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

NCT ID: NCT02260986

Last Updated: 2017-10-17

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

740 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-09-30

Study Completion Date

2016-10-31

Brief Summary

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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.

Detailed Description

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Conditions

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Atopic Dermatitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Placebo (for Dupilumab)

Intervention Type DRUG

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

Topical Corticosteroid (TCS)

Intervention Type OTHER

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.

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.

Group Type EXPERIMENTAL

Dupilumab

Intervention Type DRUG

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

Placebo (for Dupilumab)

Intervention Type DRUG

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

Topical Corticosteroid (TCS)

Intervention Type OTHER

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.

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.

Group Type EXPERIMENTAL

Dupilumab

Intervention Type DRUG

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

Topical Corticosteroid (TCS)

Intervention Type OTHER

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.

Interventions

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Dupilumab

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

Intervention Type DRUG

Placebo (for Dupilumab)

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

Intervention Type DRUG

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 Type OTHER

Other Intervention Names

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REGN668 SAR231893 Dupixent

Eligibility Criteria

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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).

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanofi

INDUSTRY

Sponsor Role collaborator

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trial Management

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

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Phoenix, Arizona, United States

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Hot Springs, Arkansas, United States

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Little Rock, Arkansas, United States

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Encinitas, California, United States

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Oceanside, California, United States

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Palmdale, California, United States

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San Diego, California, United States

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New Haven, Connecticut, United States

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Trumbull, Connecticut, United States

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Edgewater, Florida, United States

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Lake Worth, Florida, United States

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Miami Lakes, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Alpharetta, Georgia, United States

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Columbus, Georgia, United States

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Savannah, Georgia, United States

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West Dundee, Illinois, United States

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Carmel, Indiana, United States

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New Albany, Indiana, United States

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Rockville, Maryland, United States

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Ann Arbor, Michigan, United States

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Bay City, Michigan, United States

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Edina, Minnesota, United States

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Fridley, Minnesota, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Henderson, Nevada, United States

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Verona, New Jersey, United States

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Albuquerque, New Mexico, United States

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Corning, New York, United States

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New York, New York, United States

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Smithtown, New York, United States

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Stony Brook, New York, United States

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Cincinnati, Ohio, United States

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Norman, Oklahoma, United States

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Oklahoma City, Oklahoma, United States

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Lake Oswego, Oregon, United States

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Portland, Oregon, United States

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Exton, Pennsylvania, United States

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Hazleton, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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West Jordan, Utah, United States

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South Burlington, Vermont, United States

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Henrico, Virginia, United States

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Norfolk, Virginia, United States

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Richmond, Virginia, United States

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Spokane, Washington, United States

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Phillip, Australian Capital Territory, Australia

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Kogarah, New South Wales, Australia

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Benowa, Queensland, Australia

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Dulwich, Queensland, Australia

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Hectorville, South Australia, Australia

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Carlton, Victoria, Australia

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Surrey, British Columbia, Canada

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Vancouver, British Columbia, Canada

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Ajax, Ontario, Canada

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Barrie, Ontario, Canada

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Hamilton, Ontario, Canada

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Markham, Ontario, Canada

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North Bay, Ontario, Canada

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Oakville, Ontario, Canada

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Ottawa, Ontario, Canada

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Peterborough, Ontario, Canada

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Richmond Hill, Ontario, Canada

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Toronto, Ontario, Canada

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Waterloo, Ontario, Canada

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Windsor, Ontario, Canada

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Drummondville, Quebec, Canada

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Québec, , Canada

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Hradec Králové, , Czechia

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Náchod, , Czechia

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Prague, , Czechia

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Svitavy, , Czechia

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Ústí nad Labem, , Czechia

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Orosháza, Bekes County, Hungary

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Szolnok, Jász-Nagykun-Szolnok, Hungary

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Veszprém, Veszprém megye, Hungary

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Budapest, , Hungary

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Ancona, , Italy

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Bologna, , Italy

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Brescia, , Italy

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Novara, , Italy

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Pavia, , Italy

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Perugia, , Italy

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Roma, , Italy

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Kitakyushu, Fukuoka, Japan

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Amagasaki, Hyôgo, Japan

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Yokohama, Kanagawa, Japan

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Kamimashiki-gun, Kumamoto, Japan

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Saitama-shi, Saitama, Japan

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Yaizu, Shizuoka, Japan

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Koto-ku, Tokyo, Japan

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Setagaya-ku, Tokyo, Japan

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Adachi-ku, Tôkyô, Japan

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Chiyoda-ku, Tôkyô, Japan

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Nakano, Tôkyô, Japan

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Nerima-ku, Tôkyô, Japan

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Shibuya-ku, Tôkyô, Japan

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Shinagawa-ku, Tôkyô, Japan

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Shinjuku-ku, Tôkyô, Japan

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Suginami-ku, Tôkyô, Japan

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Fukuoka, , Japan

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Breda, North Brabant, Netherlands

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Amsterdam, North Holland, Netherlands

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Rotterdam, South Holland, Netherlands

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Groningen, , Netherlands

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Utrecht, , Netherlands

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Dunedin, South Island, New Zealand

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Auckland, , New Zealand

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Poznan, Greater Poland Voivodeship, Poland

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Krakow, Lesser Poland Voivodeship, Poland

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Wroclaw, Lower Silesian Voivodeship, Poland

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Lublin, Lublin Voivodeship, Poland

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Warsaw, Masovian Voivodeship, Poland

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Strzelce Opolskie, Opole Voivodeship, Poland

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Iwonicz-Zdrój, Podkarpackie Voivodeship, Poland

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Bialystok, Podlaskie Voivodeship, Poland

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Gdansk, Pomeranian Voivodeship, Poland

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Katowice, Silesian Voivodeship, Poland

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Szczecin, West Pomeranian Voivodeship, Poland

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Gdynia, , Poland

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Lodz, Łódź Voivodeship, Poland

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Skarżysko-Kamienna, Świętokrzyskie Voivodeship, Poland

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Brasov, Brașov County, Romania

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Bucharest, București, Romania

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Cluj-Napoca, Cluj, Romania

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Craiova, Dolj, Romania

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Târgu Mureş, Mureș County, Romania

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Bucheon-si, Gyeonggido, South Korea

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Suwon, Gyeonggido, South Korea

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Seoul, Seoul Teugbyeolsi, South Korea

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Seodaemun-gu, , South Korea

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Uijeongbu-si, , South Korea

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Barcelona, Catalonia, Spain

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Alicante, , Spain

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Madrid, , Spain

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Dundee, Angus, United Kingdom

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Edgbaston, Birmingham, United Kingdom

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Glasgow, Glasgow City, United Kingdom

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Sidcup, Kent, United Kingdom

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Northwood, Middlesex, United Kingdom

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Liverpool, , United Kingdom

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Manchester, , United Kingdom

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Reading, , United Kingdom

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Salford, , United Kingdom

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Countries

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France Germany Latvia Russia Taiwan United States Australia Canada Czechia Hungary Italy Japan Netherlands New Zealand Poland Romania South Korea Spain United Kingdom

References

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Wiseman M, Benvenuto M, Stromkjaer L, Paludan-Muller A, Ryttig L, Petersen AS, Wollenberg A. Cost-Per-Responder Analysis for Tralokinumab and Dupilumab in Combination with Topical Corticosteroids in Patients with Moderate-To-Severe Atopic Dermatitis. Dermatol Ther (Heidelb). 2025 Oct 16. doi: 10.1007/s13555-025-01565-1. Online ahead of print.

Reference Type DERIVED
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Langley RG, Gherardi G, Coleman A, Ardeleanu M, Rodriguez-Marco A, Levy S, Bansal A, Chen Z, Rossi AB, Shumel B, Khokhar FA. The Safety Data of Dupilumab for the Treatment of Moderate-to-Severe Atopic Dermatitis in Infants, Children, Adolescents, and Adults. Am J Clin Dermatol. 2025 Sep 24. doi: 10.1007/s40257-025-00952-w. Online ahead of print.

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Stander S, Yosipovitch G, Kim BS, Steinhoff M, Armstrong A, Legat FJ, Kabashima K, Nakahara T, Igarashi A, Praestgaard AH, Nguyen TV, Bastian M. Optimal Itch Response in Adults Treated with Dupilumab for Moderate-to-Severe Atopic Dermatitis. Dermatol Ther (Heidelb). 2025 Sep 19. doi: 10.1007/s13555-025-01519-7. Online ahead of print.

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PMID: 40971025 (View on PubMed)

Stander S, Yosipovitch G, Simpson EL, Kim BS, Kabashima K, Thaci D, Metz M, Chen Z, Hagen S, Bastian M. Onset and Long-Term Maintenance of Optimal Itch Response in Adult Patients with Moderate-to-Severe Atopic Dermatitis Treated with Dupilumab: Post Hoc Analysis from Two Phase 3 Trials. Adv Ther. 2025 Apr;42(4):1800-1810. doi: 10.1007/s12325-025-03124-8. Epub 2025 Feb 19.

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Kamal MA, Kosloski MP, Lai CH, Partridge MA, Rajadhyaksha M, Kanamaluru V, Bansal A, Shabbir A, Shumel B, Ardeleanu M, Richards SM, Yan H, Xu CR, Rodriguez-Marco A, Xiao J, Khokhar FA, Gherardi G, Babilonia E, Maloney J, Mortensen E, Akinlade B, Braunstein N, Stahl N, Torri A, Davis JD, DiCioccio AT. Immunogenicity of dupilumab in adult and pediatric patients with atopic dermatitis. Front Immunol. 2024 Nov 11;15:1466372. doi: 10.3389/fimmu.2024.1466372. eCollection 2024.

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Silverberg JI, Lynde CW, Abuabara K, Patruno C, de Benedetto A, Zhang H, Thomas RB, Bego-Le-Bagousse G, Khokhar FA, Vakil J, Marco AR, Levit NA. Efficacy and Safety of Dupilumab Maintained in Adults >/= 60 Years of Age with Moderate-to-Severe Atopic Dermatitis: Analysis of Pooled Data from Four Randomized Clinical Trials. Am J Clin Dermatol. 2023 May;24(3):469-483. doi: 10.1007/s40257-022-00754-4. Epub 2023 Feb 20.

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PMID: 36808602 (View on PubMed)

Paller AS, Silverberg JI, Cork MJ, Guttman-Yassky E, Lockshin B, Irvine AD, Kim MB, Kabashima K, Chen Z, Lu Y, Bansal A, Rossi AB, Shabbir A. Efficacy and Safety of Dupilumab in Patients With Erythrodermic Atopic Dermatitis: A Post Hoc Analysis of 6 Randomized Clinical Trials. JAMA Dermatol. 2023 Mar 1;159(3):255-266. doi: 10.1001/jamadermatol.2022.6192.

Reference Type DERIVED
PMID: 36723913 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35636689 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34994968 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34806137 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34142350 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34037993 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33511576 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33453450 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33165005 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33047298 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31564057 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31424712 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31407311 (View on PubMed)

Eichenfield LF, Bieber T, Beck LA, Simpson EL, Thaci D, de Bruin-Weller M, Deleuran M, Silverberg JI, Ferrandiz C, Folster-Holst R, Chen Z, Graham NMH, Pirozzi G, Akinlade B, Yancopoulos GD, Ardeleanu M. Infections in Dupilumab Clinical Trials in Atopic Dermatitis: A Comprehensive Pooled Analysis. Am J Clin Dermatol. 2019 Jun;20(3):443-456. doi: 10.1007/s40257-019-00445-7.

Reference Type DERIVED
PMID: 31066001 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28478972 (View on PubMed)

Other Identifiers

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R668-AD-1224

Identifier Type: -

Identifier Source: org_study_id