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

Official 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

Overview

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.

Interventions

• Drug Upadacitinib
  Oral Tablet or Oral Solution
• Drug Dupilumab
  Subcutaneous Injection

Primary outcome measures

• Percentage of Participants Achieving a 75% Reduction from Baseline in Eczema Area and Severity Index 75 (EASI 75) Score (other than US) [Time frame: At Week 16]
• 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) [Time frame: Week 16]
• Number of Participants with Adverse Events (AEs) [Time frame: Up to Approximately Week 172]

Secondary outcome measures (12)

• Percentage of Participants Achieving a 75% Reduction from Baseline in EASI 75 Score (US) [Time frame: At Week 16]
• Percentage of participants achieving vIGA-AD of 0 or 1 (on a 5-point scale) with a reduction from Baseline of ≥ 2 Points [Time frame: At Week 16]
• Percentage of participants achieving a 50% reduction from Baseline in EASI 50 score [Time frame: At Week 16]
• Percentage of participants achieving vIGA-AD of 0 or 1 (on a 5-point scale) with a reduction from Baseline of ≥ 2 Points [Time frame: At Week 52]
• Percentage of participants achieving vIGA-AD of 0 or 1 (on a 5-point scale) with a reduction from Baseline of ≥ 2 Points [Time frame: At Week 160]
• Percentage of participants achieving an improved (reduced) Patient Oriented Eczema Measure (POEM) of ≥ 4 points from from participants with POEM ≥ 4 at Baseline [Time frame: At Week 16]
• 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 [Time frame: At Week 8]
• Percentage of participants ≥ 4 years of age with a Baseline CDLQI score of >1 achieving a CDLQI score of 0 or 1 [Time frame: At Week 16]
• Percent change in Scoring Atopic Dermatitis (SCORAD) from Baseline [Time frame: At Week 16]
• Use of topical or systemic rescue therapy from Baseline to Week 16 [Time frame: Baseline to Week 16]
• Number of days on rescue topical corticosteroid or topical calcineurin inhibitor from Baseline to Week 16 [Time frame: Baseline to Week 16]
• Percentage of participants achieving a EASI 75 response for low dose upadacitinib daily adult equivalent dose [Time frame: At Week 16]

Eligibility criteria

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.):

• \[For all countries except US\] 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).
• 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).
• 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.
• 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.

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-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.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 31 centers

• Applied Research Center and Wellness Clinic /ID# 268547 — Little Rock
• Stanford University School of Medicine /ID# 269622 — Palo Alto
• Integrative Skin Science and Research /ID# 265108 — Sacramento
• Clearlyderm Dermatology - West Boca /ID# 266323 — Boca Raton
• Pediatric Skin Research - Coral Gables /ID# 266308 — Coral Gables
• Neoclinical Research - Hialeah /ID# 269694 — Hialeah
• Emory University School Of Medicine - Atlanta /ID# 268832 — Atlanta
• Cleaver Medical Group Dermatology /ID# 265099 — Dawsonville
• … and 23 more centers

Canada · 10 centers

• Dermatology Research Institute - Blackfoot Trail /ID# 266744 — Calgary
• Rejuvenation Dermatology - Edmonton Downtown /ID# 267871 — Edmonton
• British Columbia Children and Women's Hospital and Health Centre /ID# 265395 — Vancouver
• Maritime Dermatology /ID# 267359 — Halifax
• Leader Research /ID# 266745 — Hamilton
• Triple A Lab Inc /ID# 266615 — Hamilton
• Lynderm Research Inc /ID# 267006 — Markham
• Allergy Research Canada /ID# 270230 — Niagara Falls
• … and 2 more centers

China · 10 centers

• Beijing Children's Hospital /ID# 266350 — Beijing
• Children's Hospital Affiliated to Chongqing Medical University /ID# 266876 — Yuzhong District
• Xiamen Children's Hospital /ID# 266384 — Xiamen
• Shenzhen Children's Hospital /ID# 266401 — Shenzhen
• Henan Children's Hospital Zhengzhou Children's Hospital /ID# 266832 — Zhengzhou
• Hunan Children's Hospital /ID# 266365 — Changsha
• Dalian Women and Children's Medical Group /ID# 266675 — Dalian
• Chengdu Women and Children Center Hospital /ID# 266402 — Chengdu
• … and 2 more centers

Poland · 10 centers

Center list to be confirmed — check the primary protocol.

France · 8 centers

• CHU Toulouse - Hopital Larrey /ID# 255048 — Toulouse
• Centre Hospitalier Regional Universitaire de Nancy - Hopitaux de Brabois /ID# 265455 — Vandœuvre-lès-Nancy
• Chu Bordeaux - Hopital Pellegrin /ID# 266818 — Bordeaux
• Centre Hospitalier Universitaire de Nantes - L' Hopital l'hotel-Dieu /ID# 265449 — Nantes
• … and 4 more centers

United Kingdom · 8 centers

Center list to be confirmed — check the primary protocol.

South Korea · 6 centers

Center list to be confirmed — check the primary protocol.

Brazil · 5 centers

• Irmandade da Santa Casa de Misericordia de Porto Alegre /ID# 267455 — Porto Alegre
• Hospital e Maternidade Celso Pierro - PUC-Campinas /ID# 266965 — Campinas
• Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto /ID# 266964 — Ribeirão Preto
• Clinica de Alergia Martti Antila /ID# 266197 — Sorocaba
• Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao /ID# 266667 — São Paulo

Croatia · 5 centers

• Klinika za dječje bolesti Zagreb /ID# 264936 — Zagreb
• Poliklinika DermaPlus /ID# 265724 — Zagreb
• Poliklinika Solmed /ID# 265070 — Zagreb
• Specialty Hospital Medico /ID# 266116 — Rijeka
• Klinicki Bolnicki Centar Split /ID# 265359 — Split

Germany · 5 centers

Center list to be confirmed — check the primary protocol.

Israel · 5 centers

Center list to be confirmed — check the primary protocol.

Slovakia · 5 centers

Center list to be confirmed — check the primary protocol.

Spain · 5 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 5 centers

Center list to be confirmed — check the primary protocol.

Argentina · 4 centers

• Sanatorio 9 de Julio /ID# 267678 — San Miguel de Tucumán
• Conexa Investigacion Clinica /ID# 268728 — Buenos Aires
• Instituto de Neumonologia y Dermatologia /ID# 266146 — Buenos Aires
• Psoriahue - Buenos Aires /ID# 267737 — Buenos Aires

Australia · 3 centers

• The Children's Hospital at Westmead /ID# 265430 — Westmead
• Monash Health - Monash Medical Centre - Clayton /ID# 267149 — Clayton
• Institute for Skin, Health and Immunity /ID# 266158 — Mitcham

Austria · 3 centers

• Medizinische Universitaet Graz /ID# 262741 — Graz
• Landeskrankenhaus Salzburg-Universitaetsklinikum der PMU (LKH) /ID# 265427 — Salzburg
• Medizinische Universitaet Wien /ID# 265417 — Vienna

Chile · 3 centers

• Clinica Dermacross /ID# 266309 — Vitacura
• Fundacion Innovacion Cardiovascular /ID# 266742 — Independencia
• Centro De Especialidades Dermatologicas /ID# 267483 — Viña del Mar

Hungary · 3 centers

Center list to be confirmed — check the primary protocol.

Italy · 3 centers

Center list to be confirmed — check the primary protocol.

Portugal · 3 centers

Center list to be confirmed — check the primary protocol.

Bulgaria · 2 centers

• UMHAT Alexandrovska EAD /ID# 265256 — Sofiya
• Medical Center Cordis /ID# 265250 — Pleven

Mexico · 2 centers

Center list to be confirmed — check the primary protocol.

Netherlands · 2 centers

Center list to be confirmed — check the primary protocol.

Puerto Rico · 2 centers

Center list to be confirmed — check the primary protocol.

Singapore · 2 centers

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06461897 · M17-380 · 2023-504713-76-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗