A Study to Compare Safety and Efficacy of Upadacitinib to Dupilumab in Adult Participants With Moderate to Severe Atopic Dermatitis

Atopic Dermatitis Clinical Trial

— Heads Up  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03738397
• Other study ID #: M16-046
• Secondary ID: 2018-002264-57
• Status: Completed
• Phase: Phase 3
• Start date: February 21, 2019
• Est. completion date: December 9, 2020

Study information

• Verified date: February 2024
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 673
• Est. completion date: December 9, 2020
• Est. primary completion date: August 27, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 76 Years

Eligibility

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.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Biological:
• Upadacitinib
Extended release tablet
• Dupilumab
Dupilumab is administered as a subcutaneous (SC) injection

Drug:
• Placebo to dupilumab
Placebo administered as a subcutaneous injection
• Placebo to upadacitinib
Tablet

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Croatia,  Czechia,  Finland,  France,  Germany,  Hungary,  Ireland,  Israel,  Italy,  Malaysia,  Netherlands,  New Zealand,  Norway,  Poland,  Singapore,  Spain,  Sweden,  Taiwan,  Ukraine,  United Kingdom, 

References & Publications (1)

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: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving a 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75) at Week 16	EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema).; The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.	Baseline and Week 16
Secondary	Percent Change From Baseline in Worst Pruritus Numerical Rating Scale (NRS) Score at Week 16	The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).; The percent change from Baseline was calculated from a rolling weekly average; a negative change from Baseline indicates improvement.	Baseline (Week 0) to Week 16
Secondary	Percentage of Participants Achieving a 100% Reduction From Baseline in EASI Score (EASI 100) at Week 16	EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema).; The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.	Baseline and Week 16
Secondary	Percentage of Participants Achieving a 90% Reduction From Baseline in EASI Score (EASI 90) at Week 16	EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema).; The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.	Baseline and Week 16
Secondary	Percent Change From Baseline in Worst Pruritus Numerical Rating Scale (NRS) Score at Week 4	The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).; The percent change from Baseline was calculated from a rolling weekly average; a negative change from Baseline indicates improvement.	Baseline (Week 0) to Week 4
Secondary	Percentage of Participants Achieving a 75% Reduction From Baseline in EASI Score at Week 2	EASI is a tool used to measure the extent (area) and severity of atopic eczema based on assessments of the head/neck, trunk, upper limbs and lower limbs. For each region the area score is recorded as the percentage of skin affected by eczema. For each region, the severity score is calculated as the sum of the intensity scores (scored as none [0], mild [1], moderate [2], or severe [3]) for redness (erythema, inflammation), thickness (induration, papulation, swelling - acute eczema), scratching (excoriation), and lichenification (lined skin, prurigo nodules - chronic eczema).; The total EASI score for each region is calculated by multiplying the severity score by the area score, with adjustment for the proportion of the body region to the whole body. The final EASI score is the sum of the 4 region scores and ranges from 0 to 72 where higher scores represent worse disease.	Baseline and Week 2
Secondary	Percent Change From Baseline in Worst Pruritus Numerical Rating Scale (NRS) Score at Week 1	The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).; The percent change from Baseline was calculated from a rolling weekly average; a negative change from Baseline indicates improvement.	Baseline (Week 0) to Week 1
Secondary	Percentage of Participants Achieving a Reduction of = 4 Points From Baseline in Worst Pruritus NRS at Week 16	The Worst Pruritus NRS is an assessment tool that participants used to report the intensity of their pruritus during a 24-hour recall period using an electronic hand-held device. Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on an 11-point scale from 0 (no itch) to 10 (worst imaginable itch).	Baseline and Week 16

External Links

•   This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.