Clinical trial NCT06461897: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Atopic Dermatitis
Keywords: Atopic Dermatitis
Upadacitinib
RINVOQ
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2024-06-17
Enrollment: 675
Sex: ALL
Minimum age (years): 2
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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. 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.


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.):

  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.

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.

Primary outcomes:
measure: Percentage of Participants Achieving a 75% Reduction from Baseline in Eczema Area and Severity Index 75 (EASI 75) Score (other than US)
timeFrame: At Week 16
measure: 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)
timeFrame: Week 16
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to Approximately Week 172
Secondary outcomes:
measure: Percentage of Participants Achieving a 75% Reduction from Baseline in EASI 75 Score (US)
timeFrame: At Week 16
measure: Percentage of participants achieving vIGA-AD of 0 or 1 (on a 5-point scale) with a reduction from Baseline of ≥ 2 Points
timeFrame: At Week 16
measure: Percentage of participants achieving a 50% reduction from Baseline in EASI 50 score
timeFrame: At Week 16
measure: Percentage of participants achieving vIGA-AD of 0 or 1 (on a 5-point scale) with a reduction from Baseline of ≥ 2 Points
timeFrame: At Week 52
measure: Percentage of participants achieving vIGA-AD of 0 or 1 (on a 5-point scale) with a reduction from Baseline of ≥ 2 Points
timeFrame: At Week 160
measure: Percentage of participants achieving an improved (reduced) Patient Oriented Eczema Measure (POEM) of ≥ 4 points from from participants with POEM ≥ 4 at Baseline
timeFrame: At Week 16
measure: 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
timeFrame: At Week 8
measure: Percentage of participants ≥ 4 years of age with a Baseline CDLQI score of >1 achieving a CDLQI score of 0 or 1
timeFrame: At Week 16
measure: Percent change in Scoring Atopic Dermatitis (SCORAD) from Baseline
timeFrame: At Week 16
measure: Use of topical or systemic rescue therapy from Baseline to Week 16
timeFrame: Baseline to Week 16
measure: Number of days on rescue topical corticosteroid or topical calcineurin inhibitor from Baseline to Week 16
timeFrame: Baseline to Week 16
measure: Percentage of participants achieving a EASI 75 response for low dose upadacitinib daily adult equivalent dose
timeFrame: At Week 16
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Applied Research Center Of Arkansas /ID# 268547
state: Arkansas
city: Sacramento
country: United States
facility: Integrative Skin Science and Research /ID# 265108
state: California
city: Boca Raton
country: United States
facility: Clearlyderm Dermatology - West Boca /ID# 266323
state: Florida
city: Coral Gables
country: United States
facility: Pediatric Skin Research /ID# 266308
state: Florida
city: Hialeah
country: United States
facility: Neoclinical Research - Hialeah /ID# 269694
state: Florida
city: Dawsonville
country: United States
facility: Cleaver Medical Group Dermatology /ID# 265099
state: Georgia
city: Savannah
country: United States
facility: Aeroallergy Research Laboratory /ID# 267247
state: Georgia
city: Boise
country: United States
facility: Treasure Valley Medical Research /ID# 266838
state: Idaho
city: Normal
country: United States
facility: Sneeze Wheeze & Itch Associates /ID# 267238
state: Illinois
city: Indianapolis
country: United States
facility: Dawes Fretzin, LLC /ID# 265097
state: Indiana
city: Bowling Green
country: United States
facility: Equity Medical, LLC /ID# 268270
state: Kentucky
city: Lanham
country: United States
facility: Maryland Allergy & Asthma Center /ID# 268032
state: Maryland
city: Rockville
country: United States
facility: DermAssociates - Rockville /ID# 266457
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine - St. Louis /ID# 268545
state: Missouri
city: Omaha
country: United States
facility: Skin Specialists /ID# 266331
state: Nebraska
city: Canal Winchester
country: United States
facility: DOCS Clinical Research - Canal Winchester /ID# 268271
state: Ohio
city: Fairborn
country: United States
facility: Wright State Physicians Health Center /ID# 268841
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina /ID# 265113
state: South Carolina
city: Murfreesboro
country: United States
facility: International Clinical Research - Tennessee /ID# 268548
state: Tennessee
city: Arlington
country: United States
facility: Arlington Research Center, Inc /ID# 266330
state: Texas
city: El Paso
country: United States
facility: 3A Research - East location /ID# 267622
state: Texas
city: Mansfield
country: United States
facility: Prime Clinical Research - Mansfield - East Broad Street /ID# 268042
state: Texas
city: San Antonio
country: United States
facility: Texas Dermatology and Laser Specialists /ID# 267249
state: Texas
city: San Antonio
country: United States
facility: Progressive Clinical Research - San Antonio /ID# 267262
state: Texas
city: South Jordan
country: United States
facility: Jordan Valley Dermatology & Research Center /ID# 267092
state: Utah
city: Morgantown
country: United States
facility: West Virginia University Hospitals /ID# 265114
state: West Virginia
city: Milwaukee
country: United States
facility: Wisconsin Medical Center /ID# 267236
state: Wisconsin
city: Clayton
country: Australia
facility: Monash Health - Monash Medical Centre /ID# 267149
state: Victoria
city: Mitcham
country: Australia
facility: Institute for Skin, Health and Immunity /ID# 266158
state: Victoria
city: Graz
country: Austria
facility: Medizinische Universitaet Graz /ID# 262741
state: Steiermark
city: Salzburg
country: Austria
facility: Landeskrankenhaus Salzburg-Universitaetsklinikum der PMU (LKH) /ID# 265427
city: Wien
country: Austria
facility: Medizinische Universitaet Wien /ID# 265417
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia de Porto Alegre /ID# 267455
state: Rio Grande Do Sul
city: Campinas
country: Brazil
facility: Hospital e Maternidade Celso Pierro - PUC-Campinas /ID# 266965
state: Sao Paulo
city: Ribeirão Preto
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto /ID# 266964
state: Sao Paulo
city: Sorocaba
country: Brazil
facility: Clinica de Alergia Martti Antila /ID# 266197
state: Sao Paulo
city: Pleven
country: Bulgaria
facility: Medical Center Cordis /ID# 265250
city: Sofiya
country: Bulgaria
facility: UMHAT Alexandrovska EAD /ID# 265256
city: Calgary
country: Canada
facility: Dermatology Research Institute - Blackfoot Trail /ID# 266744
state: Alberta
city: Edmonton
country: Canada
facility: Rejuvenation Dermatology - Edmonton Downtown /ID# 267871
state: Alberta
city: Halifax
country: Canada
facility: Maritime Dermatology /ID# 267359
state: Nova Scotia
city: Hamilton
country: Canada
facility: Leader Research /ID# 266745
state: Ontario
city: Hamilton
country: Canada
facility: Triple A Lab Inc /ID# 266615
state: Ontario
city: Markham
country: Canada
facility: Lynde Institute for Dermatology /ID# 267006
state: Ontario
city: Niagara Falls
country: Canada
facility: Allergy Research Canada /ID# 270230
state: Ontario
city: Toronto
country: Canada
facility: DermAtelier on Avenue /ID# 267850
state: Ontario
city: Beijing
country: China
facility: Beijing Children's Hospital /ID# 266350
state: Beijing
city: Xia Men
country: China
facility: Xiamen Children's Hospital /ID# 266384
state: Fujian
city: Zhengzhou
country: China
facility: Henan Children's Hospital Zhengzhou Children's Hospital /ID# 266832
state: Henan
city: Changsha
country: China
facility: Hunan Children's Hospital /ID# 266365
state: Hunan
city: Dalian
country: China
facility: Dalian Medical University - Dalian Children's Hospital /ID# 266675
state: Liaoning
city: Chengdu
country: China
facility: Chengdu Women and Children Center Hospital /ID# 266402
state: Sichuan
city: Kunming
country: China
facility: Kunming Children's Hospital /ID# 266555
state: Yunnan
city: Zagreb
country: Croatia
facility: Klinika za dječje bolesti Zagreb /ID# 264936
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Poliklinika DermaPlus /ID# 265724
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Poliklinika Solmed /ID# 265070
state: Grad Zagreb
city: Split
country: Croatia
facility: Klinicki Bolnicki Centar (KBC) Split /ID# 265359
state: Splitsko-dalmatinska Zupanija
city: Rijeka
country: Croatia
facility: Specialty hospital Medico /ID# 266116
city: Toulouse
country: France
facility: CHU Toulouse - Hopital Larrey /ID# 255048
state: Haute-Garonne
city: Vandœuvre-lès-Nancy
country: France
facility: Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois /ID# 265455
state: Meurthe-et-Moselle
city: Bordeaux
country: France
facility: CHU Bordeaux - Hopital Pellegrin /ID# 266818
state: Nouvelle-Aquitaine
city: Clermont-Ferrand
country: France
facility: Centre Hospitalier Universitaire de Clermont Ferrand - Hopital Estaing /ID# 267327
state: Puy-de-Dome
city: Amiens CEDEX 1
country: France
facility: CHU Amiens-Picardie Site Sud /ID# 255083
state: Somme
city: Argenteuil
country: France
facility: Centre Hospitalier d'Argenteuil Victor Dupouy /ID# 265448
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu /ID# 265449
city: Paris
country: France
facility: AP-HP - Hopital Necker /ID# 255050
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen /ID# 255168
state: Bayern
city: Bad Bentheim
country: Germany
facility: Fachklinik Bad Bentheim /ID# 255165
state: Niedersachsen
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster /ID# 255166
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus Dresden /ID# 255167
state: Sachsen
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin - Campus Mitte /ID# 267411
city: Oroshaza
country: Hungary
facility: DermaMed Research - Oroshaza /ID# 266995
state: Bekes
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont /ID# 265653
state: Csongrad
city: Debrecen
country: Hungary
facility: Debreceni Egyetem-Klinikai Kozpont /ID# 265331
state: Hajdu-Bihar
city: Afula
country: Israel
facility: HaEmek Medical Center /ID# 266416
state: H_efa
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center /ID# 265251
state: HaDarom
city: Petah Tikva
country: Israel
facility: Schneider Childrens Medical Center of Israel /ID# 265617
state: HaMerkaz
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 265254
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Hadassah Medical Center-Hebrew University /ID# 255041
state: Yerushalayim
city: Rome
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico Umberto I /ID# 267070
state: Roma
city: Bologna
country: Italy
facility: IRCCS AOU di Bologna Policlinico Sant Orsola Malpighi /ID# 255118
city: Ansan-si
country: Korea, Republic of
facility: Korea University Ansan Hospital /ID# 264169
state: Gyeonggido
city: Bucheon-si
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Bucheon /ID# 264171
state: Gyeonggido
city: Dongjak-gu
country: Korea, Republic of
facility: Chungang University Hospital /ID# 266383
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 264176
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center /ID# 264178
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Hallym University Kangnam Sacred Heart Hospital /ID# 267318
state: Seoul Teugbyeolsi
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, locatie AMC /ID# 265406
state: Noord-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum /ID# 265408
state: Zuid-Holland
city: Torun
country: Poland
facility: MICS Centrum Medyczne Torun /ID# 265454
state: Kujawsko-pomorskie
city: Krakow
country: Poland
facility: Centrum Nowoczesnych Terapii 'Dobry Lekarz' sp.z.o.o. /ID# 266030
state: Malopolskie
city: Warsaw
country: Poland
facility: Royalderm Agnieszka Nawrocka /ID# 266606
state: Mazowieckie
city: Warszawa
country: Poland
facility: Klinika Osipowicz & Turkowski sp.z.o.o /ID# 267490
state: Mazowieckie
city: Warszawa
country: Poland
facility: Clinical Research Group Sp. z o.o. /ID# 266924
state: Mazowieckie
city: Warszawa
country: Poland
facility: Klinika Ambroziak Dermatologia /ID# 265458
state: Mazowieckie
city: Bialystok
country: Poland
facility: NZOZ Specjalistyczny Osrodek Dermatologiczny Dermal /ID# 266613
state: Podlaskie
city: Gdansk
country: Poland
facility: Centrum Badan Klinicznych PI-House sp. z o.o. /ID# 265451
state: Pomorskie
city: Katowice
country: Poland
facility: Centrum Medyczne Angelius Provita /ID# 265456
state: Slaskie
city: Poznan
country: Poland
facility: Specjalistyczny Niepubliczny Zaklad Opieki Zdrowotnej Alergologia Plus /ID# 265457
state: Wielkopolskie
city: Coimbra
country: Portugal
facility: Unidade Local de Saude de Coimbra, EPE /ID# 266115
city: Porto
country: Portugal
facility: Unidade Local de Saude de Santo Antonio, E.P.E. /ID# 266112
city: Porto
country: Portugal
facility: Unidade Local de Saude de Sao Joao, EPE /ID# 266111
city: Bayamon
country: Puerto Rico
facility: Clinical Research Investigator Group, LLC /ID# 268366
city: Carolina
country: Puerto Rico
facility: Private Practice - Dr. Alma Cruz /ID# 264234
city: Singapore
country: Singapore
facility: National University Hospital /ID# 265685
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital /ID# 266519
city: Bratislava
country: Slovakia
facility: Narodny Ustav Detskych Chorob /ID# 265253
state: Bratislavsky Kraj
city: Kosice
country: Slovakia
facility: ALERSA, s.r.o. /ID# 266245
state: Kosicky Kraj
city: Košice
country: Slovakia
facility: Univerzitna nemocnica L. Pasteura Kosice /ID# 265239
state: Kosicky Kraj
city: Martin
country: Slovakia
facility: Univerzitna nemocnica Martin /ID# 265947
state: Zilinsky Kraj
city: Trnava
country: Slovakia
facility: Fakultna nemocnica Trnava /ID# 265245
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu /ID# 255287
state: Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon /ID# 255288
city: Madrid
country: Spain
facility: Hospital Universitario La Paz /ID# 255286
city: Valencia
country: Spain
facility: Consorci Hospital General Universitario de Valencia /ID# 255289
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet /ID# 255290
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital /ID# 267791
state: Kaohsiung
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 265510
state: Taipei
city: New Taipei City
country: Taiwan
facility: New Taipei Municipal TuCheng Hospital (Built and Operated by Chang Gung Medical /ID# 266349
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital /ID# 265507
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital /ID# 263664
city: Plymouth
country: United Kingdom
facility: Derriford Hospital and the Royal Eye Infirmary /ID# 266980
state: Devon
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital /ID# 266389
state: Greater London
city: London
country: United Kingdom
facility: St. George's Hospital /ID# 266984
state: Greater London
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital /ID# 265219
state: Lanarkshire
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary /ID# 265238
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: