Back to resultsStudy of Dupilumab and Immune Responses in Adults With Atopic Dermatitis (AD)
Primary Purpose
Atopic Dermatitis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Dupilumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Atopic Dermatitis
Eligibility Criteria
Key Inclusion Criteria:
- Male or female adults ages 18 to 64 years with Chronic AD (according to the American Academy of Dermatology Consensus Criteria, [Eichenfeld 2004])that has been present for at least 3 years before the screening visit
- Participants with documented recent history (within 6 months before the screening visit) of inadequate response to a sufficient course of outpatient treatment with topical AD medication(s), or for whom topical AD therapies are otherwise inadvisable (e.g., because of side effects or safety risks).
- Eczema Area and Severity Index (EASI) score ≥16 at the screening visit and the baseline visit
- Investigator's Global Assessment (IGA) score ≥3 (on the 0-4 IGA scale) at the screening and baseline visits
- ≥10% body surface area (BSA) of AD involvement at the screening and baseline visits
Key Exclusion Criteria:
- Prior treatment with dupilumab (REGN668/ SAR231893)
- Patients needing >10 mg of daily prednisone (including equivalent doses of other steroids) or high dose systemic corticosteroids (≥2 mg/kg) for 14 days or longer during the 16 week treatment period of the study
- History of Guillain-Barre syndrome
- History of severe allergic reaction to either vaccine or to vaccine components including alum, thimerosal, phenol
- Patients with a severe reaction to natural rubber latex products (some packaging components of the vaccines contain rubber latex and may cause a reaction in susceptible individuals)
- Treatment with biologics within 4 months of baseline visit
- Chronic or acute infection requiring treatment with antibiotics, antivirals, antiparasitics, antifungals within 4 weeks before screening visit or superficial skin infections within 1 week of screening visit
The information listed above is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial and 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 300 mg qw
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Percentage of Participants With a Positive Response (≥4-Fold Increase) to Tetanus Toxoid (the Adacel [Tdap] Vaccine) at Week 16
A positive response was defined as a ≥ 4-fold increase from pre-vaccination at baseline in anti-tetanus immunoglobulin G (IgG) titer for participants with a pre-vaccination tetanus antibody titers ≥ 0.1 IU/ml or a titer of ≥ 0.2 IU/ml for participants with pre-vaccination titers of <0.1 IU/ml. There was no planned statistical hypothesis testing regarding the difference in immune response between the 2 treatment groups for this study, therefore no formal statistical hypothesis between groups was performed.
Secondary Outcome Measures
Percentage of Participants With a Positive Response (≥2-Fold Increase) to Tetanus Toxoid (the Adacel [Tdap] Vaccine) at Week 16
Participants with positive response defined as a ≥2-fold increase from pre-vaccination baseline in anti-tetanus IgG titer for participants with pre-vaccination tetanus antibody titers ≥0.1 IU/ml or a titer of ≥0.2 IU/ml for participants with pre-vaccination titers of <0.1 IU/ml.
Percentage of Participants With a Positive Response (SBA Antibody Titer of ≥8 for Serogroup C) to Menomune Vaccine at Week 16
A positive response to the Menomune vaccine was a serum bactericidal antibody (SBA) titer of ≥8 for serogroup C.
Percentage of Participants Achieving an 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 treatment were set to missing and participants with missing IGA scores at Week 16 were counted as non-responders.
Percentage of Participants Achieving an Eczema Area and Severity Index-50 (EASI-50) (≥50% Improvement From Baseline) 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 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 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 Achieving an Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) 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 ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 16 were considered as non-responders.
Change From Baseline in Peak Weekly Averaged Pruritis Numerical Rating Scale (NRS) Scores at Week 16
Pruritus NRS was an assessment tool that was 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]). Weekly average obtained in the 7-day period prior to the baseline visit. Values after first rescue medication use were set to missing and missing values were imputed by Last observation carried forward (LOCF).
Change From Baseline in Body Surface Area (BSA) Affected by AD at Week 16
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. 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) at 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 treatment were set to missing. Analysis was completed using MMRM model which includes treatment, randomization strata, visit, baseline value, treatment-by-visit interaction, and baseline-by-visit interaction as covariates. These results are observed results without imputation.
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.
Change in Patient Oriented Eczema Measure (POEM) Score From Baseline to Week 16
The 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.
Full Information
NCT ID
NCT02210780
First Posted
August 5, 2014
Last Updated
April 23, 2020
Sponsor
Regeneron Pharmaceuticals
Collaborators
Sanofi
1. Study Identification
Unique Protocol Identification Number
NCT02210780
Brief Title
Study of Dupilumab and Immune Responses in Adults With Atopic Dermatitis (AD)
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Study Investigating Vaccine Responses in Adults With Moderate to Severe Atopic Dermatitis Treated With Dupilumab
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
August 5, 2014 (Actual)
Primary Completion Date
September 15, 2015 (Actual)
Study Completion Date
September 15, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals
Collaborators
Sanofi
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This was a 32-week, randomized, double-blind, placebo-controlled, parallel-group study assessing immunization responses to vaccination in adults with moderate to severe atopic dermatitis who are treated with subcutaneous dupilumab.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atopic Dermatitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
194 (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 qw from Week 1 to Week 15.
Arm Title
Dupilumab 300 mg qw
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Dupilumab
Other Intervention Name(s)
REGN668, SAR231893, Dupixent
Intervention Description
Administered via subcutaneous injection.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
An inactive substance containing no medicine administered via subcutaneous injection.
Primary Outcome Measure Information:
Title
Percentage of Participants With a Positive Response (≥4-Fold Increase) to Tetanus Toxoid (the Adacel [Tdap] Vaccine) at Week 16
Description
A positive response was defined as a ≥ 4-fold increase from pre-vaccination at baseline in anti-tetanus immunoglobulin G (IgG) titer for participants with a pre-vaccination tetanus antibody titers ≥ 0.1 IU/ml or a titer of ≥ 0.2 IU/ml for participants with pre-vaccination titers of <0.1 IU/ml. There was no planned statistical hypothesis testing regarding the difference in immune response between the 2 treatment groups for this study, therefore no formal statistical hypothesis between groups was performed.
Time Frame
Week 16
Secondary Outcome Measure Information:
Title
Percentage of Participants With a Positive Response (≥2-Fold Increase) to Tetanus Toxoid (the Adacel [Tdap] Vaccine) at Week 16
Description
Participants with positive response defined as a ≥2-fold increase from pre-vaccination baseline in anti-tetanus IgG titer for participants with pre-vaccination tetanus antibody titers ≥0.1 IU/ml or a titer of ≥0.2 IU/ml for participants with pre-vaccination titers of <0.1 IU/ml.
Time Frame
Week 16
Title
Percentage of Participants With a Positive Response (SBA Antibody Titer of ≥8 for Serogroup C) to Menomune Vaccine at Week 16
Description
A positive response to the Menomune vaccine was a serum bactericidal antibody (SBA) titer of ≥8 for serogroup C.
Time Frame
Week 16
Title
Percentage of Participants Achieving an 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 treatment were set to missing and participants with missing IGA scores at Week 16 were counted as non-responders.
Time Frame
Week 16
Title
Percentage of Participants Achieving an Eczema Area and Severity Index-50 (EASI-50) (≥50% Improvement From Baseline) at Week 16
Description
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 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 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
Week 16
Title
Percentage of Participants Achieving an Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16
Description
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 ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. EASI-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 16. Values after first rescue treatment use were set to missing and participants with missing EASI score at Week 16 were considered as non-responders.
Time Frame
Week 16
Title
Change From Baseline in Peak Weekly Averaged Pruritis Numerical Rating Scale (NRS) Scores at Week 16
Description
Pruritus NRS was an assessment tool that was 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]). Weekly average obtained in the 7-day period prior to the baseline visit. Values after first rescue medication use were set to missing and missing values were imputed by Last observation carried forward (LOCF).
Time Frame
Baseline to Week 16
Title
Change From Baseline in Body Surface Area (BSA) Affected by AD at Week 16
Description
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. 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) at 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 treatment were set to missing. Analysis was completed using MMRM model which includes treatment, randomization strata, visit, baseline value, treatment-by-visit interaction, and baseline-by-visit interaction as covariates. These results are observed results without imputation.
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
Title
Change in Patient Oriented Eczema Measure (POEM) Score From Baseline to Week 16
Description
The 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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Male or female adults ages 18 to 64 years with Chronic AD (according to the American Academy of Dermatology Consensus Criteria, [Eichenfeld 2004])that has been present for at least 3 years before the screening visit
Participants with documented recent history (within 6 months before the screening visit) of inadequate response to a sufficient course of outpatient treatment with topical AD medication(s), or for whom topical AD therapies are otherwise inadvisable (e.g., because of side effects or safety risks).
Eczema Area and Severity Index (EASI) score ≥16 at the screening visit and the baseline visit
Investigator's Global Assessment (IGA) score ≥3 (on the 0-4 IGA scale) at the screening and baseline visits
≥10% body surface area (BSA) of AD involvement at the screening and baseline visits
Key Exclusion Criteria:
Prior treatment with dupilumab (REGN668/ SAR231893)
Patients needing >10 mg of daily prednisone (including equivalent doses of other steroids) or high dose systemic corticosteroids (≥2 mg/kg) for 14 days or longer during the 16 week treatment period of the study
History of Guillain-Barre syndrome
History of severe allergic reaction to either vaccine or to vaccine components including alum, thimerosal, phenol
Patients with a severe reaction to natural rubber latex products (some packaging components of the vaccines contain rubber latex and may cause a reaction in susceptible individuals)
Treatment with biologics within 4 months of baseline visit
Chronic or acute infection requiring treatment with antibiotics, antivirals, antiparasitics, antifungals within 4 weeks before screening visit or superficial skin infections within 1 week of screening visit
The information listed above is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial and 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
Birmingham
State/Province
Alabama
Country
United States
City
Fort Smith
State/Province
Arkansas
Country
United States
City
Long Beach
State/Province
California
Country
United States
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Los Angeles
State/Province
California
Country
United States
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Mission Viejo
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California
Country
United States
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Rolling Hills Estates
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California
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United States
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San Diego
State/Province
California
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United States
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Santa Monica
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California
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United States
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Denver
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Colorado
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United States
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Jacksonville
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Florida
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United States
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Miami
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Florida
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United States
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Tampa
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Florida
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United States
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Macon
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Georgia
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United States
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Chicago
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Illinois
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United States
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Maywood
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Illinois
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United States
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West Dundee
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Illinois
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United States
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Indianapolis
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Indiana
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United States
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Plainfield
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Indiana
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United States
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Overland Park
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Kansas
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Boston
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Massachusetts
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Ann Arbor
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Michigan
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United States
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Troy
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Michigan
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United States
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Saint Louis
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Missouri
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United States
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Hackensack
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New Jersey
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United States
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Albuquerque
State/Province
New Mexico
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United States
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Buffalo
State/Province
New York
Country
United States
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Forest Hills
State/Province
New York
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United States
City
New York
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New York
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United States
City
Cleveland
State/Province
Ohio
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United States
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Norman
State/Province
Oklahoma
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United States
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Tulsa
State/Province
Oklahoma
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United States
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Medford
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Oregon
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Portland
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Oregon
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Pittsburgh
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Pennsylvania
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Charleston
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South Carolina
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United States
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Greer
State/Province
South Carolina
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United States
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Arlington
State/Province
Texas
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United States
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Austin
State/Province
Texas
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United States
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Houston
State/Province
Texas
Country
United States
City
Webster
State/Province
Texas
Country
United States
City
Richmond
State/Province
Virginia
Country
United States
City
Seattle
State/Province
Washington
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of Dupilumab and Immune Responses in Adults With Atopic Dermatitis (AD)
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