Study to Assess the Efficacy and Long-term Safety of Dupilumab (REGN668/SAR231893) in Adult Participants With Moderate-to-Severe Atopic Dermatitis (CHRONOS)

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

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.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Placebo (for Dupilumab); Other: Topical Corticosteroid (TCS); Drug: Dupilumab

• Study Type: Interventional
• Enrollment (Actual): 740
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Phillip, Australian Capital Territory, Australia
  • New South Wales
    • Kogarah, New South Wales, Australia
  • Queensland
    • Benowa, Queensland, Australia
    • Dulwich, Queensland, Australia
  • South Australia
    • Hectorville, South Australia, Australia
  • Victoria
    • Carlton, Victoria, Australia
• Canada
  • Quebec, Canada
  • British Columbia
    • Surrey, British Columbia, Canada
    • Vancouver, British Columbia, Canada
  • Ontario
    • Ajax, Ontario, Canada
    • Barrie, Ontario, Canada
    • Hamilton, Ontario, Canada
    • Markham, Ontario, Canada
    • North Bay, Ontario, Canada
    • Oakville, Ontario, Canada
    • Ottawa, Ontario, Canada
    • Peterborough, Ontario, Canada
    • Richmond Hill, Ontario, Canada
    • Toronto, Ontario, Canada
    • Waterloo, Ontario, Canada
    • Windsor, Ontario, Canada
  • Quebec
    • Drummondville, Quebec, Canada
• Czechia
  • Hradec Kralove, Czechia
  • Nachod, Czechia
  • Praha 10, Czechia
  • Praha 5, Czechia
  • Svitavy, Czechia
  • Usti nad Labem, Czechia
• Hungary
  • Budapest, Hungary
  • Békés
    • Oroshaza, Békés, Hungary
  • Jász-Nagykun-Szolnok
    • Szolnok, Jász-Nagykun-Szolnok, Hungary
  • Veszprém
    • Veszprem, Veszprém, Hungary
• Italy
  • Ancona, Italy
  • Bologna, Italy
  • Brescia, Italy
  • Novara, Italy
  • Pavia, Italy
  • Perugia, Italy
  • Roma, Italy
• Japan
  • Fukuoka, Japan
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan
  • Hyôgo
    • Amagasaki, Hyôgo, Japan
  • Kanagawa
    • Yokohama, Kanagawa, Japan
  • Kumamoto
    • Kamimashiki-gun, Kumamoto, Japan
  • Saitama
    • Saitama-shi, Saitama, Japan
  • Shizuoka
    • Yaizu, Shizuoka, Japan
  • Tokyo
    • Koto-ku, Tokyo, Japan
    • Setagaya-ku, Tokyo, Japan
  • Tôkyô
    • Adachi-ku, Tôkyô, Japan
    • Chiyoda-ku, Tôkyô, Japan
    • Nakano-ku, Tôkyô, Japan
    • Nerima-ku, Tôkyô, Japan
    • Shibuya-ku, Tôkyô, Japan
    • Shinagawa-ku, Tôkyô, Japan
    • Shinjuku-ku, Tôkyô, Japan
    • Suginami-ku, Tôkyô, Japan
• Korea, Republic of
  • Seodaemun-gu, Korea, Republic of
  • Uijeongbu-si, Korea, Republic of
  • Gyeonggido
    • Bucheon-si, Gyeonggido, Korea, Republic of
    • Suwon, Gyeonggido, Korea, Republic of
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of
• Netherlands
  • Groningen, Netherlands
  • Utrecht, Netherlands
  • Noord-Brabant
    • Breda, Noord-Brabant, Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands
• New Zealand
  • Auckland, New Zealand
  • South Island
    • Dunedin, South Island, New Zealand
• Poland
  • Gdynia, Poland
  • Dolnośląskie
    • Wroclaw, Dolnośląskie, Poland
  • Lubelskie
    • Lublin, Lubelskie, Poland
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland
  • Małopolskie
    • Krakow, Małopolskie, Poland
  • Opolskie
    • Strzelce Opolskie, Opolskie, Poland
  • Podkarpackie
    • Iwonicz Zdroj, Podkarpackie, Poland
  • Podlaskie
    • Bialystok, Podlaskie, Poland
  • Pomorskie
    • Gdansk, Pomorskie, Poland
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland
  • Łódzkie
    • Łódź, Łódzkie, Poland
  • Śląskie
    • Katowice, Śląskie, Poland
  • Świętokrzyskie
    • Skarzysko-Kamienna, Świętokrzyskie, Poland
• Romania
  • Braşov
    • Brasov, Braşov, Romania
  • Bucureşti
    • Bucuresti, Bucureşti, Romania
  • Cluj
    • Cluj-Napoca, Cluj, Romania
  • Dolj
    • Craiova, Dolj, Romania
  • Mureş
    • Targu Mures, Mureş, Romania
• Spain
  • Alicante, Spain
  • Madrid, Spain
  • Cataluña
    • Barcelona, Cataluña, Spain
• United Kingdom
  • Liverpool, United Kingdom
  • Manchester, United Kingdom
  • Reading, United Kingdom
  • Salford, United Kingdom
  • Angus
    • Dundee, Angus, United Kingdom
  • Birmingham
    • Edgbaston, Birmingham, United Kingdom
  • Glasgow City
    • Glasgow, Glasgow City, United Kingdom
  • Kent
    • Sidcup, Kent, United Kingdom
  • Middlesex
    • Northwood, Middlesex, United Kingdom
• United States
  • Arizona
    • Phoenix, Arizona, United States
  • Arkansas
    • Hot Springs, Arkansas, United States
    • Little Rock, Arkansas, United States
  • California
    • Encinitas, California, United States
    • Oceanside, California, United States
    • Palmdale, California, United States
    • San Diego, California, United States
  • Connecticut
    • New Haven, Connecticut, United States
    • Trumbull, Connecticut, United States
  • Florida
    • Edgewater, Florida, United States
    • Lake Worth, Florida, United States
    • Miami Lakes, Florida, United States
    • Orlando, Florida, United States
    • Tampa, Florida, United States
  • Georgia
    • Alpharetta, Georgia, United States
    • Columbus, Georgia, United States
    • Savannah, Georgia, United States
  • Illinois
    • West Dundee, Illinois, United States
  • Indiana
    • Carmel, Indiana, United States
    • New Albany, Indiana, United States
  • Maryland
    • Rockville, Maryland, United States
  • Michigan
    • Ann Arbor, Michigan, United States
    • Bay City, Michigan, United States
  • Minnesota
    • Edina, Minnesota, United States
    • Fridley, Minnesota, United States
  • Missouri
    • Saint Louis, Missouri, United States
  • Nebraska
    • Omaha, Nebraska, United States
  • Nevada
    • Henderson, Nevada, United States
  • New Jersey
    • Verona, New Jersey, United States
  • New Mexico
    • Albuquerque, New Mexico, United States
  • New York
    • Corning, New York, United States
    • New York, New York, United States
    • Smithtown, New York, United States
    • Stony Brook, New York, United States
  • Ohio
    • Cincinnati, Ohio, United States
  • Oklahoma
    • Norman, Oklahoma, United States
    • Oklahoma City, Oklahoma, United States
  • Oregon
    • Lake Oswego, Oregon, United States
    • Portland, Oregon, United States
  • Pennsylvania
    • Exton, Pennsylvania, United States
    • Hazleton, Pennsylvania, United States
    • Philadelphia, Pennsylvania, United States
  • Texas
    • Austin, Texas, United States
    • Dallas, Texas, United States
  • Utah
    • West Jordan, Utah, United States
  • Vermont
    • South Burlington, Vermont, United States
  • Virginia
    • Henrico, Virginia, United States
    • Norfolk, Virginia, United States
    • Richmond, Virginia, United States
  • Washington
    • Spokane, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

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 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-γ], 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Placebo (for Dupilumab); Subcutaneous injection in the different quadrants of the abdomen (avoiding navel and waist areas) and upper thighs; Other: 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.
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.	Drug: Placebo (for Dupilumab); Subcutaneous injection in the different quadrants of the abdomen (avoiding navel and waist areas) and upper thighs; Other: 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.; Drug: Dupilumab; Subcutaneous injection in the different quadrants of the abdomen (avoiding navel and waist areas) and upper thighs; Other Names: Dupixent; REGN668; SAR231893
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.	Other: 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.; Drug: Dupilumab; Subcutaneous injection in the different quadrants of the abdomen (avoiding navel and waist areas) and upper thighs; Other Names: Dupixent; REGN668; SAR231893

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of ≥2 Points 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 response is an IGA score of 0 (clear) or 1 (almost clear). Participants with IGA score "0" or "1" and a reduction from baseline of ≥2 points at Week 16 were reported.	Baseline to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Eczema Area and Severity Index (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.	Baseline to Week 16
Percentage of Participants With 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.	Baseline to Week 16
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	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]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported.	Baseline to Week 16
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	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]). Participants achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 16 were reported.	Baseline to Week 16
Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of ≥2 Points at Week 52	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). Participants with IGA score of "0" or "1" and a reduction from baseline of ≥2 points at Week 52 were reported.	Baseline to Week 52
Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 52	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-75 responders were the participants who achieved ≥75% overall improvement in EASI score from baseline to Week 52.	Baseline to Week 52
Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to 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]).	Baseline to Week 16
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	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]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 52 were reported.	Baseline to Week 52
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	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]). Participants achieving a reduction of ≥3 points from baseline in weekly average of peak daily pruritus NRS score at Week 52 were reported.	Baseline to Week 52
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	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]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 24 were reported.	Baseline to Week 24
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	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]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 4 were reported.	Baseline to Week 4
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	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]). Participants achieving a reduction of ≥4 points from baseline in weekly average of peak daily pruritus NRS score at Week 2 were reported.	Baseline to Week 2
Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to 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]).	Baseline to Week 16
Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis to 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.	Baseline to Week 16
Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 16	SCORAD was 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.) were assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease).	Baseline to Week 16
Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16	The DLQI was a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The 10 questions assessed QOL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score was indicative of a poor QOL.	Baseline to Week 16
Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16	The 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]).	Baseline to Week 16
Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16	HADS is a fourteen item scale. Seven of the items relate to anxiety and seven items relate to depression. Each item on the questionnaire scored from 0 (minimum score) - 3 (maximum score) and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported as 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression.	Baseline to Week 16
Percent Change From Baseline in Total Global Individual Signs Score (GISS) 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
Proportion of Topical Atopic Dermatitis Medication-Free Days Through Week 52	Proportion of topical AD medication-free days through Week 52 was calculated as the number of days that a participant used neither topical corticosteroid (TCS)/ topical calcineurin inhibitors (TCI) nor system rescue therapy divided by the study days of each period.	Baseline to Week 52
Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 2	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]).	Baseline to Week 2
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 52	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.	Baseline to Week 52
Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis to Week 52	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.	Baseline to Week 52
Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 52	SCORAD was 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.) were assessed and scored. Total score ranges from 0 (absent disease) to 103 (severe disease).	Baseline to Week 52
Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 52	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 52
Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 52	The DLQI was a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life (QOL). The 10 questions assessed QOL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease); a high score was indicative of a poor QOL.	Baseline to Week 52
Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 52	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]).	Baseline to Week 52
Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 52	HADS is a fourteen item scale. Seven of the items relate to anxiety and seven items relate to depression. Each item on the questionnaire is scored from 0 (minimum score) - 3 (maximum score) and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported as 7 to 8 for possible presence, 10 to 11 for probable presence, and 14 to 15 for severe anxiety or depression.	Baseline to Week 52
Number of Flares Through Week 52	Atopic dermatitis (AD) flares were defined as worsening of the disease that required escalation/intensification of AD treatment. Number of flares occurred in the participants starting from first dose through Week 52 were reported.	Baseline up to Week 52
Number of Serious Treatment Emergent Adverse Events (TEAEs) Leading to Study Drug Discontinuation Through Week 52	Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. A Serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.	Baseline up to Week 52
Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) From Baseline Through Week 52	Any untoward medical occurrence in a participants who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to end of treatment at Week 52). Any TEAE included participants with both serious and non-serious AEs. Skin infection TEAEs were identified based on blinded adjudication of all reported TEAEs under the 2 primary System Organ Classes (SOC): SOC = "Infection and Infestations" or SOC = "Skin and Subcutaneous Tissue Disorders". Blinded adjudication was performed and finalized by the study medical monitor before database lock.	Baseline up to Week 52
Number of Skin Infection TEAEs (Excluding Herpetic Infections) From Baseline Through Week 52	Any untoward medical occurrence in a participant who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to end of treatment at Week 52). Any TEAE included participants with both serious and non-serious AEs. Skin infection TEAEs were identified based on blinded adjudication of all reported TEAEs under the 2 primary System Organ Classes (SOC): SOC = "Infection and Infestations" or SOC = "Skin and Subcutaneous Tissue Disorders". Blinded adjudication was performed and finalized by the study medical monitor before database lock.	Baseline up to Week 52
Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Requiring Systemic Treatment From Baseline Through Week 52	Any untoward medical occurrence in a participant who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to end of treatment at Week 52). Any TEAE included participants with both serious and non-serious AEs. Skin infection TEAEs were identified based on blinded adjudication of all reported TEAEs under the 2 primary System Organ Classes (SOC): SOC = "Infection and Infestations" or SOC = "Skin and Subcutaneous Tissue Disorders". Blinded adjudication was performed and finalized by the study medical monitor before database lock.	Baseline up to Week 52
Number of Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Requiring Systemic Treatment From Baseline Through Week 52	Any untoward medical occurrence in a participant who received IMP was considered an AE without regard to possibility of causal relationship with this treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to end of treatment at Week 52). Any TEAE included participants with both serious and non-serious AEs. Skin infection TEAEs were identified based on blinded adjudication of all reported TEAEs under the 2 primary System Organ Classes (SOC): SOC = "Infection and Infestations" or SOC = "Skin and Subcutaneous Tissue Disorders". Blinded adjudication was performed and finalized by the study medical monitor before database lock.	Baseline up to Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Sinonasal Outcome Test (SNOT-22) Score to Week 16	The SNOT 22 was a validated measure of health related quality of life in sinonasal disease. It was a 22 item questionnaire with each item assigned a score ranging from 0-5. The total score may range from 0 (no disease) -110 (worst disease) (lower scores represent better health related quality of life). The SNOT-22 was administered only to participants with chronic inflammatory conditions of the nasal mucosa and/or paranasal sinuses.	Baseline to Week 16
Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score to Week 16	ACQ-5 questionnaire was a validated questionnaire comprising of 5 questions for asthma symptoms: woken at night by symptoms, wake in the mornings with symptoms, limitation of daily activities, shortness of breath, and wheeze. Participants were asked to rate their asthma symptoms during the previous week on a 7-point scale as 0=no impairment, 6=maximum impairment. ACQ-5 score was the mean of the 5 questions and range between 0 (totally controlled) and 6 (severely uncontrolled) (a higher score indicated lower asthma control). The ACQ-5 questionnaire was administered only to the participants with a medical history of asthma.	Baseline to Week 16

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi

Publications and helpful links

General Publications

• Wechsler ME, Klion AD, Paggiaro P, Nair P, Staumont-Salle D, Radwan A, Johnson RR, Kapoor U, Khokhar FA, Daizadeh N, Chen Z, Laws E, Ortiz B, Jacob-Nara JA, Mannent LP, Rowe PJ, Deniz Y. Effect of Dupilumab on Blood Eosinophil Counts in Patients With Asthma, Chronic Rhinosinusitis With Nasal Polyps, Atopic Dermatitis, or Eosinophilic Esophagitis. J Allergy Clin Immunol Pract. 2022 Oct;10(10):2695-2709. doi: 10.1016/j.jaip.2022.05.019. Epub 2022 May 28.
• Hamilton JD, Harel S, Swanson BN, Brian W, Chen Z, Rice MS, Amin N, Ardeleanu M, Radin A, Shumel B, Ruddy M, Patel N, Pirozzi G, Mannent L, Graham NMH. Dupilumab suppresses type 2 inflammatory biomarkers across multiple atopic, allergic diseases. Clin Exp Allergy. 2021 Jul;51(7):915-931. doi: 10.1111/cea.13954. Epub 2021 Jun 26.
• Griffiths C, de Bruin-Weller M, Deleuran M, Fargnoli MC, Staumont-Salle D, Hong CH, Sanchez-Carazo J, Foley P, Seo SJ, Msihid J, Chen Z, Cyr SL, Rossi AB. Dupilumab in Adults with Moderate-to-Severe Atopic Dermatitis and Prior Use of Systemic Non-Steroidal Immunosuppressants: Analysis of Four Phase 3 Trials. Dermatol Ther (Heidelb). 2021 Aug;11(4):1357-1372. doi: 10.1007/s13555-021-00558-0. Epub 2021 Jun 18.
• Boguniewicz M, Beck LA, Sher L, Guttman-Yassky E, Thaci D, Blauvelt A, Worm M, Corren J, Soong W, Lio P, Rossi AB, Lu Y, Chao J, Eckert L, Gadkari A, Hultsch T, Ruddy M, Mannent LP, Graham NMH, Pirozzi G, Chen Z, Ardeleanu M. Dupilumab Improves Asthma and Sinonasal Outcomes in Adults with Moderate to Severe Atopic Dermatitis. J Allergy Clin Immunol Pract. 2021 Mar;9(3):1212-1223.e6. doi: 10.1016/j.jaip.2020.12.059. Epub 2021 Jan 13.
• Silverberg JI, Simpson EL, Guttman-Yassky E, Cork MJ, de Bruin-Weller M, Yosipovitch G, Eckert L, Chen Z, Ardeleanu M, Shumel B, Hultsch T, Rossi AB, Hamilton JD, Orengo JM, Ruddy M, Graham NMH, Pirozzi G, Gadkari A. Dupilumab Significantly Modulates Pain and Discomfort in Patients With Atopic Dermatitis: A Post Hoc Analysis of 5 Randomized Clinical Trials. Dermatitis. 2021 Oct 1;32(1S):S81-S91. doi: 10.1097/DER.0000000000000698.
• Alexis AF, Rendon M, Silverberg JI, Pariser DM, Lockshin B, Griffiths CE, Weisman J, Wollenberg A, Chen Z, Davis JD, Li M, Eckert L, Gadkari A, Shumel B, Rossi AB, Graham NM, Ardeleanu M. Efficacy of Dupilumab in Different Racial Subgroups of Adults With Moderate-to-Severe Atopic Dermatitis in Three Randomized, Placebo-Controlled Phase 3 Trials. J Drugs Dermatol. 2019 Aug 1;18(8):804-813.
• Wollenberg A, Beck LA, Blauvelt A, Simpson EL, Chen Z, Chen Q, Shumel B, Khokhar FA, Hultsch T, Rizova E, Rossi AB, Graham NMH, Pirozzi G, Lu Y, Ardeleanu M. Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS). Br J Dermatol. 2020 May;182(5):1120-1135. doi: 10.1111/bjd.18434. Epub 2019 Dec 1.
• Blauvelt A, de Bruin-Weller M, Simpson EL, Chen Z, Ardeleanu M, Rossi AB. Consistency of Response to Dupilumab in Adults with Moderate-to-Severe Atopic Dermatitis Over 1 Year. Dermatol Ther (Heidelb). 2022 Jan;12(1):9-13. doi: 10.1007/s13555-021-00657-y. Epub 2022 Jan 7.
• Blauvelt A, de Bruin-Weller M, Simpson EL, Chen Z, Zhang A, Shumel B. Dupilumab with Topical Corticosteroids Provides Rapid and Sustained Improvement in Adults with Moderate-to-Severe Atopic Dermatitis Across Anatomic Regions Over 52 Weeks. Dermatol Ther (Heidelb). 2022 Jan;12(1):223-231. doi: 10.1007/s13555-021-00638-1. Epub 2021 Nov 22.
• Wu JJ, Spelman L, Tan JL, Etoh T, Zhang H, Shumel B, Rossi AB. Dupilumab Maintains Long-Term Disease Control in Adults with Moderate-to-Severe Atopic Dermatitis as Measured by Well-Controlled Weeks: Results From the LIBERTY AD CHRONOS Clinical Trial. Dermatol Ther (Heidelb). 2021 Apr;11(2):327-330. doi: 10.1007/s13555-021-00487-y. Epub 2021 Jan 28. No abstract available.
• Weyne J, Blauvelt A, de Bruin-Weller M, Prens E, Asbell P, Sierka D, Chen Z, Shumel B. Patient-Reported Ocular Disorders and Symptoms in Adults with Moderate-to-Severe Atopic Dermatitis: Screening and Baseline Survey Data from a Clinical Trial. Dermatol Ther (Heidelb). 2020 Dec;10(6):1415-1421. doi: 10.1007/s13555-020-00456-x. Epub 2020 Oct 12.
• Katoh N, Kataoka Y, Saeki H, Hide M, Kabashima K, Etoh T, Igarashi A, Imafuku S, Kawashima M, Ohtsuki M, Fujita H, Arima K, Takagi H, Chen Z, Shumel B, Ardeleanu M. Efficacy and safety of dupilumab in Japanese adults with moderate-to-severe atopic dermatitis: a subanalysis of three clinical trials. Br J Dermatol. 2020 Jul;183(1):39-51. doi: 10.1111/bjd.18565. Epub 2019 Nov 28.
• Blauvelt A, de Bruin-Weller M, Gooderham M, Cather JC, Weisman J, Pariser D, Simpson EL, Papp KA, Hong HC, Rubel D, Foley P, Prens E, Griffiths CEM, Etoh T, Pinto PH, Pujol RM, Szepietowski JC, Ettler K, Kemeny L, Zhu X, Akinlade B, Hultsch T, Mastey V, Gadkari A, Eckert L, Amin N, Graham NMH, Pirozzi G, Stahl N, Yancopoulos GD, Shumel B. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet. 2017 Jun 10;389(10086):2287-2303. doi: 10.1016/S0140-6736(17)31191-1. Epub 2017 May 4.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: October 6, 2014
• First Submitted That Met QC Criteria: October 6, 2014
• First Posted (Estimate): October 9, 2014

Study Record Updates

• Last Update Posted (Actual): October 17, 2017
• Last Update Submitted That Met QC Criteria: October 12, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: R668-AD-1224