200 mg qw
Arm Description
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection once weekly (qw) from Week 1 to Week 15.
Two subcutaneous injections of Dupilumab 200 milligram (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.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT01979016
First Posted
November 1, 2013
Last Updated
March 5, 2020
Sponsor
Regeneron Pharmaceuticals
Collaborators
Sanofi
1. Study Identification
Unique Protocol Identification Number
NCT01979016
Brief Title
Study to Determine the Safety and Effectiveness of Dupilumab for Treatment of Atopic Dermatitis (AD)
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Investigating the Efficacy, Safety, Serum Concentration and Biomarker Profile of Dupilumab Administered to Adult Patients With Moderate-to-Severe Atopic Dermatitis
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
December 31, 2013 (Actual)
Primary Completion Date
December 31, 2014 (Actual)
Study Completion Date
January 31, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals
Collaborators
Sanofi
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atopic Dermatitis (AD)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
54 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo qw
Arm Type
Experimental
Arm Description
Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection once weekly (qw) from Week 1 to Week 15.
Arm Title
Dupilumab 200 mg qw
Arm Type
Experimental
Arm Description
Two subcutaneous injections of Dupilumab 200 milligram (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.
Intervention Type
Drug
Intervention Name(s)
Dupilumab
Other Intervention Name(s)
REGN668, SAR231893, Dupixent
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo
Intervention Type
Other
Intervention Name(s)
Background treatment
Other Intervention Name(s)
Topical emollient
Intervention Description
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).
Primary Outcome Measure Information:
Title
Percent Change From Baseline in the Eczema Area Severity Index Score (EASI) to Week 16
Description
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
Secondary Outcome Measure Information:
Title
Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" at Week 16
Description
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
Title
Percentage of Participants Who Achieved IGA Score Reduction From Baseline of ≥2 Points at Week 16
Description
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
Title
Absolute Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16
Description
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
Title
Percent Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16
Description
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
Title
Absolute Change From Baseline in EASI Score to Week 16
Description
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
Title
Absolute Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score to Week 16
Description
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
Title
Percent Change From Baseline in SCORing Atopic Dermatitis (SCORAD) Score to Week 16
Description
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
Title
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
Description
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
Title
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
Description
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
Title
Absolute Change From Baseline in Participant's Oriented Eczema Measure (POEM) Score to Week 16
Description
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
Title
Percent Change From Baseline in Participant's Oriented Eczema Measure (POEM) Score to Week 16
Description
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
Title
Change From Baseline in Global Individual Signs Score (GISS) Components (Erythema, Infiltration/Papulation, Excoriations, and Lichenification) to Week 16
Description
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
Title
Changes From Baseline in GISS Cumulative Score to Week 16
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female, 18 years or older;
Chronic AD that had been present for at least 3 years before the screening visit;
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;
Willing and able to comply with all clinic visits and study-related procedures.
Exclusion Criteria:
Prior participation in a Dupilumab clinical trial;
Treatment with an investigational drug within 8 weeks or within 5 half-lives before the baseline visit;
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;
Treatment with topical corticosteroids, tacrolimus and/or pimecrolimus within 1 week before the baseline visit;
Treatment with certain biologics;
Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks before the baseline visit;
Planned major surgical procedure during the participant's participation in this study;
Participant was a member of the investigational team or his/her immediate family;
Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit
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/exclusion criteria are listed.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
City
Chicago
State/Province
Illinois
Country
United States
City
New York
State/Province
New York
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Montreal
State/Province
Quebec
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
31252032
Citation
Callewaert C, Nakatsuji T, Knight R, Kosciolek T, Vrbanac A, Kotol P, Ardeleanu M, Hultsch T, Guttman-Yassky E, Bissonnette R, Silverberg JI, Krueger J, Menter A, Graham NMH, Pirozzi G, Hamilton JD, Gallo RL. IL-4Ralpha Blockade by Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Atopic Dermatitis. J Invest Dermatol. 2020 Jan;140(1):191-202.e7. doi: 10.1016/j.jid.2019.05.024. Epub 2019 Jun 25.
Results Reference
derived
PubMed Identifier
30194992
Citation
Guttman-Yassky E, Bissonnette R, Ungar B, Suarez-Farinas M, Ardeleanu M, Esaki H, Suprun M, Estrada Y, Xu H, Peng X, Silverberg JI, Menter A, Krueger JG, Zhang R, Chaudhry U, Swanson B, Graham NMH, Pirozzi G, Yancopoulos GD, D Hamilton JD. Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis. J Allergy Clin Immunol. 2019 Jan;143(1):155-172. doi: 10.1016/j.jaci.2018.08.022. Epub 2018 Sep 5.
Results Reference
derived
Learn more about this trial
Study to Determine the Safety and Effectiveness of Dupilumab for Treatment of Atopic Dermatitis (AD)
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