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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05507580




Registration number
NCT05507580
Ethics application status
Date submitted
18/08/2022
Date registered
19/08/2022
Date last updated
26/01/2024

Titles & IDs
Public title
A Study to Assess Treat-to-Target and Dosing Flexibility of Oral Upadacitinib Tablets in Adult Participants With Moderate to Severe Atopic Dermatitis
Scientific 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
Secondary ID [1] 0 0
2022-000434-42
Secondary ID [2] 0 0
M22-000
Universal Trial Number (UTN)
Trial acronym
Flex-Up
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atopic Dermatitis 0 0
Condition category
Condition code
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Upadacitinib

Experimental: Double-Blind Treatment Period Dose A - Participants will be administered updadacitinib Dose A once daily (QD) for 12 weeks.

Experimental: Double-Blind Treatment Period Dose B - Participants will be administered updadacitinib Dose B once daily (QD) for 12 weeks.

Experimental: Single-Blinded Treatment Period Arm A - Participants will be administered updadacitinib once daily (QD) for 12 weeks.

Experimental: Single-Blinded Treatment Period Arm B - Participants will be administered updadacitinib once daily (QD) for 12 weeks.

Experimental: Single-Blinded Treatment Period Arm C - Participants will be administered updadacitinib once daily (QD) for 12 weeks.

Experimental: Single-Blinded Treatment Period Arm D - Participants will be administered updadacitinib once daily (QD) for 12 weeks.


Treatment: Drugs: Upadacitinib
Oral tablet
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Achieving Eczema Area and Severity Index (EASI) 90
Timepoint [1] 0 0
Week 24
Secondary outcome [1] 0 0
Percentage of Participants Achieving EASI 75
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Percentage of Participants Achieving EASI 100
Timepoint [2] 0 0
Up to Week 24
Secondary outcome [3] 0 0
Percentage of Participants Achieving EASI 75
Timepoint [3] 0 0
Week 12
Secondary outcome [4] 0 0
Percentage of Participants Achieving EASI 90
Timepoint [4] 0 0
Week 12
Secondary outcome [5] 0 0
Percentage of Participants Achieving EASI 100
Timepoint [5] 0 0
Week 12
Secondary outcome [6] 0 0
Percentage of Participants Achieving EASI 90 and Worst Pruritus Numerical Rating Scale (NRS) of 0 or 1
Timepoint [6] 0 0
Week 12
Secondary outcome [7] 0 0
Percentage of Participants Achieving EASI 90 and Worst Pruritus NRS of 0 or 1
Timepoint [7] 0 0
Week 24
Secondary outcome [8] 0 0
Percentage of Participants Achieving Validated Investigator Global Assessment for Atopic Dermatitis (vlGA-AD) of 0 or 1
Timepoint [8] 0 0
Up to Week 24
Secondary outcome [9] 0 0
Percentage of Participants Achieving Improvement (reduction) in Worst Pruritus NRS of >= 4
Timepoint [9] 0 0
Up to Week 24
Secondary outcome [10] 0 0
Percentage of Participants Achieving Worst Pruritus NRS of 0 or 1
Timepoint [10] 0 0
Up to Week 24
Secondary outcome [11] 0 0
Percentage of Participants Achieving Improvement (reduction) in Dermatology Life Quality Index (DLQI) of >= 4
Timepoint [11] 0 0
Up to Week 24
Secondary outcome [12] 0 0
Percentage of Participants Achieving DLQI of 0 or 1
Timepoint [12] 0 0
Up to Week 24

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
64 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/05/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
9/08/2024
Actual
Sample size
Target
Accrual to date
Final
461
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Holdsworth House Medical Practice /ID# 254028 - Darlinghurst
Recruitment hospital [2] 0 0
Premier Specialist /ID# 246150 - Kogarah
Recruitment hospital [3] 0 0
Veracity Clinical Research /ID# 246154 - Woolloongabba
Recruitment hospital [4] 0 0
North Eastern Health Specialists /ID# 246153 - Campbelltown
Recruitment hospital [5] 0 0
Skin Health Institute Inc /ID# 246146 - Carlton
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
5074 - Campbelltown
Recruitment postcode(s) [5] 0 0
3053 - Carlton
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Bruxelles-Capitale
Country [2] 0 0
Belgium
State/province [2] 0 0
Hainaut
Country [3] 0 0
Belgium
State/province [3] 0 0
Oost-Vlaanderen
Country [4] 0 0
Belgium
State/province [4] 0 0
Gent
Country [5] 0 0
Belgium
State/province [5] 0 0
Liege
Country [6] 0 0
Bulgaria
State/province [6] 0 0
Sofia
Country [7] 0 0
Bulgaria
State/province [7] 0 0
Pleven
Country [8] 0 0
Bulgaria
State/province [8] 0 0
Sofiya
Country [9] 0 0
Canada
State/province [9] 0 0
Alberta
Country [10] 0 0
Canada
State/province [10] 0 0
British Columbia
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
China
State/province [12] 0 0
Beijing
Country [13] 0 0
China
State/province [13] 0 0
Guangdong
Country [14] 0 0
China
State/province [14] 0 0
Liaoning
Country [15] 0 0
China
State/province [15] 0 0
Shanghai
Country [16] 0 0
Germany
State/province [16] 0 0
Hessen
Country [17] 0 0
Germany
State/province [17] 0 0
Nordrhein-Westfalen
Country [18] 0 0
Germany
State/province [18] 0 0
Bad Bentheim
Country [19] 0 0
Germany
State/province [19] 0 0
Bramsche
Country [20] 0 0
Germany
State/province [20] 0 0
Buxtehude
Country [21] 0 0
Germany
State/province [21] 0 0
Darmstadt
Country [22] 0 0
Germany
State/province [22] 0 0
Dresden
Country [23] 0 0
Germany
State/province [23] 0 0
Friedrichshafen
Country [24] 0 0
Germany
State/province [24] 0 0
Halle (Saale)
Country [25] 0 0
Germany
State/province [25] 0 0
Hamburg
Country [26] 0 0
Germany
State/province [26] 0 0
Mahlow
Country [27] 0 0
Germany
State/province [27] 0 0
Mainz
Country [28] 0 0
Hungary
State/province [28] 0 0
Heves
Country [29] 0 0
Hungary
State/province [29] 0 0
Somogy
Country [30] 0 0
Hungary
State/province [30] 0 0
Budapest
Country [31] 0 0
Hungary
State/province [31] 0 0
Debrecen
Country [32] 0 0
Italy
State/province [32] 0 0
Milano
Country [33] 0 0
Italy
State/province [33] 0 0
Umbria
Country [34] 0 0
Italy
State/province [34] 0 0
Ancona
Country [35] 0 0
Italy
State/province [35] 0 0
Brescia
Country [36] 0 0
Italy
State/province [36] 0 0
Chieti
Country [37] 0 0
Italy
State/province [37] 0 0
Milan
Country [38] 0 0
Japan
State/province [38] 0 0
Chiba
Country [39] 0 0
Japan
State/province [39] 0 0
Fukuoka
Country [40] 0 0
Japan
State/province [40] 0 0
Hokkaido
Country [41] 0 0
Japan
State/province [41] 0 0
Kanagawa
Country [42] 0 0
Japan
State/province [42] 0 0
Miyagi
Country [43] 0 0
Japan
State/province [43] 0 0
Tokyo
Country [44] 0 0
Korea, Republic of
State/province [44] 0 0
Gyeonggido
Country [45] 0 0
Korea, Republic of
State/province [45] 0 0
Seoul Teugbyeolsi
Country [46] 0 0
Korea, Republic of
State/province [46] 0 0
Seoul
Country [47] 0 0
Netherlands
State/province [47] 0 0
Amsterdam
Country [48] 0 0
Netherlands
State/province [48] 0 0
Breda
Country [49] 0 0
New Zealand
State/province [49] 0 0
Auckland
Country [50] 0 0
New Zealand
State/province [50] 0 0
Hamilton
Country [51] 0 0
Poland
State/province [51] 0 0
Kujawsko-pomorskie
Country [52] 0 0
Poland
State/province [52] 0 0
Lodzkie
Country [53] 0 0
Poland
State/province [53] 0 0
Malopolskie
Country [54] 0 0
Poland
State/province [54] 0 0
Mazowieckie
Country [55] 0 0
Poland
State/province [55] 0 0
Pomorskie
Country [56] 0 0
Poland
State/province [56] 0 0
Slaskie
Country [57] 0 0
Poland
State/province [57] 0 0
Wielkopolskie
Country [58] 0 0
Poland
State/province [58] 0 0
Bydgoszcz
Country [59] 0 0
Portugal
State/province [59] 0 0
Lisboa
Country [60] 0 0
Portugal
State/province [60] 0 0
Porto
Country [61] 0 0
Slovakia
State/province [61] 0 0
Bratislava
Country [62] 0 0
Slovakia
State/province [62] 0 0
Martin
Country [63] 0 0
Spain
State/province [63] 0 0
Barcelona
Country [64] 0 0
Spain
State/province [64] 0 0
Madrid
Country [65] 0 0
Spain
State/province [65] 0 0
Alicante
Country [66] 0 0
Spain
State/province [66] 0 0
Pontevedra
Country [67] 0 0
Spain
State/province [67] 0 0
Sevilla
Country [68] 0 0
Taiwan
State/province [68] 0 0
Kaohsiung
Country [69] 0 0
Taiwan
State/province [69] 0 0
Taichung
Country [70] 0 0
Taiwan
State/province [70] 0 0
Taipei City
Country [71] 0 0
Taiwan
State/province [71] 0 0
Taipei
Country [72] 0 0
Taiwan
State/province [72] 0 0
Taoyuan City
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Hampshire
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Scotland
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Edinburgh
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Leeds

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05507580
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries