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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06461897




Registration number
NCT06461897
Ethics application status
Date submitted
12/06/2024
Date registered
17/06/2024
Date last updated
17/01/2025

Titles & IDs
Public title
A Study to Assess Adverse Events and Change in Disease Activity Comparing Oral Upadacitinib to Subcutaneous Dupilumab in Children From 2 to Less Than 12 Years of Age With Moderate to Severe Atopic Dermatitis
Scientific title
A Phase 3, Open-label, Efficacy-Assessor-Blinded Study, Comparing the Safety and Efficacy of Upadacitinib to Dupilumab in Children From 2 to Less Than 12 Years of Age With Moderate to Severe Atopic Dermatitis
Secondary ID [1] 0 0
2023-504713-76-00
Secondary ID [2] 0 0
M17-380
Universal Trial Number (UTN)
Trial acronym
Start 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
Treatment: Drugs - Dupilumab

Experimental: Dupi-IR Cohort - Participants in this cohort will receive upadacitinib medium dose.

Experimental: Randomized Cohort - Participants in the Randomized Cohort will be randomized to receive either medium dose upadacitinib daily adult equivalent dose, low dose upadacitinib daily adult equivalent dose or dupilumab every 2 weeks or 4 weeks (at the label-indicated dose and frequency).


Treatment: Drugs: Upadacitinib
Oral Tablet or Oral Solution

Treatment: Drugs: Dupilumab
Subcutaneous Injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Achieving a 75% Reduction from Baseline in Eczema Area and Severity Index 75 (EASI 75) Score (other than US)
Timepoint [1] 0 0
At Week 16
Primary outcome [2] 0 0
Percentage of participants achieving validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) 0 or 1 with a reduction from Baseline of = 2 points (US and China only, descriptive)
Timepoint [2] 0 0
Week 16
Primary outcome [3] 0 0
Number of Participants with Adverse Events (AEs)
Timepoint [3] 0 0
Up to Approximately Week 172
Secondary outcome [1] 0 0
Percentage of Participants Achieving a 75% Reduction from Baseline in EASI 75 Score (US)
Timepoint [1] 0 0
At Week 16
Secondary outcome [2] 0 0
Percentage of participants achieving vIGA-AD of 0 or 1 (on a 5-point scale) with a reduction from Baseline of = 2 Points
Timepoint [2] 0 0
At Week 16
Secondary outcome [3] 0 0
Percentage of participants achieving a 50% reduction from Baseline in EASI 50 score
Timepoint [3] 0 0
At Week 16
Secondary outcome [4] 0 0
Percentage of participants achieving vIGA-AD of 0 or 1 (on a 5-point scale) with a reduction from Baseline of = 2 Points
Timepoint [4] 0 0
At Week 52
Secondary outcome [5] 0 0
Percentage of participants achieving vIGA-AD of 0 or 1 (on a 5-point scale) with a reduction from Baseline of = 2 Points
Timepoint [5] 0 0
At Week 160
Secondary outcome [6] 0 0
Percentage of participants achieving an improved (reduced) Patient Oriented Eczema Measure (POEM) of = 4 points from from participants with POEM = 4 at Baseline
Timepoint [6] 0 0
At Week 16
Secondary outcome [7] 0 0
Percentage of participants = 4 years of age with a Baseline Children's Dermatology Life Quality Index (CDLQI) score of >1 achieving a CDLQI score of 0 or 1
Timepoint [7] 0 0
At Week 8
Secondary outcome [8] 0 0
Percentage of participants = 4 years of age with a Baseline CDLQI score of >1 achieving a CDLQI score of 0 or 1
Timepoint [8] 0 0
At Week 16
Secondary outcome [9] 0 0
Percent change in Scoring Atopic Dermatitis (SCORAD) from Baseline
Timepoint [9] 0 0
At Week 16
Secondary outcome [10] 0 0
Use of topical or systemic rescue therapy from Baseline to Week 16
Timepoint [10] 0 0
Baseline to Week 16
Secondary outcome [11] 0 0
Number of days on rescue topical corticosteroid or topical calcineurin inhibitor from Baseline to Week 16
Timepoint [11] 0 0
Baseline to Week 16
Secondary outcome [12] 0 0
Percentage of participants achieving a EASI 75 response for low dose upadacitinib daily adult equivalent dose
Timepoint [12] 0 0
At Week 16

Eligibility
Key inclusion criteria
* A minimum weight of 10 kg and weight and height > 5th percentile for their age according to local standard growth charts at the Baseline Visit.
* Atopic Dermatitis (AD), according to Hanifin and Rajka criteria, with onset of symptoms at least 6 months prior to Baseline.
* Eczema Area and Severity Index (EASI) score >= 16; vIGA-AD score >= 3 (Note: In countries where dupilumab is only approved for severe AD, subjects to be included in the Randomized Cohort should have severe AD [vIGA-AD = 4]); >= 10% Body Surface Area of AD involvement at the Baseline Visit; and Baseline weekly average of daily Worst Itch Scale (WIS) or Worst Scratch/Itch numerical rating scale (WSI-NRS) >= 4.
* Participant must satisfy at least one of the following criteria (Note: More than 1 criterion may apply to an individual participant. All applicable criteria for each individual participant should be reported):
* To be included in the Randomized Cohort (Note: Participants must have severe AD [vIGA-AD = 4] in countries where dupilumab is approved only for severe AD.):

1. [For all countries except US] Documented history of inadequate response or intolerance to TCS and/or TCI OR for whom use of one or more of these topical treatments is medically inadvisable (e.g., high disease burden, Scoring Atopic Dermatitis (SCORAD) > 50, EASI score > 21, or vIGA-AD > 3).
2. For dupilumab-naïve participants: History of inadequate response to a systemic therapy for AD other than dupilumab or oral corticosteroids or for whom the available systemic treatments are otherwise medically inadvisable (e.g., because of important side effects or safety risks).
3. History of inadequate response to 2 or more courses of oral corticosteroid therapy given for >= 14 days within 6 months prior to Screening or history of oral corticosteroid rebound, defined as recurrence of AD symptoms within 4 months after its discontinuation.
4. For dupilumab-exposed participants: Prior exposure to dupilumab without documented history of inadequate response or intolerance (i.e., discontinuation of dupilumab for a non-medical reason, such as, but not limited to, non-coverage or loss of coverage for the drug by health insurance, or other logistic challenges [not safety- or efficacy-related] precluding the participants continued access to dupilumab).
* To be included in the Dupi-IR/Dupi-Medically Inadvisable Cohort:

* Previous inadequate response or intolerance to dupilumab OR
* Dupilumab is medically inadvisable (e.g., allergy to a component of dupilumab, etc.) AND a documented history of inadequate response or intolerance to TCS and/or TCI.
Minimum age
2 Years
Maximum age
11 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Current or past history of other active skin diseases (e.g., psoriasis or Netherton syndrome or lupus erythematosus) or skin infections (bacterial, fungal, or viral) requiring systemic treatment within 4 weeks of the Baseline Visit or which would interfere with the appropriate assessment of AD lesions.
* Have used topical treatments for AD (except for topical emollient treatments) including but not limited to TCS, TCI, or topical phosphodiesterase type 4 (PDE-4) inhibitors, within 7 days of the Baseline Visit or any the following prohibited concomitant AD treatments within the specified timeframes below prior to the Baseline Visit:

* Systemic therapy for AD, including but not limited to corticosteroids, methotrexate, cyclosporine, azathioprine, PDE-4 inhibitors, interferon-?, and mycophenolate mofetil within 4 weeks;
* Dupilumab within 8 weeks;
* Targeted biologic treatments (other than dupilumab) within 5 half-lives (if known) or within 12 weeks, whichever is longer;
* Phototherapy treatment, laser therapy, tanning booth, or extended sun exposure that could affect disease severity or interfere with disease assessments within 4 weeks.
* Known history of retinal detachment, previous cataract surgery, previous significant ocular trauma, or a known congenital ocular abnormality.
* For Randomized Cohort: diagnosed active parasitic infection; suspected or high risk of parasitic infection, unless clinical and (if necessary) laboratory assessment have ruled out active infection before randomization.

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 assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/08/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2030
Actual
Sample size
Target
675
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Monash Health - Monash Medical Centre /ID# 267149 - Clayton
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Idaho
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Nebraska
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
South Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah
Country [14] 0 0
Austria
State/province [14] 0 0
Steiermark
Country [15] 0 0
Austria
State/province [15] 0 0
Salzburg
Country [16] 0 0
Austria
State/province [16] 0 0
Wien
Country [17] 0 0
Bulgaria
State/province [17] 0 0
Pleven
Country [18] 0 0
Bulgaria
State/province [18] 0 0
Sofiya
Country [19] 0 0
Canada
State/province [19] 0 0
Alberta
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
Croatia
State/province [21] 0 0
Grad Zagreb
Country [22] 0 0
Croatia
State/province [22] 0 0
Rijeka
Country [23] 0 0
France
State/province [23] 0 0
Argenteuil
Country [24] 0 0
France
State/province [24] 0 0
Nantes
Country [25] 0 0
Germany
State/province [25] 0 0
Bayern
Country [26] 0 0
Hungary
State/province [26] 0 0
Bekes
Country [27] 0 0
Hungary
State/province [27] 0 0
Csongrad
Country [28] 0 0
Hungary
State/province [28] 0 0
Hajdu-Bihar
Country [29] 0 0
Israel
State/province [29] 0 0
H_efa
Country [30] 0 0
Israel
State/province [30] 0 0
HaDarom
Country [31] 0 0
Israel
State/province [31] 0 0
HaMerkaz
Country [32] 0 0
Israel
State/province [32] 0 0
Tel-Aviv
Country [33] 0 0
Israel
State/province [33] 0 0
Yerushalayim
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Gyeonggido
Country [35] 0 0
Netherlands
State/province [35] 0 0
Noord-Holland
Country [36] 0 0
Poland
State/province [36] 0 0
Kujawsko-pomorskie
Country [37] 0 0
Poland
State/province [37] 0 0
Malopolskie
Country [38] 0 0
Poland
State/province [38] 0 0
Mazowieckie
Country [39] 0 0
Poland
State/province [39] 0 0
Podlaskie
Country [40] 0 0
Poland
State/province [40] 0 0
Slaskie
Country [41] 0 0
Poland
State/province [41] 0 0
Wielkopolskie
Country [42] 0 0
Portugal
State/province [42] 0 0
Coimbra
Country [43] 0 0
Portugal
State/province [43] 0 0
Porto
Country [44] 0 0
Puerto Rico
State/province [44] 0 0
Bayamon
Country [45] 0 0
Puerto Rico
State/province [45] 0 0
Carolina
Country [46] 0 0
Slovakia
State/province [46] 0 0
Kosicky Kraj
Country [47] 0 0
Spain
State/province [47] 0 0
Barcelona
Country [48] 0 0
Spain
State/province [48] 0 0
Madrid
Country [49] 0 0
Spain
State/province [49] 0 0
Valencia
Country [50] 0 0
Spain
State/province [50] 0 0
Zaragoza
Country [51] 0 0
Taiwan
State/province [51] 0 0
Kaohsiung
Country [52] 0 0
Taiwan
State/province [52] 0 0
Taipei
Country [53] 0 0
Taiwan
State/province [53] 0 0
New Taipei City
Country [54] 0 0
Taiwan
State/province [54] 0 0
Taipei City
Country [55] 0 0
Taiwan
State/province [55] 0 0
Taoyuan City
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Devon
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Greater London
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Lanarkshire

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. Topical therapies applied over the skin may not be enough to control the AD in trial participants who require systemic anti-inflammatory treatment. This study compares upadacitinib to dupilumab in pediatric participants with moderate to severe AD who are candidates for systemic therapy. Adverse events and change in the disease activity will be assessed.

Upadacitinib is an approved drug for treating AD patients aged 12 or older. Participants will receive upadacitinib (given as daily dose) or dupilumab (given at label indicated dose every 2 or 4 weeks). Participants will be stratified depending on disease severity, age and response to previous treatment. There is 1 in 5 chance for participants to receive dupilumab during the randomized cohort. Approximately 675 participants aged 2 to less than 12 years of age will be enrolled in this study at approximately 150 sites worldwide. The study population (As defined by participants age or prior treatment) to be enrolled in the study is dependent on local regulatory requirement and/or agreement.

Participants will receive upadacitinib oral tablets once daily (or oral solution twice a day) for 160 weeks, or dupilumab as per its label for 52 weeks, and followed for 30 days after the last dose of upadacitinib and at least 12 weeks after the last dose of dupilumab.

There may be higher treatment burden for participants in this trial compared to their standard of care . Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by clinical assessments, blood tests, checking for side effects and completing questionnaires.
Trial website
https://clinicaltrials.gov/study/NCT06461897
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
ABBVIE CALL CENTER
Address 0 0
Country 0 0
Phone 0 0
844-663-3742
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06461897