Clinical trial NCT05609630: Study of Oral Upadacitinib and Subcutaneous/Intravenous Tocilizumab to Evaluate Change in Disease Activity, Adverse Events and How Drug Moves Through the Body of Pediatric and Adolescent Participants With Active Systemic Juvenile Idiopathic Arthritis.
Official title: A Multicenter, Randomized Open-Label Study to Assess the Efficacy, Safety, and Pharmacokinetics of Upadacitinib With a Tocilizumab Reference Arm in Subjects From 1 Year to Less Than 18 Years Old With Active Systemic Juvenile Idiopathic Arthritis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Juvenile Idiopathic Arthritis
Keywords: Systemic Juvenile Idiopathic Arthritis
sJIA
Upadacitinib
ABT-494
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2022-11-08
Enrollment: 90
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Juvenile Idiopathic Arthritis (JIA) is the most common type of arthritis that affects children. The term "idiopathic" means "of unknown origin". It is a chronic (long-lasting) disease that causes swelling, warmth, and pain of one or more small joints. Systemic JIA ia a rare and serious form of JIA. Systemic" means it may affect not only the joints but other parts of the body, including the liver, lungs and heart. sJIA is more severe and can be more challenging to diagnose and treat than other types of juvenile idiopathic arthritis. It is a lifelong disease for many patients and can continue into adulthood. This study will assess how safe and effective upadacitinib is in treating pediatric and adolescent participants aged 1 to \< 18 with systemic juvenile idiopathic arthritis (sJIA) and will include a tocilizumab treatment arm for reference. Adverse events and change in the disease activity will be assessed.

Upadacitinib is an investigational drug being developed for the treatment of sJIA. Participants are assigned to 1 of 2 cohorts. In cohort 1, participants will receive upadacitinib or tocilizumab reference. In cohort 2, participants will receive upadacitinib. Approximately 90 participants with sJIA will be enrolled in approximately 45 sites worldwide.

Participants will receive upadacitinib oral tablets once daily or oral solution twice daily or tocilizumab subcutaneous injection or intravenous infusion as per local label for 52 weeks and followed for approximately 30 days.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits/calls during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, checking for side effects and completing questionnaires.


Eligibility criteria: Inclusion Criteria:

- Baseline with a total body weight of 10 kg or higher at screening and symptoms of systemic juvenile idiopathic arthritis (sJIA) according to International League of Associations for Rheumatology (ILAR) criteria for at least 6 weeks prior to Screening, with onset prior to 16 years old, and meet the following conditions:

* Must have active sJIA with at least 2 active joints at Screening and Baseline, fever more than 38°C on at least one day within 14 consecutive days before the Screening Visit, and an erythrocyte sedimentation rate (ESR) or high-sensitivity C-reactive protein (hsCRP) \> upper limit of normal (ULN) at Screening. OR At least 4 active joints at Screening and Baseline and an ESR or hsCRP \> ULN at Screening.
* Must have inadequate response to previous treatment with nonsteroidal anti-inflammatory drugs and/or systemic glucocorticoids, as judged by the investigator.
* For Cohort 1, participants must not have had previous treatment with any IL-6 inhibitor. For Cohort 2, participants must have an intolerance or inadequate response to an IL-6 inhibitor as judged by the investigator.

Note: For Cohort 1, participants must be ages 2 to \< 18 years old in countries where SC tocilizumab is not approved for sJIA.

Exclusion Criteria:

* Has any type of juvenile idiopathic arthritis (JIA), other than sJIA, as defined by the ILAR criteria, and must not have a history or presence of any other autoimmune inflammatory condition other than sJIA.
* Has uncontrolled severe systemic disease and/or impeding or active macrophage activation syndrome within 1 month prior to Baseline.

Primary outcomes:
measure: Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 30 Response
timeFrame: At Week 12
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to Approximately Week 52
Secondary outcomes:
measure: Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 50 Response
timeFrame: Week 12
measure: Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 70 Response
timeFrame: Week 12
measure: Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 90 Response
timeFrame: Week 12
measure: Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 100 Response
timeFrame: Week 12
measure: Change from Baseline in Number of Joints with Active Arthritis
timeFrame: Week 12
measure: Change from Baseline in Number of Joints with Limitation of Motion
timeFrame: Week 12
measure: Change from Baseline in Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI)
timeFrame: Week 12
measure: Change From Baseline in Patient's Global Assessment (PtGA)
timeFrame: Week 12
measure: Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA)
timeFrame: Week 12
measure: Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)
timeFrame: Week 12
measure: Percentage of Participants with Absence of fever (> 38°C) Attributed to systemic Juvenile Idiopathic Arthritis (sJIA)
timeFrame: Week 12
measure: Change from Baseline in Glucocorticoid Dose
timeFrame: Week 12
measure: Change from Baseline in Juvenile Arthritis Disease Activity Score (JADAS27-CRP)
timeFrame: Week 12
measure: Percentage of Participants Achieving Inactive Disease (ID) Status by Juvenile Arthritis Disease Activity Score (JADAS27)-CRP
timeFrame: Week 12
measure: Percentage of Participants Achieving Minimal Disease Activity (MDA) by Juvenile Arthritis Disease Activity Score (JADAS27)-CRP
timeFrame: Week 12
measure: Percentage of Participants Achieving Clinical Remission by Juvenile Arthritis Disease Activity Score (JADAS27)-CRP
timeFrame: Week 12
Other outcomes:
Locations:
city: Valhalla
country: United States
facility: New York Medical College /ID# 253437
state: New York
city: Charlotte
country: United States
facility: Levine Children's Hospital /ID# 253491
state: North Carolina
city: Portland
country: United States
facility: Randall Children's Hospital /ID# 251829
state: Oregon
city: Clayton
country: Australia
facility: Monash Health - Monash Medical Centre /ID# 251691
state: Victoria
city: Parkville
country: Australia
facility: Royal Children's Hospital /ID# 251663
state: Victoria
city: Bregenz
country: Austria
facility: Landeskrankenhaus Bregenz /ID# 266317
state: Vorarlberg
city: Juiz de Fora
country: Brazil
facility: CMiP - Centro Mineiro de Pesquisa Ltda - ME /ID# 251769
state: Minas Gerais
city: Sao Paulo
country: Brazil
facility: Hospital Sao Paulo /ID# 251765
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao /ID# 251764
city: Chongqing
country: China
facility: The Children's Hospital of Chongqing Medical University /ID# 251539
state: Chongqing
city: Suzhou
country: China
facility: Children'S Hospital Of Soochow University /ID# 251755
state: Jiangsu
city: Xi'an
country: China
facility: Xi'an Children's Hospital /ID# 251693
state: Shaanxi
city: Shanghai
country: China
facility: Children's Hospital of Fudan University /ID# 251619
state: Shanghai
city: Hangzhou
country: China
facility: The Children's Hospital of Zhejiang University School of Medicine /ID# 251754
state: Zhejiang
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg /ID# 253288
state: Baden-Wuerttemberg
city: Sankt Augustin
country: Germany
facility: Asklepios Klinik Sankt Augustin /ID# 251565
state: Nordrhein-Westfalen
city: Sendenhorst
country: Germany
facility: St. Josef-Stift Sendenhorst /ID# 268680
state: Nordrhein-Westfalen
city: Hamburg
country: Germany
facility: Hamburger Zentrum fuer Kinder- und Jugendrheumatologie /ID# 251564
city: Budapest
country: Hungary
facility: Semmelweis Egyetem /ID# 266750
city: Florence
country: Italy
facility: Azienda Ospedaliero Universitaria Meyer /ID# 251775
state: Firenze
city: Genoa
country: Italy
facility: IRCCS Istituto Giannina Gaslini /ID# 251776
state: Genova
city: Kobe-shi
country: Japan
facility: Hyogo Prefectural Kobe Children's Hospital /ID# 251649
state: Hyogo
city: Kawasaki-shi
country: Japan
facility: St. Marianna University Hospital /ID# 251623
state: Kanagawa
city: Niigata-shi
country: Japan
facility: Niigata University Medical & Dental Hospital /ID# 251538
state: Niigata
city: Takatsuki-shi
country: Japan
facility: Osaka Medical and Pharmaceutical University Hospital /ID# 252092
state: Osaka
city: Bunkyo-ku
country: Japan
facility: Institute of Science Tokyo Hospital /ID# 251505
state: Tokyo
city: Guadalajara
country: Mexico
facility: CREA de Guadalajara SC /ID# 252917
state: Jalisco
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht /ID# 267435
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu /ID# 251353
state: Barcelona
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe /ID# 251352
city: Gothenburg
country: Sweden
facility: Queen Silvia Children's Hosp /ID# 251318
state: Vastra Gotalands Lan
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 267387
state: Taipei
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital /ID# 267390
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty /ID# 253677
city: Istanbul
country: Turkey
facility: Istanbul University Istanbul Medical Faculty /ID# 251652
city: Istanbul
country: Turkey
facility: Istanbul Universitesi-Cerrahpasa Cerrahpasa Tip Fakultesi /ID# 251651
city: Istanbul
country: Turkey
facility: Umraniye Training and Res Hosp /ID# 251653
city: London
country: United Kingdom
facility: Great Ormond Street Children's Hospital /ID# 251512
state: Greater London
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: