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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02260986




Registration number
NCT02260986
Ethics application status
Date submitted
6/10/2014
Date registered
9/10/2014
Date last updated
17/10/2017

Titles & IDs
Public title
Study to Assess the Efficacy and Long-term Safety of Dupilumab (REGN668/SAR231893) in Adult Participants With Moderate-to-Severe Atopic Dermatitis
Scientific title
A Randomized, Double-Blind, Placebo-Controlled Study to Demonstrate the Efficacy and Long-Term Safety of Dupilumab in Adult Patients With Moderate-to-Severe Atopic Dermatitis
Secondary ID [1] 0 0
R668-AD-1224
Universal Trial Number (UTN)
Trial acronym
CHRONOS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atopic Dermatitis 0 0
Condition category
Condition code
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dupilumab
Treatment: Drugs - Placebo (for Dupilumab)
Other interventions - Topical Corticosteroid (TCS)

Experimental: Placebo qw - Two subcutaneous injections of Placebo (for Dupilumab) as a loading dose on Day 1 followed by a single injection weekly (qw) from Week 1 to Week 51.

Experimental: Dupilumab 300 mg q2w - Two subcutaneous injections of Dupilumab 300 mg (for a total of 600 mg) as a loading dose on Day 1, followed by placebo (for Dupilumab) alternating with single 300 mg injection of Dupilumab every 2 weeks (q2w) from Week 1 to Week 51. During weeks in which Dupilumab was not administered, participants received placebo.

Experimental: Dupilumab 300 mg qw - 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 qw from Week 1 to Week 51.


Treatment: Drugs: Dupilumab
Subcutaneous injection in the different quadrants of the abdomen (avoiding navel and waist areas) and upper thighs

Treatment: Drugs: Placebo (for Dupilumab)
Subcutaneous injection in the different quadrants of the abdomen (avoiding navel and waist areas) and upper thighs

Other interventions: Topical Corticosteroid (TCS)
All participants were required to treatment with a (TCS) using a standardized regimen. It was recommended that participants use triamcinolone acetonide 0.1% cream or fluocinolone acetonide 0.025% ointment for medium potency, and hydrocortisone 1% cream for low potency.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of =2 Points at Week 16
Timepoint [1] 0 0
Baseline to Week 16
Secondary outcome [1] 0 0
Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (=75% Improvement From Baseline) at Week 16
Timepoint [1] 0 0
Baseline to Week 16
Secondary outcome [2] 0 0
Percentage of Participants With Improvement (Reduction =4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16
Timepoint [2] 0 0
Baseline to Week 16
Secondary outcome [3] 0 0
Percentage of Participants With Improvement (Reduction =3 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16
Timepoint [3] 0 0
Baseline to Week 16
Secondary outcome [4] 0 0
Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of =2 Points at Week 52
Timepoint [4] 0 0
Baseline to Week 52
Secondary outcome [5] 0 0
Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (=75% Improvement From Baseline) at Week 52
Timepoint [5] 0 0
Baseline to Week 52
Secondary outcome [6] 0 0
Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16
Timepoint [6] 0 0
Baseline to Week 16
Secondary outcome [7] 0 0
Percentage of Participants With Improvement (Reduction =4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 52
Timepoint [7] 0 0
Baseline to Week 52
Secondary outcome [8] 0 0
Percentage of Participants With Improvement (Reduction =3 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 52
Timepoint [8] 0 0
Baseline to Week 52
Secondary outcome [9] 0 0
Percentage of Participants With Improvement (Reduction =4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 24
Timepoint [9] 0 0
Baseline to Week 24
Secondary outcome [10] 0 0
Percentage of Participants With Improvement (Reduction =4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 4
Timepoint [10] 0 0
Baseline to Week 4
Secondary outcome [11] 0 0
Percentage of Participants With Improvement (Reduction =4 Points) of Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 2
Timepoint [11] 0 0
Baseline to Week 2
Secondary outcome [12] 0 0
Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16
Timepoint [12] 0 0
Baseline to Week 16
Secondary outcome [13] 0 0
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 16
Timepoint [13] 0 0
Baseline to Week 16
Secondary outcome [14] 0 0
Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis to Week 16
Timepoint [14] 0 0
Baseline to Week 16
Secondary outcome [15] 0 0
Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 16
Timepoint [15] 0 0
Baseline to Week 16
Secondary outcome [16] 0 0
Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16
Timepoint [16] 0 0
Baseline to Week 16
Secondary outcome [17] 0 0
Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16
Timepoint [17] 0 0
Baseline to Week 16
Secondary outcome [18] 0 0
Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16
Timepoint [18] 0 0
Baseline to Week 16
Secondary outcome [19] 0 0
Percent Change From Baseline in Total Global Individual Signs Score (GISS) to Week 16
Timepoint [19] 0 0
Baseline to Week 16
Secondary outcome [20] 0 0
Proportion of Topical Atopic Dermatitis Medication-Free Days Through Week 52
Timepoint [20] 0 0
Baseline to Week 52
Secondary outcome [21] 0 0
Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 2
Timepoint [21] 0 0
Baseline to Week 2
Secondary outcome [22] 0 0
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 52
Timepoint [22] 0 0
Baseline to Week 52
Secondary outcome [23] 0 0
Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis to Week 52
Timepoint [23] 0 0
Baseline to Week 52
Secondary outcome [24] 0 0
Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 52
Timepoint [24] 0 0
Baseline to Week 52
Secondary outcome [25] 0 0
Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 52
Timepoint [25] 0 0
Baseline to Week 52
Secondary outcome [26] 0 0
Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 52
Timepoint [26] 0 0
Baseline to Week 52
Secondary outcome [27] 0 0
Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 52
Timepoint [27] 0 0
Baseline to Week 52
Secondary outcome [28] 0 0
Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 52
Timepoint [28] 0 0
Baseline to Week 52
Secondary outcome [29] 0 0
Number of Flares Through Week 52
Timepoint [29] 0 0
Baseline up to Week 52
Secondary outcome [30] 0 0
Number of Serious Treatment Emergent Adverse Events (TEAEs) Leading to Study Drug Discontinuation Through Week 52
Timepoint [30] 0 0
Baseline up to Week 52
Secondary outcome [31] 0 0
Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) From Baseline Through Week 52
Timepoint [31] 0 0
Baseline up to Week 52
Secondary outcome [32] 0 0
Number of Skin Infection TEAEs (Excluding Herpetic Infections) From Baseline Through Week 52
Timepoint [32] 0 0
Baseline up to Week 52
Secondary outcome [33] 0 0
Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Requiring Systemic Treatment From Baseline Through Week 52
Timepoint [33] 0 0
Baseline up to Week 52
Secondary outcome [34] 0 0
Number of Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Requiring Systemic Treatment From Baseline Through Week 52
Timepoint [34] 0 0
Baseline up to Week 52

Eligibility
Key inclusion criteria
Key

1. Chronic AD that had been present for at least 3 years before the screening visit;

2. Documented recent history (within 6 months before the screening visit) of inadequate
response to a sufficient course of out-patient treatment with topical AD
medication(s).

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participation in a prior Dupilumab clinical trial;

2. Important side effects of topical medication (e.g. intolerance to treatment,
hypersensitivity reactions, significant skin atrophy, systemic effects), as assessed
by the investigator or treating physician;

3. Having used any of the following treatments within 4 weeks before the baseline visit,
or any condition that, in the opinion of the investigator, was likely to require such
treatment(s) during the first 2 weeks of study treatment:

1. Immunosuppressive/immunomodulating drugs (e.g, systemic steroids, cyclosporine,
mycophenolate-mofetil, Janus kinase inhibitors, interferon-gamma [IFN-?],
azathioprine, methotrexate, etc.);

2. Phototherapy for AD;

4. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit;

5. History of human immunodeficiency virus (HIV) infection or positive HIV serology at
screening;

6. Positive hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or
hepatitis C antibody at the screening visit;

7. Active or acute infection requiring systemic treatment within 2 weeks before baseline
visit;

8. Known or suspected history of immunosuppression;

9. Pregnant or breastfeeding women, or planning to become pregnant or breastfeed during
the participant's participation in this study.

Note: The eligibility criteria 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
- Phillip
Recruitment hospital [2] 0 0
- Kogarah
Recruitment hospital [3] 0 0
- Benowa
Recruitment hospital [4] 0 0
- Dulwich
Recruitment hospital [5] 0 0
- Hectorville
Recruitment hospital [6] 0 0
- Carlton
Recruitment postcode(s) [1] 0 0
- Phillip
Recruitment postcode(s) [2] 0 0
- Kogarah
Recruitment postcode(s) [3] 0 0
- Benowa
Recruitment postcode(s) [4] 0 0
- Dulwich
Recruitment postcode(s) [5] 0 0
- Hectorville
Recruitment postcode(s) [6] 0 0
- Carlton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
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State/province [5] 0 0
Florida
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United States of America
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Georgia
Country [7] 0 0
United States of America
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Illinois
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United States of America
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Indiana
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United States of America
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Maryland
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United States of America
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Michigan
Country [11] 0 0
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Minnesota
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Missouri
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Nebraska
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United States of America
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Nevada
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New Jersey
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New Mexico
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New York
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Oklahoma
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Oregon
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Pennsylvania
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Utah
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Vermont
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Virginia
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United States of America
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Washington
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Canada
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British Columbia
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Canada
State/province [28] 0 0
Ontario
Country [29] 0 0
Canada
State/province [29] 0 0
Quebec
Country [30] 0 0
Czechia
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Hradec Kralove
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Czechia
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Nachod
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Czechia
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Praha 10
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Czechia
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Praha 5
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Czechia
State/province [34] 0 0
Svitavy
Country [35] 0 0
Czechia
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Usti nad Labem
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Hungary
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Békés
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Hungary
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Jász-Nagykun-Szolnok
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Veszprém
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Budapest
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Tokyo
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Tôkyô
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Korea, Republic of
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Gyeonggido
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Seoul Teugbyeolsi
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Seodaemun-gu
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Uijeongbu-si
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Netherlands
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Noord-Brabant
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Groningen
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Utrecht
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Auckland
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Dolnoslaskie
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Lubelskie
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Mazowieckie
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Malopolskie
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Opolskie
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Podkarpackie
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Podlaskie
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Wielkopolskie
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Zachodniopomorskie
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Gdynia
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Lódzkie
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Poland
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Slaskie
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Poland
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Swietokrzyskie
Country [80] 0 0
Romania
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Brasov
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Romania
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Bucuresti
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Romania
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Cluj
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Romania
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Dolj
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Romania
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Mures
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Spain
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Cataluña
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Spain
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Alicante
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Spain
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Madrid
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United Kingdom
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Angus
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United Kingdom
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Birmingham
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United Kingdom
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Glasgow City
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United Kingdom
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Kent
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United Kingdom
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Middlesex
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United Kingdom
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Liverpool
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United Kingdom
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Manchester
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United Kingdom
State/province [95] 0 0
Reading
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United Kingdom
State/province [96] 0 0
Salford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Regeneron Pharmaceuticals
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Sanofi
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of the study was to demonstrate the efficacy of Dupilumab administered
concomitantly with topical corticosteroid (TCS) through Week 16 in adult participants with
moderate-to-severe atopic dermatitis (AD) compared to placebo administered concomitantly with
TCS.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02260986
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trial Management
Address 0 0
Regeneron Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02260986