Clinical trial NCT02260986: Study to Assess the Efficacy and Long-term Safety of Dupilumab (REGN668/SAR231893) in Adult Participants With Moderate-to-Severe Atopic Dermatitis
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atopic Dermatitis
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2014-10-09
Enrollment: 740
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of ≥2 Points at Week 16
timeFrame: Baseline to Week 16
Secondary outcomes:
measure: Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 16
timeFrame: Baseline to Week 16
measure: 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
timeFrame: Baseline to Week 16
measure: 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
timeFrame: Baseline to Week 16
measure: Percentage of Participants With Investigator's Global Assessment (IGA) Score of "0" or "1" and Reduction From Baseline of ≥2 Points at Week 52
timeFrame: Baseline to Week 52
measure: Percentage of Participants With Eczema Area and Severity Index-75 (EASI-75) (≥75% Improvement From Baseline) at Week 52
timeFrame: Baseline to Week 52
measure: Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16
timeFrame: Baseline to Week 16
measure: 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
timeFrame: Baseline to Week 52
measure: 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
timeFrame: Baseline to Week 52
measure: 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
timeFrame: Baseline to Week 24
measure: 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
timeFrame: Baseline to Week 4
measure: 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
timeFrame: Baseline to Week 2
measure: Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 16
timeFrame: Baseline to Week 16
measure: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 16
timeFrame: Baseline to Week 16
measure: Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis to Week 16
timeFrame: Baseline to Week 16
measure: Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 16
timeFrame: Baseline to Week 16
measure: Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 16
timeFrame: Baseline to Week 16
measure: Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 16
timeFrame: Baseline to Week 16
measure: Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 16
timeFrame: Baseline to Week 16
measure: Percent Change From Baseline in Total Global Individual Signs Score (GISS) to Week 16
timeFrame: Baseline to Week 16
measure: Proportion of Topical Atopic Dermatitis Medication-Free Days Through Week 52
timeFrame: Baseline to Week 52
measure: Percent Change From Baseline in Weekly Average of Peak Daily Pruritus Numerical Rating Scale (NRS) Score to Week 2
timeFrame: Baseline to Week 2
measure: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score to Week 52
timeFrame: Baseline to Week 52
measure: Change From Baseline in Percent Body Surface Area (BSA) Affected by Atopic Dermatitis to Week 52
timeFrame: Baseline to Week 52
measure: Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Score to Week 52
timeFrame: Baseline to Week 52
measure: Percent Change From Baseline in Global Individual Signs Score (GISS) to Week 52
timeFrame: Baseline to Week 52
measure: Change From Baseline in Dermatology Life Quality Index (DLQI) to Week 52
timeFrame: Baseline to Week 52
measure: Change From Baseline in Patient Oriented Eczema Measure (POEM) to Week 52
timeFrame: Baseline to Week 52
measure: Change From Baseline in Hospital Anxiety Depression Scale (HADS) to Week 52
timeFrame: Baseline to Week 52
measure: Number of Flares Through Week 52
timeFrame: Baseline up to Week 52
measure: Number of Serious Treatment Emergent Adverse Events (TEAEs) Leading to Study Drug Discontinuation Through Week 52
timeFrame: Baseline up to Week 52
measure: Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) From Baseline Through Week 52
timeFrame: Baseline up to Week 52
measure: Number of Skin Infection TEAEs (Excluding Herpetic Infections) From Baseline Through Week 52
timeFrame: Baseline up to Week 52
measure: Percentage of Participants With Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Requiring Systemic Treatment From Baseline Through Week 52
timeFrame: Baseline up to Week 52
measure: Number of Skin Infection Treatment Emergent Adverse Events (TEAEs) (Excluding Herpetic Infections) Requiring Systemic Treatment From Baseline Through Week 52
timeFrame: Baseline up to Week 52
Other outcomes:
measure: Change From Baseline in Sinonasal Outcome Test (SNOT-22) Score to Week 16
timeFrame: Baseline to Week 16
measure: Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score to Week 16
timeFrame: Baseline to Week 16
Locations:
city: Phoenix
country: United States
state: Arizona
city: Hot Springs
country: United States
state: Arkansas
city: Little Rock
country: United States
state: Arkansas
city: Encinitas
country: United States
state: California
city: Oceanside
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state: California
city: Palmdale
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state: California
city: San Diego
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state: California
city: New Haven
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state: Connecticut
city: Trumbull
country: United States
state: Connecticut
city: Edgewater
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state: Florida
city: Lake Worth
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state: Florida
city: Miami Lakes
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state: Florida
city: Orlando
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state: Florida
city: Tampa
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state: Florida
city: Alpharetta
country: United States
state: Georgia
city: Columbus
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state: Georgia
city: Savannah
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state: Georgia
city: West Dundee
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state: Illinois
city: Carmel
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state: Indiana
city: New Albany
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state: Indiana
city: Rockville
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state: Maryland
city: Ann Arbor
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state: Michigan
city: Bay City
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state: Michigan
city: Edina
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state: Minnesota
city: Fridley
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state: Minnesota
city: Saint Louis
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state: Missouri
city: Omaha
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state: Nebraska
city: Henderson
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state: Nevada
city: Verona
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state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Corning
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state: New York
city: New York
country: United States
state: New York
city: Smithtown
country: United States
state: New York
city: Stony Brook
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Norman
country: United States
state: Oklahoma
city: Oklahoma City
country: United States
state: Oklahoma
city: Lake Oswego
country: United States
state: Oregon
city: Portland
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state: Oregon
city: Exton
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state: Pennsylvania
city: Hazleton
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state: Pennsylvania
city: Philadelphia
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state: Pennsylvania
city: Austin
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state: Texas
city: Dallas
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state: Texas
city: West Jordan
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state: Utah
city: South Burlington
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state: Vermont
city: Henrico
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Spokane
country: United States
state: Washington
city: Phillip
country: Australia
state: Australian Capital Territory
city: Kogarah
country: Australia
state: New South Wales
city: Benowa
country: Australia
state: Queensland
city: Dulwich
country: Australia
state: Queensland
city: Hectorville
country: Australia
state: South Australia
city: Carlton
country: Australia
state: Victoria
city: Surrey
country: Canada
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
city: Ajax
country: Canada
state: Ontario
city: Barrie
country: Canada
state: Ontario
city: Hamilton
country: Canada
state: Ontario
city: Markham
country: Canada
state: Ontario
city: North Bay
country: Canada
state: Ontario
city: Oakville
country: Canada
state: Ontario
city: Ottawa
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state: Ontario
city: Peterborough
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state: Ontario
city: Richmond Hill
country: Canada
state: Ontario
city: Toronto
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state: Ontario
city: Waterloo
country: Canada
state: Ontario
city: Windsor
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state: Ontario
city: Drummondville
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Hradec Kralove
country: Czechia
city: Nachod
country: Czechia
city: Praha 10
country: Czechia
city: Praha 5
country: Czechia
city: Svitavy
country: Czechia
city: Usti nad Labem
country: Czechia
city: Oroshaza
country: Hungary
state: Békés
city: Szolnok
country: Hungary
state: Jász-Nagykun-Szolnok
city: Veszprem
country: Hungary
state: Veszprém
city: Budapest
country: Hungary
city: Ancona
country: Italy
city: Bologna
country: Italy
city: Brescia
country: Italy
city: Novara
country: Italy
city: Pavia
country: Italy
city: Perugia
country: Italy
city: Roma
country: Italy
city: Kitakyushu
country: Japan
state: Fukuoka
city: Amagasaki
country: Japan
state: Hyôgo
city: Yokohama
country: Japan
state: Kanagawa
city: Kamimashiki-gun
country: Japan
state: Kumamoto
city: Saitama-shi
country: Japan
state: Saitama
city: Yaizu
country: Japan
state: Shizuoka
city: Koto-ku
country: Japan
state: Tokyo
city: Setagaya-ku
country: Japan
state: Tokyo
city: Adachi-ku
country: Japan
state: Tôkyô
city: Chiyoda-ku
country: Japan
state: Tôkyô
city: Nakano-ku
country: Japan
state: Tôkyô
city: Nerima-ku
country: Japan
state: Tôkyô
city: Shibuya-ku
country: Japan
state: Tôkyô
city: Shinagawa-ku
country: Japan
state: Tôkyô
city: Shinjuku-ku
country: Japan
state: Tôkyô
city: Suginami-ku
country: Japan
state: Tôkyô
city: Fukuoka
country: Japan
city: Bucheon-si
country: Korea, Republic of
state: Gyeonggido
city: Suwon
country: Korea, Republic of
state: Gyeonggido
city: Seoul
country: Korea, Republic of
state: Seoul Teugbyeolsi
city: Seodaemun-gu
country: Korea, Republic of
city: Uijeongbu-si
country: Korea, Republic of
city: Breda
country: Netherlands
state: Noord-Brabant
city: Amsterdam
country: Netherlands
state: Noord-Holland
city: Rotterdam
country: Netherlands
state: Zuid-Holland
city: Groningen
country: Netherlands
city: Utrecht
country: Netherlands
city: Dunedin
country: New Zealand
state: South Island
city: Auckland
country: New Zealand
city: Wroclaw
country: Poland
state: Dolnośląskie
city: Lublin
country: Poland
state: Lubelskie
city: Warszawa
country: Poland
state: Mazowieckie
city: Krakow
country: Poland
state: Małopolskie
city: Strzelce Opolskie
country: Poland
state: Opolskie
city: Iwonicz Zdroj
country: Poland
state: Podkarpackie
city: Bialystok
country: Poland
state: Podlaskie
city: Gdansk
country: Poland
state: Pomorskie
city: Poznan
country: Poland
state: Wielkopolskie
city: Szczecin
country: Poland
state: Zachodniopomorskie
city: Gdynia
country: Poland
city: Łódź
country: Poland
state: Łódzkie
city: Katowice
country: Poland
state: Śląskie
city: Skarzysko-Kamienna
country: Poland
state: Świętokrzyskie
city: Brasov
country: Romania
state: Braşov
city: Bucuresti
country: Romania
state: Bucureşti
city: Cluj-Napoca
country: Romania
state: Cluj
city: Craiova
country: Romania
state: Dolj
city: Targu Mures
country: Romania
state: Mureş
city: Barcelona
country: Spain
state: Cataluña
city: Alicante
country: Spain
city: Madrid
country: Spain
city: Dundee
country: United Kingdom
state: Angus
city: Edgbaston
country: United Kingdom
state: Birmingham
city: Glasgow
country: United Kingdom
state: Glasgow City
city: Sidcup
country: United Kingdom
state: Kent
city: Northwood
country: United Kingdom
state: Middlesex
city: Liverpool
country: United Kingdom
city: Manchester
country: United Kingdom
city: Reading
country: United Kingdom
city: Salford
country: United Kingdom
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: 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.
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citation: 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.
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citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.