Clinical trial NCT03738397: A Study to Compare Safety and Efficacy of Upadacitinib to Dupilumab in Adult Participants With Moderate to Severe Atopic Dermatitis
Official title: A Phase 3b Multicenter, Randomized, Double-Blind, Double-Dummy, Active Controlled Study Comparing the Safety and Efficacy of Upadacitinib to Dupilumab in Adult Subjects With Moderate to Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atopic Dermatitis
Keywords: Upadacitinib
ABT-494
Dupilumab
Atopic Dermatitis
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2018-11-13
Enrollment: 673
Sex: ALL
Minimum age (years): 18
Maximum age (years): 76
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate upadacitinib compared to dupilumab (Dupixent®) in adults with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.

Detailed description: The study is comprised of a 35-day screening period, a 24-week double-blinded treatment period, and a follow-up visit 12 weeks after the last dose. Participants who complete Week 24 have the option to enroll into an open-label study (Study M19-850; NCT04195698) of upadacitinib 30 mg once daily and receive treatment with upadacitinib for an additional 52 weeks.

Participants who meet eligibility criteria will be randomized in a 1:1 ratio to receive either upadacitinib or dupilumab. Randomization will be stratified by Baseline disease severity (Validated Investigator Global Assessment scale for Atopic Dermatitis \[vIGA-AD\] score of moderate \[3\] versus severe \[4\]) and age (\<40, ≥ 40 to \< 65, ≥ 65 years).

Eligibility criteria: Inclusion Criteria:

* Participant has active moderate to severe atopic dermatitis (AD) defined by Eczema Area and Severity Index (EASI) ≥ 16, Investigator's Global Assessment (IGA) ≥ 3, ≥ 10% body surface area (BSA) of AD involvement at the Screening and Baseline Visits, and Baseline weekly average of daily Worst Pruritus NRS ≥ 4.
* Participant is a candidate for systemic therapy or have recently required systemic therapy for AD.

Exclusion Criteria:

* Participant has prior exposure to Janus Kinase (JAK) inhibitor.
* Participant has prior exposure to dupilumab.
* Participant is unable or unwilling to discontinue current AD treatments prior to the study.
* Participant has requirement of prohibited medications during the study.
* Participant has other active skin diseases or skin infections requiring systemic treatment or would interfere with appropriate assessment of AD lesions.
* Female participant who is pregnant, breastfeeding, or considering pregnancy during the study.

Primary outcomes:
measure: Percentage of Participants Achieving a 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75) at Week 16
timeFrame: Baseline and Week 16
Secondary outcomes:
measure: Percent Change From Baseline in Worst Pruritus Numerical Rating Scale (NRS) Score at Week 16
timeFrame: Baseline (Week 0) to Week 16
measure: Percentage of Participants Achieving a 100% Reduction From Baseline in EASI Score (EASI 100) at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants Achieving a 90% Reduction From Baseline in EASI Score (EASI 90) at Week 16
timeFrame: Baseline and Week 16
measure: Percent Change From Baseline in Worst Pruritus Numerical Rating Scale (NRS) Score at Week 4
timeFrame: Baseline (Week 0) to Week 4
measure: Percentage of Participants Achieving a 75% Reduction From Baseline in EASI Score at Week 2
timeFrame: Baseline and Week 2
measure: Percent Change From Baseline in Worst Pruritus Numerical Rating Scale (NRS) Score at Week 1
timeFrame: Baseline (Week 0) to Week 1
measure: Percentage of Participants Achieving a Reduction of ≥ 4 Points From Baseline in Worst Pruritus NRS at Week 16
timeFrame: Baseline and Week 16
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Research Center AL /ID# 210277
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences /ID# 211688
state: Arkansas
city: Fountain Valley
country: United States
facility: Tien Q Nguyen MD, Inc /ID# 208934
state: California
city: Fresno
country: United States
facility: UCSF Fresno /ID# 213253
state: California
city: Los Angeles
country: United States
facility: Jonathan Corren, MD. INC /ID# 208987
state: California
city: Los Angeles
country: United States
facility: California Allergy and Asthma Medical Group /ID# 213680
state: California
city: Los Angeles
country: United States
facility: Dermatology Research Associates /ID# 209097
state: California
city: Los Angeles
country: United States
facility: Los Angelos Cataract Center /ID# 208524
state: California
city: Newport Beach
country: United States
facility: Dermatology Clinical Trials /ID# 214622
state: California
city: Sacramento
country: United States
facility: UC Davis Health /ID# 209285
state: California
city: San Diego
country: United States
facility: Ucsd /Id# 208990
state: California
city: Santa Monica
country: United States
facility: Clinical Science Institute /ID# 211022
state: California
city: Hialeah
country: United States
facility: The Community Research of South Florida /ID# 211145
state: Florida
city: Miami
country: United States
facility: Miami Dermatology and Laser Institute /ID# 212938
state: Florida
city: Miami
country: United States
facility: Florida International Rsrch cr /ID# 211562
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research /ID# 211994
state: Florida
city: Saint Petersburg
country: United States
facility: GCP Research /ID# 216020
state: Florida
city: Tampa
country: United States
facility: Clinical Research Trials of Florida, Inc. /ID# 210751
state: Florida
city: West Palm Beach
country: United States
facility: Integrated Clinical Research LLC /ID# 208831
state: Florida
city: Albany
country: United States
facility: Georgia Pollens Clinical Research Centers, Inc /ID# 211092
state: Georgia
city: Savannah
country: United States
facility: Meridian Clinical Research Dermatology /ID# 213251
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine /ID# 208680
state: Illinois
city: Chicago
country: United States
facility: Medical Dermatology Associates of Chicago /ID# 210265
state: Illinois
city: Normal
country: United States
facility: Sneeze, Wheeze, & Itch Associates, LLC /ID# 212058
state: Illinois
city: Indianapolis
country: United States
facility: Dawes Fretzin, LLC /ID# 209187
state: Indiana
city: Quincy
country: United States
facility: Beacon Clinical Research, LLC /ID# 209280
state: Massachusetts
city: Clarkston
country: United States
facility: Clarkston Skin Research /ID# 208739
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System /ID# 208741
state: Michigan
city: Minneapolis
country: United States
facility: Clinical Research Institute, Inc /ID# 210852
state: Minnesota
city: Lincoln
country: United States
facility: Allergy, Asthma & Immunology Associates, PC /ID# 213481
state: Nebraska
city: Omaha
country: United States
facility: Skin Specialists, PC /ID# 208843
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center /ID# 213727
state: New Hampshire
city: Bronx
country: United States
facility: Montefiore Medical Center /ID# 209647
state: New York
city: Kew Gardens
country: United States
facility: Forest Hills Dermatology Group /ID# 209249
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Univ HS /ID# 208892
state: North Carolina
city: Cleveland
country: United States
facility: Univ Hosp Cleveland /ID# 208852
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University /ID# 209254
state: Ohio
city: Tulsa
country: United States
facility: Southside Dermatology /ID# 212004
state: Oklahoma
city: Portland
country: United States
facility: Oregon Medical Res Center PC /ID# 208807
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University /ID# 208809
state: Oregon
city: Charleston
country: United States
facility: Medical University of South Carolina /ID# 211054
state: South Carolina
city: Jackson
country: United States
facility: Clinical Research Solutions, LLC /ID# 212542
state: Tennessee
city: Austin
country: United States
facility: Orion Clinical Research /ID# 208765
state: Texas
city: Bryan
country: United States
facility: DiscoveResearch, Inc. /ID# 213171
state: Texas
city: Fort Worth
country: United States
facility: Epiphany Dermatology - Fort Worth /ID# 211187
state: Texas
city: Kerrville
country: United States
facility: Sante Clinical Research /ID# 212970
state: Texas
city: San Antonio
country: United States
facility: Stephen Miller, MD PA /ID# 210071
state: Texas
city: Sugar Land
country: United States
facility: Sugar Land Allergy, Asthma, and Immunology Center /ID# 211153
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah /ID# 209001
state: Utah
city: Richmond
country: United States
facility: Clinical Research Partners, LLC /ID# 212262
state: Virginia
city: Spokane
country: United States
facility: Premier Clinical Research /ID# 212142
state: Washington
city: South Charleston
country: United States
facility: West Virginia Research Inst /ID# 212730
state: West Virginia
city: Darlinghurst
country: Australia
facility: Holdsworth House Medical Practice /ID# 214565
state: New South Wales
city: Darlinghurst
country: Australia
facility: The Skin Hospital /ID# 214401
state: New South Wales
city: Woolloongabba
country: Australia
facility: Veracity Clinical Research /ID# 211134
state: Queensland
city: East Melbourne
country: Australia
facility: Sinclair Dermatology /ID# 209395
state: Victoria
city: Victoria Park
country: Australia
facility: Burswood Dermatology /ID# 214875
state: Western Australia
city: Calgary
country: Canada
facility: Kirk Barber Research, CA /ID# 209504
state: Alberta
city: Calgary
country: Canada
facility: Dermatology Research Institute Inc. /ID# 210942
state: Alberta
city: Surrey
country: Canada
facility: Dr. Chih-ho Hong Medical Inc. /ID# 211032
state: British Columbia
city: Surrey
country: Canada
facility: Enverus Medical Research /ID# 209503
state: British Columbia
city: London
country: Canada
facility: Dr. Wei Jing Loo Medicine Prof /ID# 211400
state: Ontario
city: Markham
country: Canada
facility: Lynderm Research Inc. /ID# 209505
state: Ontario
city: Mississauga
country: Canada
facility: DermEdge Research Inc. /ID# 211122
state: Ontario
city: Toronto
country: Canada
facility: Niakosari Medicine Professional Corporation /ID# 211401
state: Ontario
city: Waterloo
country: Canada
facility: K. Papp Clinical Research /ID# 209509
state: Ontario
city: Saint-Jerome
country: Canada
facility: Dre Angelique Gagne-Henley M.D. inc. /ID# 209498
state: Quebec
city: Zagreb
country: Croatia
facility: DermaPlus - Poliklinika za dermatologiju i venerologiju /ID# 209935
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Djecja bolnica Srebrnjak /ID# 209939
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Klinicki bolnicki centar Zagreb /ID# 209976
state: Grad Zagreb
city: Ivanic-Grad
country: Croatia
facility: Naftalan - Specijalna bolnica za medicinsku rehabilitaciju /ID# 209937
state: Zagrebacka Zupanija
city: Brno
country: Czechia
facility: Fakultni Nemocnice Brno /ID# 212968
city: Hradec Kralove
country: Czechia
facility: FN Hradec Kralove /ID# 209116
city: Jihlava
country: Czechia
facility: Nemocnice Jihlava, prispevkova organizace /ID# 209131
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava /ID# 209117
city: Praha
country: Czechia
facility: Fakultni Nemocnice v Motole /ID# 209209
city: Kokkola
country: Finland
facility: Keski-pohjanmaa Central Hospital /ID# 209534
state: Keski-Pohjanmaa
city: Oulu
country: Finland
facility: Oulu University Hospital /ID# 208961
state: Pohjois-Pohjanmaa
city: Mikkeli
country: Finland
facility: Mikkeli Central Hospital /ID# 210125
city: Turku
country: Finland
facility: Pihlajalinna Turku /ID# 209599
city: Lille CEDEX
country: France
facility: CHRU Lille - Hopital Claude Huriez /ID# 209317
state: Hauts-de-France
city: Nantes CEDEX 1
country: France
facility: CHU de Nantes - Hotel Dieu /ID# 208974
state: Pays-de-la-Loire
city: Rouen CEDEX
country: France
facility: Charles Nicolle CHU Rouen /ID# 208973
state: Seine-Maritime
city: Marseille
country: France
facility: Hopital de la Timone /ID# 211245
city: Nice
country: France
facility: Centre Hospitalier Universitaire de Nice - Hopital l'Archet 2 /ID# 213374
city: Reims
country: France
facility: Polyclinique Courlancy /ID# 208975
city: Toulouse
country: France
facility: Hopital Larrey - CHU de Toulouse /ID# 208976
city: Munster
country: Germany
facility: Universitatsklinikum Munster /ID# 210935
state: Niedersachsen
city: Blankenfeld-mahlow
country: Germany
facility: Gemeinschaftspraxis /ID# 211174
city: Darmstadt
country: Germany
facility: Hautklinik Klinikum Darmstadt /ID# 210938
city: Frankfurt
country: Germany
facility: Universitaetsklinikum Frankfurt /ID# 210934
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover /ID# 210939
city: Munich
country: Germany
facility: TU Uniklinik Munchen /ID# 210937
city: Oroshaza
country: Hungary
facility: Oroshazi Korhaz /ID# 210150
state: Bekes
city: Budapest XIII
country: Hungary
facility: Uno Medical Trials Kft /ID# 211177
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont /ID# 210893
city: Kaposvar
country: Hungary
facility: Somogy Megyei Kaposi Mor Oktat /ID# 210149
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai l.sz. Belgyogyaszati Klinika /ID# 210892
city: Dublin
country: Ireland
facility: St Vincent's University Hosp /ID# 208441
city: Waterford
country: Ireland
facility: University Hospital Waterford /ID# 208442
city: Afula
country: Israel
facility: HaEmek Medical Center /ID# 210153
city: Petakh Tikva
country: Israel
facility: Rabin Medical Center /ID# 210012
city: Ramat Gan
country: Israel
facility: Sheba Medical Center /ID# 210013
city: Tel Aviv
country: Israel
facility: Ichilov Medical Center /ID# 210014
city: Milan
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 210632
state: Lombardia
city: Rozzano
country: Italy
facility: IBD Center - IRCCS Istituto Clinico Humanitas /ID# 215726
state: Milano
city: Bologna
country: Italy
facility: A.O. Policlinico Sant'Orsola Malpighi /ID# 209111
city: Brescia
country: Italy
facility: A.O.U. di Brescia /ID# 209115
city: Cagliari
country: Italy
facility: Ospedale San Giovanni di Dio /ID# 209109
city: Modena
country: Italy
facility: AO Univ di Modena /ID# 209110
city: Rome
country: Italy
facility: Policlinico Univ Tor Vergata /ID# 209112
city: Johor Bahru
country: Malaysia
facility: Hospital Sultan Ismail /ID# 211037
state: Johor
city: Muar
country: Malaysia
facility: Hospital Pakar Sultanah Fatimah /ID# 210185
state: Johor
city: Kuala Lumpur
country: Malaysia
facility: UKM Medical Centre /ID# 209178
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Med Ctr /ID# 208861
city: Penang
country: Malaysia
facility: Hospital Pulau Pinang /ID# 210212
city: Putrajaya
country: Malaysia
facility: Hospital Putrajaya /ID# 209177
city: Bergen op Zoom
country: Netherlands
facility: Bravis Ziekenhuis /ID# 208584
state: Noord-Brabant
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum /ID# 208578
state: Noord-Holland
city: Alkmaar
country: Netherlands
facility: Centrum Oosterwal /ID# 209641
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen /ID# 208583
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum /ID# 208582
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht /ID# 208579
city: Auckland
country: New Zealand
facility: Optimal Clinical Trials Ltd /ID# 209475
city: Hamilton
country: New Zealand
facility: Clinical Trials NZ /ID# 215590
city: Wellington
country: New Zealand
facility: Wellington Hospital (Capital and Coast District Health Board) /ID# 215001
city: Trondheim
country: Norway
facility: St. Olavs Hospital HF /ID# 209137
state: Sor-Trondelag
city: Harstad
country: Norway
facility: Universitetssykehuset N-Norge, Harstad /ID# 209105
state: Troms
city: Tromso
country: Norway
facility: Universitetssykehuset N-Norge, Tromso /ID# 209103
state: Troms
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 1 im. dr. A. Jurasza w Bydgoszczy /ID# 211103
state: Kujawsko-pomorskie
city: Lodz
country: Poland
facility: Dermoklinika Medical Center /ID# 211026
state: Lodzkie
city: Krakow
country: Poland
facility: Pratia MCM Krakow /ID# 207444
state: Malopolskie
city: Warsaw
country: Poland
facility: Klinika Ambroziak Sp. z o.o. /ID# 207443
state: Mazowieckie
city: Warszawa
country: Poland
facility: Royalderm Agnieszka Nawrocka /ID# 211015
state: Mazowieckie
city: Bialystok
country: Poland
facility: ClinicMed Daniluk, Nowak Sp.j. /ID# 211112
state: Podlaskie
city: Singapore
country: Singapore
facility: National Skin Centre /ID# 208775
state: Central Singapore
city: Singapore
country: Singapore
facility: National University Hospital /ID# 208774
city: Singapore
country: Singapore
facility: Singapore General Hospital /ID# 208776
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge /ID# 207063
state: Barcelona
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario Dr. Negrin /ID# 208969
state: Las Palmas
city: Manises
country: Spain
facility: Hospital de Manises /ID# 207062
state: Valencia
city: Pontevedra
country: Spain
facility: Complejo Hospitalario Universitario de Pontevedra /ID# 207139
city: Valencia
country: Spain
facility: Hospital Universitario Arnau Vilanova /ID# 207065
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe /ID# 207064
city: Malmö
country: Sweden
facility: Skanes Universitetssjukhus /ID# 206783
state: Skane Lan
city: Stockholm
country: Sweden
facility: Karolinska University Hospital /ID# 207909
city: Taichung City
country: Taiwan
facility: China Medical University Hosp /ID# 209770
state: Taichung
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 208309
state: Taipei
city: Taichung City
country: Taiwan
facility: Chung Shan Medical University /ID# 208311
city: Taipei
country: Taiwan
facility: Taipei Municipal Wan Fang Hospital /ID# 209987
city: Zaporizhzhya
country: Ukraine
facility: Military Hospital of Military-Medical Clinical Center of Southern Region /ID# 210435
state: Zaporizka Oblast
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Skin and Venereal Hospital /ID# 210755
city: Rivne
country: Ukraine
facility: ME "Rivne Regional Dermatology and Venereology Dispensary" of RRC /ID# 210434
city: Brighton
country: United Kingdom
facility: Royal Alex Childrens County Hospital /ID# 209709
state: Brighton And Hove
city: Kirkcaldy
country: United Kingdom
facility: Victoria Hospital /ID# 209853
state: Fife
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Children /ID# 210451
state: Glasgow City
city: London
country: United Kingdom
facility: The Royal Free Hospital /ID# 208659
state: London, City Of
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Found /ID# 208881
state: London, City Of
city: Cardiff
country: United Kingdom
facility: Cardiff & Vale University Health Board /ID# 209745
state: Wales
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References:
citation: Blauvelt A, Teixeira HD, Simpson EL, Costanzo A, De Bruin-Weller M, Barbarot S, Prajapati VH, Lio P, Hu X, Wu T, Liu J, Ladizinski B, Chu AD, Eyerich K. Efficacy and Safety of Upadacitinib vs Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. 2021 Sep 1;157(9):1047-1055. doi: 10.1001/jamadermatol.2021.3023.