Clinical trial NCT05507580: A Study to Assess Treat-to-Target and Dosing Flexibility of Oral Upadacitinib Tablets in Adult Participants With Moderate to Severe Atopic Dermatitis
Official title: A Phase 3b/4 Randomized, Blinded, Treat-to-Target and Dose-Flexibility Study of Upadacitinib in Adult Subjects With Moderate to Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atopic Dermatitis
Keywords: Atopic Dermatitis (AD)
Upadacitinib
RINVOQ
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2022-08-19
Enrollment: 461
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Atopic dermatitis (AD) is a skin condition that may cause a rash and itching due to inflammation of the skin. Therapies spread over the skin may not be enough to control the AD in trial participants who require systemic anti-inflammatory treatment. This study evaluates the dosing flexibility of upadacitinib in adult participants with moderate to severe AD. Adverse events and change in the disease activity will be assessed.

Upadacitinib is an approved drug for the treatment of moderate to severe/active immune-mediated inflammatory diseases such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis (UC), Crohn's Disease (CD), and AD. The study is comprised of a 35-day Screening Period, a 12-week double-blind period and a 12-week single-blind period. During the double-blind period, participants are placed in 1 of 2 groups, called treatment arms and will be randomized in a 1:1 ratio to receive upadacitinib. At 12 weeks during the single blind period, participants will be blinded to the upadacitinib dose based on their EASI response and reassigned to in 1 of 4 arms. After the last study visit, there is a 30-day follow-up visit. Approximately 454 adult participants ages 18 to 64 with moderate to severe AD who are candidates for systemic therapy will be enrolled at up to 160 sites worldwide.

The study is comprised of a 12-week double-blind period, followed by a 12-week single-blind period. Participants will receive upadacitinib oral tablets once daily for up to 24 weeks.

There may be higher treatment burden for participants in this trial compared to their standard of care (due to study procedures). Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.


Eligibility criteria: Inclusion Criteria:

* Chronic atopic dermatitis (AD) with onset of symptoms at least 3 years prior to Baseline and participant meets Hanifin and Rajka criteria.
* Eczema Area and Severity Index (EASI) score \>= 16, vIGA-AD score \>= 3 and \>= 10% Body Surface Area (BSA) of AD involvement at the Baseline Visit.
* Baseline weekly average of daily Worst Pruritus NRS \>= 4.
* Candidate for systemic treatment defined as prior use of systemic treatment for AD, OR previous inadequate response to TCS, TCI or PDE-4 inhibitors, OR for whom topical treatments are otherwise medically inadvisable.

Exclusion Criteria:

* Participants with current or past history of infection including:

  * Two or more episodes of herpes zoster, or one or more episodes of disseminated herpes zoster;
  * One or more episodes of disseminated herpes simplex (including eczema herpeticum);
  * Human immunodeficiency virus (HIV) infection defined as confirmed positive anti-HIV antibody (HIV Ab) test;
  * Active tuberculosis (TB) or meet TB exclusionary parameters (protocol specified requirements for TB testing);
  * Japan only: Positive result of beta-D-glucan (screening for Pneumocystis jirovecii infection) or two consecutive indeterminate results of beta-D-glucan during the Screening Period;
  * Active infection(s) requiring treatment with intravenous anti-infectives within 30 days, or oral/intramuscular anti-infectives within 14 days prior to the Baseline Visit;
  * Chronic recurring infection and/or active viral infection that, based on the investigator's clinical assessment, makes the participant an unsuitable candidate for the study;
  * COVID-19 infection: In participants who tested positive for COVID, at least 5 days must have passed since a COVID-19 positive test result for study entry of asymptomatic participants. Participants with mild/moderate COVID-19 infection can be enrolled if fever is resolved without use of antipyretics for 24 hours and other symptoms improved, or if 5 days have passed since the COVID-19 positive test result (whichever comes last). Participants may be rescreened if judged to be in good general health, as determined by the investigator based upon the medical history and physical examination.
* Evidence of Hepatitis B virus (HBV) or Hepatitis C virus (HCV).
* Any of the following medical diseases or disorders:

  * Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting, and aorto-coronary bypass surgery;
  * History of an organ transplant which requires continued immunosuppression;
  * History of an allergic reaction or significant sensitivity to constituents of the study drug (and its excipients) and/or other products in the same class;
  * History of gastrointestinal perforation (other than due to appendicitis or mechanical injury), diverticulitis, or significantly increased risk for gastrointestinal perforation per investigator judgment;
  * Conditions that could interfere with drug absorption including but not limited to short bowel syndrome or gastric bypass surgery; participants with a history of gastric banding/segmentation are not excluded;
  * History of malignancy except for successfully treated non-melanoma skin cancer (NMSC) or localized carcinoma in situ of the cervix.

Primary outcomes:
measure: Percentage of Participants Achieving Eczema Area and Severity Index (EASI) 90
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants Achieving EASI 75
timeFrame: Week 24
measure: Percentage of Participants Achieving EASI 100
timeFrame: Up to Week 24
measure: Percentage of Participants Achieving EASI 75
timeFrame: Week 12
measure: Percentage of Participants Achieving EASI 90
timeFrame: Week 12
measure: Percentage of Participants Achieving EASI 100
timeFrame: Week 12
measure: Percentage of Participants Achieving EASI 90 and Worst Pruritus Numerical Rating Scale (NRS) of 0 or 1
timeFrame: Week 12
measure: Percentage of Participants Achieving EASI 90 and Worst Pruritus NRS of 0 or 1
timeFrame: Week 24
measure: Percentage of Participants Achieving Validated Investigator Global Assessment for Atopic Dermatitis (vlGA-AD) of 0 or 1
timeFrame: Up to Week 24
measure: Percentage of Participants Achieving Improvement (reduction) in Worst Pruritus NRS of >= 4
timeFrame: Up to Week 24
measure: Percentage of Participants Achieving Worst Pruritus NRS of 0 or 1
timeFrame: Up to Week 24
measure: Percentage of Participants Achieving Improvement (reduction) in Dermatology Life Quality Index (DLQI) of >= 4
timeFrame: Up to Week 24
measure: Percentage of Participants Achieving DLQI of 0 or 1
timeFrame: Up to Week 24
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: Holdsworth House Medical Practice /ID# 254028
state: New South Wales
city: Kogarah
country: Australia
facility: Premier Specialist /ID# 246150
state: New South Wales
city: Woolloongabba
country: Australia
facility: Veracity Clinical Research /ID# 246154
state: Queensland
city: Campbelltown
country: Australia
facility: North Eastern Health Specialists /ID# 246153
state: South Australia
city: Carlton
country: Australia
facility: Skin Health Institute Inc /ID# 246146
state: Victoria
city: Woluwe-Saint-Lambert
country: Belgium
facility: Cliniques Universitaires UCL Saint-Luc /ID# 245842
state: Bruxelles-Capitale
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi /ID# 245837
state: Hainaut
city: Gent
country: Belgium
facility: AZ Sint-Lucas /ID# 253708
state: Oost-Vlaanderen
city: Maldegem
country: Belgium
facility: Dermatologie Maldegem /ID# 245840
state: Oost-Vlaanderen
city: Liege
country: Belgium
facility: CHU de Liege /ID# 245839
city: Sofiya
country: Bulgaria
facility: UMHAT Alexandrovska EAD /ID# 246594
state: Sofia
city: Pleven
country: Bulgaria
facility: Medical center Cordis /ID# 253310
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Tokuda University Hospital EAD /ID# 246395
city: Sofia
country: Bulgaria
facility: Ambulatory for Specialized Medical Care for skin and venereal diseases /ID# 247027
city: Sofia
country: Bulgaria
facility: Medical center EuroHealth /ID# 246305
city: Sofiya
country: Bulgaria
facility: Medical Center Euroderma /ID# 246736
city: Calgary
country: Canada
facility: Dermatology Research Institute - Blackfoot Trail /ID# 246703
state: Alberta
city: Calgary
country: Canada
facility: Beacon Dermatology Inc /ID# 246705
state: Alberta
city: Edmonton
country: Canada
facility: Rejuvenation Dermatology - Edmonton Downtown /ID# 256790
state: Alberta
city: Edmonton
country: Canada
facility: Alberta DermaSurgery Centre /ID# 247286
state: Alberta
city: Surrey
country: Canada
facility: Dr. Chih-ho Hong Medical Inc. /ID# 246700
state: British Columbia
city: Markham
country: Canada
facility: Lynde Institute for Dermatology /ID# 246699
state: Ontario
city: Peterborough
country: Canada
facility: SKiN Centre for Dermatology /ID# 246702
state: Ontario
city: Waterloo
country: Canada
facility: Private Practice - Dr. Kim Papp Clinical Research /ID# 246698
state: Ontario
city: Beijing
country: China
facility: Beijing Friendship Hospital /ID# 247719
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital /ID# 247842
state: Beijing
city: Guangzhou
country: China
facility: Dermatology Hospital of Southern Medical University /ID# 247951
state: Guangdong
city: Shenyang
country: China
facility: The First Hospital of China Medical University /ID# 247686
state: Liaoning
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University /ID# 247680
state: Shanghai
city: Blankenfelde-Mahlow
country: Germany
facility: Dermatologische Gemeinschaftspraxis Mahlow /ID# 245629
state: Brandenburg
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt /ID# 247028
state: Hessen
city: Frankfurt am Main
country: Germany
facility: Universitaetsklinikum Frankfurt /ID# 245627
state: Hessen
city: Bramsche
country: Germany
facility: Studienzentrum an der Hase GbR Dr. Weyergraf/Dr. Frick/Thomas Heiber /ID# 245636
state: Niedersachsen
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster /ID# 245623
state: Nordrhein-Westfalen
city: Bad Bentheim
country: Germany
facility: Fachklinik Bad Bentheim /ID# 245634
state: Saarland
city: Buxtehude
country: Germany
facility: Elbe Klinikum Buxtehude /ID# 245626
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 248413
city: Friedrichshafen
country: Germany
facility: Derma Study Center Friedrichshafen GmbH /ID# 245640
city: Halle (Saale)
country: Germany
facility: Universitaetsklinikum Halle (Saale) /ID# 245637
city: Hamburg
country: Germany
facility: Dermatologikum Hamburg /ID# 245635
city: Mainz
country: Germany
facility: Dermatologie Quist-BAG Dres. med. Quist PartG /ID# 245628
city: Gyongyos
country: Hungary
facility: Gyongyosi Bugat Pal Korhaz /ID# 246422
state: Heves
city: Kaposvár
country: Hungary
facility: Somogy Varmegyei Kaposi Mor Oktato Korhaz /ID# 246428
state: Somogy
city: Budapest
country: Hungary
facility: Clinexpert Kft /ID# 246427
city: Debrecen
country: Hungary
facility: DERMA-B Egeszsegugyi es Szolgaltato - Debrecen - Gyepusor Utca /ID# 246426
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas /ID# 246630
state: Milano
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia /ID# 246632
state: Umbria
city: Ancona
country: Italy
facility: Duplicate_Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona /ID# 254355
city: Brescia
country: Italy
facility: ASST Spedali civili di Brescia /ID# 246631
city: Chieti
country: Italy
facility: Universita degli Studi Gabriele dAnnunzio /ID# 246629
city: Milan
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 246634
city: Matsudo-Shi
country: Japan
facility: Miyata Dermatology Clinic /ID# 255491
state: Chiba
city: Fukuoka-shi
country: Japan
facility: Fukuoka University Hospital /ID# 255182
state: Fukuoka
city: Obihiro-shi
country: Japan
facility: Takagi Dermatological Clinic Branch /ID# 255181
state: Hokkaido
city: Yokohama-shi
country: Japan
facility: Nomura Dermatology Clinic /ID# 255534
state: Kanagawa
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital /ID# 255183
state: Miyagi
city: Koto-ku
country: Japan
facility: Maruyama Dermatology Clinic /ID# 255441
state: Tokyo
city: Ansan-si
country: Korea, Republic of
facility: Korea University Ansan Hospital /ID# 245653
state: Gyeonggido
city: Bucheon-si
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Bucheon /ID# 245654
state: Gyeonggido
city: Dongjak-gu
country: Korea, Republic of
facility: Chungang University Hospital /ID# 245655
state: Gyeonggido
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital /ID# 245652
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 245651
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center /ID# 245657
state: Seoul Teugbyeolsi
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis /ID# 246397
state: Noord-Brabant
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, locatie AMC /ID# 245673
state: Noord-Holland
city: Epsom
country: New Zealand
facility: Greenlane Clinical Centre /ID# 246556
state: Auckland
city: Hamilton
country: New Zealand
facility: Clinical Trials New Zealand /ID# 246557
state: Manawatu-Wanganui
city: Auckland
country: New Zealand
facility: Aotearoa Clinical Trials /ID# 246559
city: Bydgoszcz
country: Poland
facility: Oftalmika sp. z o.o. /ID# 253429
state: Kujawsko-pomorskie
city: Torun
country: Poland
facility: MICS Centrum Medyczne Torun /ID# 245749
state: Kujawsko-pomorskie
city: Lodz
country: Poland
facility: Dermed Centrum Medyczne Sp. z o.o /ID# 246329
state: Lodzkie
city: Lodz
country: Poland
facility: Santa Sp. z o.o. Santa Familia Centrum Badan, Profilaktyki i Leczenia /ID# 253872
state: Lodzkie
city: Krakow
country: Poland
facility: Centrum Nowoczesnych Terapii Dobry Lekarz Sp. z o.o. /ID# 245836
state: Malopolskie
city: Krakow
country: Poland
facility: CenterMed Krakow Sp. z o.o. /ID# 253940
state: Malopolskie
city: Warsaw
country: Poland
facility: Royalderm Agnieszka Nawrocka /ID# 245746
state: Mazowieckie
city: Warszawa
country: Poland
facility: Klinika Ambroziak Sp. z o.o. /ID# 245748
state: Mazowieckie
city: Gdansk
country: Poland
facility: Centrum Badan Klinicznych PI-House sp. z o.o. /ID# 245741
state: Pomorskie
city: Gdynia
country: Poland
facility: Centrum Medyczne Pratia Gdynia /ID# 245835
state: Pomorskie
city: Katowice
country: Poland
facility: Silmedic Sp. z o.o. /ID# 253863
state: Slaskie
city: Poznan
country: Poland
facility: Specjalistyczna Przychodnia Lekarska Alergo-Med sp. z o.o. /ID# 253846
state: Wielkopolskie
city: Poznań
country: Poland
facility: Specjalistyczny Niepubliczny Zaklad Opieki Zdrowotnej Alergologia Plus /ID# 253508
state: Wielkopolskie
city: Lisboa
country: Portugal
facility: Hospital CUF Descobertas /ID# 245702
state: Regiao Autonoma Da Madeira
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario do Porto, EPE - Hospital Santo Antonio /ID# 245701
state: Regiao Autonoma Da Madeira
city: Lisbon
country: Portugal
facility: Centro Hospitalar de Lisboa Central /ID# 246247
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario de Sao Joao, EPE /ID# 245704
city: Martin
country: Slovakia
facility: Univerzitna nemocnica Martin /ID# 246948
state: Zilinsky Kraj
city: Bratislava
country: Slovakia
facility: Poliklinika Bezrucova (Cliniq s.r.o.) /ID# 247515
city: Bratislava
country: Slovakia
facility: BeneDerma s.r.o. /ID# 247513
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol /ID# 246320
state: Barcelona
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge /ID# 246326
state: Barcelona
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda /ID# 253820
state: Madrid
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante Doctor Balmis /ID# 246270
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor /ID# 246272
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal /ID# 246273
city: Pontevedra
country: Spain
facility: Complejo Hospitalario Universitario de Pontevedra /ID# 246323
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio /ID# 253822
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital /ID# 245710
state: Kaohsiung
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital /ID# 245707
state: Keelung
city: Taipei
country: Taiwan
facility: Taipei Municipal Wan Fang Hospital /ID# 245712
state: Keelung
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 245711
state: Taipei
city: Taipei City
country: Taiwan
facility: Mackay Memorial Hospital /ID# 245713
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital /ID# 245709
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust /ID# 246393
state: Hampshire
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde /ID# 246253
state: Scotland
city: Edinburgh
country: United Kingdom
facility: NHS Lothian /ID# 246245
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust /ID# 246241
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: