A Phase 3 Randomized, Placebo-Controlled, Double-Blind Study to Evaluate Upadacitinib in Adolescent and Adult Subjects With Moderate to Severe Atopic Dermatitis
A Phase 3 Randomized, Placebo-Controlled, Double-Blind Study to Evaluate Upadacitinib in Adolescent and Adult Subjects With Moderate to Severe Atopic Dermatitis
The objective of this study is to assess the efficacy and safety of upadacitinib for the treatment of adolescent and adult participants with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.
This study includes a 35-day screening period, a 16-week double-blind period, a blinded extension period up to Week 260, and a 30-day follow-up visit.
Participants who meet eligibility criteria in the main study will be randomized in a 1:1:1 ratio to receive a daily oral dose of upadacitinib 30 mg or upadacitinib 15 mg or matching placebo. Upon completion of enrollment of 810 participants in the main study, a supplemental study will continue to enroll adolescents (adolescent sub-study) until a total of 180 adolescent participants are enrolled in the overall study (main study + adolescent sub-study).
Randomization for the main study will be stratified by baseline disease severity (validated Investigator Global Assessment scale for Atopic Dermatitis [vIGA-AD] score of moderate [3] versus severe [4]), by geographic region (United States [US]/Puerto Rico/Canada, Japan, China, and Other), and by age (adolescent [ages 12 to 17] versus adult [ages 18 to 75]). The separate randomization for the adolescent sub-study will be stratified by baseline disease severity (moderate [vIGA-AD 3] vs. severe [vIGA-AD 4]) and by geographic region (US/Puerto Rico/Canada and Other).
At Week 16 of the main study and the adolescent sub-study, participants in the placebo group will be re-randomized in a 1:1 ratio to receive daily oral doses of upadacitinib 30 mg or upadacitinib 15 mg in the blinded extension period. In the main study the re-randomization at Week 16 will be stratified by Week 16 50% improvement in Eczema Area and Severity Index [EASI 50] responder [yes/no], geographic region [US/Puerto Rico/Canada, China [Mainland], Japan, and other], and age group [adolescent/adult]. For the adolescent sub-study, the re-randomization will be stratified by EASI 50 responder (Yes/No) and by geographic region (US/Puerto Rico/Canada and Other).
Participants originally randomized to upadacitinib will continue upadacitinib in the extension period at the same dose.
Starting at the Week 4 visit, rescue treatment for AD may be provided at the discretion of the investigator if medically necessary.
The Primary Analysis for the main study will be conducted after all ongoing participants have completed Week 16. In addition, a Primary Analysis for the adolescent population (including the adolescent participants from the main study and the adolescent sub-study) will be conducted after all ongoing adolescent participants have completed Week 16.
Following the interim analysis, significant noncompliance was identified at a clinical site. As a result, all data from the site, including data from 10 adolescent participants, has been excluded from the final analysis of the outcome measures as appropriate.
Inclusion Criteria:
Body weight of ≥ 40 kg at Baseline Visit for participants between ≥ 12 and < 18 years of age
Chronic atopic dermatitis (AD) with onset of symptoms at least 3 years before Baseline Visit and subject meets Hanifin and Rajka criteria.
Active moderate to severe AD defined by:
Candidate for systemic therapy or have recently required systemic therapy for AD
Subject has applied a topical emollient (moisturizer) twice daily for at least 7 days before the Baseline Visit.
Documented history of inadequate response to topical corticosteroids (TCS) or topical calcineurin inhibitor (TCI) or documented systemic treatment for AD within 6 months before Baseline Visit
Exclusion Criteria:
Los Angeles, California 90025-7014, United States
Mission Viejo, California 92691-6410, United States
Washington D.C., District of Columbia 20037, United States
Chicago, Illinois 60611-2927, United States
Charleston, South Carolina 29414, United States
Ciudad Autonoma de Buenos Aire, Ciuadad Autonoma de Buenos Aires 1425, Argentina
Ciudad Autonoma de Buenos Aire, Ciuadad Autonoma de Buenos Aires 1425, Argentina
Banja Luka, Republika Srpska 78000, Bosnia and Herzegovina
Banja Luka, Republika Srpska 78000, Bosnia and Herzegovina
Hamilton, Ontario L8S 4K1, Canada
Guangzhou, Guangdong 510120, China
Guangzhou, Guangdong 510630, China
Shanghai, Shanghai Municipality 200065, China
Hangzhou, Zhejiang 310009, China
Wuhan, 420022, China
Montería, Departamento de Córdoba 230002, Colombia
Osijek, County of Osijek-Baranja 31000, Croatia
Copenhagen NV, Capital Region 2400, Denmark
Munich, Bavaria 80802, Germany
Kiel, Schleswig-Holstein 24105, Germany
Nagakute-shi, Aichi-ken 480-1195, Japan
Fukuoka, Fukuoka 815-8588, Japan
Ogaki-shi, Gifu 503-8502, Japan
Obihiro-shi, Hokkaido 080-0013, Japan
Kyoto, Kyoto 602-8566, Japan
Sakai-shi, Osaka 5938324, Japan
Shinagawa-ku, Tokyo 141-8625, Japan
Chuo-shi, Yamanashi 409-3821, Japan
Kota Kinabalu, Division Pantai Barat Utara, Sabah 88200, Malaysia
Chelyabinsk, Chelyabinsk Oblast 454048, Russia
Saratov, Saratov Oblast 410012, Russia
Yekaterinburg, Sverdlovsk Oblast 620076, Russia
Lausanne, Canton of Vaud 1011, Switzerland
Lausanne, Canton of Vaud 1011, Switzerland
Istanbul, 34098, Turkey (Türkiye)
Zaporizhzhya, Zaporizhzhia Oblast 69063, Ukraine
London, London, City of SE1 9RT, United Kingdom