This is a study to evaluate safety and efficacy of Upadacitinib comparing to Dupilumab in children from 2 to less than 12 years of age with Moderate to Severe Atopic Dermatitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AbbVie Deutschland GmbH & Co. KG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

3 Dec 2024 → ongoing

Decision date (initial)

2024-10-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The study objective is to assess the efficacy and safety of upadacitinib, compared with dupilumab at the label-indicated dose and frequency, in pediatric subjects 2 to < 12 years of age with moderate to severe AD who are candidates for systemic therapy.

The primary efficacy objective for other than US is to assess the proportion of subjects achieving EASI 75 response at Week 16 in those treated with upadacitinib 15 mg daily adult equivalent dose compared to subjects treated with dupilumab in the ITT population.

The primary efficacy objective for US and China is to assess the proportion of subjects achieving vIGA-AD 0 or 1 with a reduction from Baseline of ≥ 2 points at Week 16 based on the ITT population for each treatment arm. Dupilumab will be a reference arm for upadacitinib 15 mg daily adult equivalent dose.

Secondary objectives 1

1. The secondary efficacy objective is to assess the proportion of subjects who achieve the dichotomous secondary endpoints and the mean of continuous endpoints as specified in Section 3.3 based on the ITT population for each treatment arm. Dupilumab will be a reference arm for both upadacitinib 15 mg and 7.5 mg daily adult equivalent doses and the higher dose of upadacitinib will be a reference arm for the lower dose.

Conditions and MedDRA coding

Dermatitis atopic

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001741-PIP04-17

Plan to share IPD

Yes

IPD plan description

AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information. To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/ For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Subject must be a pediatric individual 2 to < 12 years old at Screening and Baseline Visit. Note: Only subjects 6 to < 12 years of age will be enrolled in the US. Outside of the US, subjects 2 to < 6 years of age may be enrolled where allowed.
2. Subject must be at 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.
3. Subject must meet the following disease activity criteria at Baseline Visit: • 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]); and • ≥ 10% BSA of AD involvement. • Baseline weekly average of daily WIS (patient-reported) or WSI-NRS (caregiver-reported) ≥ 4. The Baseline weekly average will be calculated from the 7 consecutive days immediately preceding the Baseline Visit. A minimum of 4 daily scores out of the 7 days is needed.
4. Subject must satisfy at least one of the following criteria (Note: More than 1 criterion may apply to an individual subject. All applicable criteria for each individual subject should be reported.): • To be included in the Randomized Cohort (Note: Subjects must have severe AD [vIGA-AD = 4] in countries where dupilumab is approved only for severe AD): a. [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, SCORAD > 50, EASI score > 21, or vIGAAD> 3). Note: Enrolled subjects eligible under Criterion 6a will be capped at 50% of the total enrollment. b. For dupilumab-naïve subjects: 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). c. 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. d. For dupilumab-exposed subjects: 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 subject's 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.
5. Subjects with periocular AD involvement must be willing to undergo preliminary ophthalmology assessment prior to the Baseline Visit.

Exclusion criteria 5

1. Subjects who have used topical treatments for AD (except for topical emollient treatments) including but not limited to TCS, TCI, or topical PDE-4 inhibitors, within 7 days of the Baseline Visit.
2. Subjects who have used 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, IFN-γ, 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
3. Subjects who have used any oral or topical JAK inhibitor (including but not limited to baricitinib, upadacitinib, ruxolitinib, and delgocitinib) anytime before the study
4. Known history of retinal detachment, previous cataract surgery, previous significant ocular trauma, or a known congenital ocular abnormality.
5. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Percentage of Participants Achieving a 75% Reduction in Eczema Area and Severity Index Score (EASI 75) at Week 16 (other than US)
2. Achievement of validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) 0 or 1 with a reduction from Baseline of ≥ 2 points at Week 16 (US and China only, descriptive)

Secondary endpoints 12

1. Percentage of participants achieving validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 (on a 5-point scale) with a reduction from Baseline of ≥ 2 Points at Week 16 (other than US and China)
2. Percentage of participants achieving a 50% reduction from Baseline in EASI score (EASI 50) at Week 16
3. Percentage of participants achieving Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 (on a 5-point scale) with a reduction from Baseline of ≥ 2 Points at Week 52
4. Percentage of participants achieving Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) of 0 or 1 (on a 5-point scale) with a reduction from Baseline of ≥ 2 Points at Week 160
5. Percentage of participants achieving an improved (reduced) Patient Oriented Eczema Measure (POEM) of ≥ 4 points at Week 16 from participants with POEM ≥ 4 at Baseline
6. Percentage of for participants ≥ 4 years of age with a Baseline Children's Dermatology Life Quality Index (CDLQI) score of >1 participants achieving a CDLQI score of 0 or 1 at Week 8
7. Percentage of for participants ≥ 4 years of age with a Baseline Children's Dermatology Life Quality Index (CDLQI) score of >1 participants achieving a CDLQI score of 0 or 1 at Week 16
8. Percent change in Scoring Atopic Dermatitis (SCORAD) from Baseline at Week 16
9. Use of topical or systemic rescue therapy from Baseline to Week 16
10. Number of days on rescue topical corticosteroid or topical calcineurin inhibitor from Baseline to Week 16
11. Percentage of participants achieving a EASI 75 response at Week 16 for low dose Dupilumab daily adult equivalent dose
12. Achievement of EASI 75 response at Week 16 (US)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation

AbbVie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Public contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Third parties 8

Locations

12 EU/EEA countries · 53 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 140 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications