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

Overview

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.

Interventions

• Drug Upadacitinib
  Oral tablet or Oral solution
• Drug Tocilizumab
  Subcutaneous injection or Intravenous infusion

Primary outcome measures

• Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 30 Response [Time frame: At Week 12]
• Number of Participants with Adverse Events (AEs) [Time frame: Up to Approximately Week 52]

Secondary outcome measures (12)

• Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 50 Response [Time frame: Week 12]
• Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 70 Response [Time frame: Week 12]
• Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 90 Response [Time frame: Week 12]
• Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 100 Response [Time frame: Week 12]
• Change from Baseline in Number of Joints with Active Arthritis [Time frame: Week 12]
• Change from Baseline in Number of Joints with Limitation of Motion [Time frame: Week 12]
• Change from Baseline in Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) [Time frame: Week 12]
• Change From Baseline in Patient's Global Assessment (PtGA) [Time frame: Week 12]
• Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) [Time frame: Week 12]
• Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) [Time frame: Week 12]
• Percentage of Participants with Absence of fever (> 38°C) Attributed to systemic Juvenile Idiopathic Arthritis (sJIA) [Time frame: Week 12]
• Change from Baseline in Glucocorticoid Dose [Time frame: Week 12]

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.

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

Open label

Primary purpose

Treatment

Study locations

United States · 6 centers

• Phoenix Children's Hospital /ID# 253403 — Phoenix
• Childrens National Medical Center /ID# 253344 — Washington D.C.
• New York Medical College /ID# 253437 — Valhalla
• Levine Children's Hospital /ID# 253491 — Charlotte
• Cincinnati Childrens Hospital Medical Center /ID# 251827 — Cincinnati
• Randall Children's Hospital /ID# 251829 — Portland

China · 5 centers

• The Childrens Hospital of Chongqing Medical University /ID# 251539 — Chongqing
• Children'S Hospital Of Soochow University /ID# 251755 — Suzhou
• Xi'an Children's Hospital /ID# 251693 — Xi'an
• Children's Hospital of Fudan University /ID# 251619 — Shanghai
• The Children's Hospital of Zhejiang University School of Medicine /ID# 251754 — Hangzhou

Japan · 5 centers

• Hyogo Prefectural Kobe Children'S Hospital - Minatojima /ID# 251649 — Kobe
• St Marianna University School Of Medicine /ID# 251623 — Kawasaki-shi
• Niigata University Medical and Dental Hospital /ID# 251538 — Niigata
• Osaka Medical and Pharmaceutical University Hospital /ID# 252092 — Takatsuki-shi
• Institute of Science Tokyo Hospital /ID# 251505 — Bunkyo-ku

Germany · 4 centers

• Universitaetsklinikum Freiburg /ID# 253288 — Freiburg im Breisgau
• Asklepios Klinik Sankt Augustin /ID# 251565 — Sankt Augustin
• St. Josef-Stift Sendenhorst /ID# 268680 — Sendenhorst
• Hamburger Zentrum fuer Kinder- und Jugendrheumatologie /ID# 251564 — Hamburg

Sweden · 4 centers

• Ostersunds Sjukhus /ID# 281645 — Östersund
• Skane University Hospital Lund /ID# 282573 — Lund
• Akademiska Sjukhuset - Uppsala University Hospital /ID# 282653 — Uppsala
• Queen Silvia Children's Hosp /ID# 251318 — Gothenburg

Turkey (Türkiye) · 4 centers

• Gazi University Medical Faculty /ID# 253677 — Ankara
• Istanbul University Istanbul Medical Faculty /ID# 251652 — Istanbul
• Istanbul Universitesi-Cerrahpasa Cerrahpasa Tip Fakultesi /ID# 251651 — Istanbul
• Umraniye Training and Res Hosp /ID# 251653 — Istanbul

Argentina · 3 centers

• Instituto CAICI S.R.L /ID# 251448 — Rosario
• Centro de Investigaciones Medicas Tucuman /ID# 251781 — San Miguel de Tucumán
• Hospital de Niños de la Santisima Trinidad /ID# 252736 — Córdoba

Brazil · 3 centers

• CMiP - Centro Mineiro de Pesquisa Ltda - ME /ID# 251769 — Juiz de Fora
• Hospital Sao Paulo /ID# 251765 — São Paulo
• Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao /ID# 251764 — São Paulo

Australia · 2 centers

• Monash Health - Monash Medical Centre - Clayton /ID# 251691 — Clayton
• Royal Children's Hospital /ID# 251663 — Parkville

Italy · 2 centers

• Azienda Ospedaliero Universitaria Meyer /ID# 251775 — Florence
• IRCCS Istituto Giannina Gaslini /ID# 251776 — Genoa

Spain · 2 centers

• Hospital Sant Joan de Deu /ID# 251353 — Esplugues de Llobregat
• Hospital Universitario y Politecnico La Fe /ID# 251352 — Valencia

Taiwan · 2 centers

• National Taiwan University Hospital /ID# 267387 — Taipei
• Linkou Chang Gung Memorial Hospital /ID# 267390 — Taoyuan City

Austria · 1 center

• Landeskrankenhaus Bregenz /ID# 266317 — Bregenz

Hungary · 1 center

• Semmelweis Egyetem /ID# 266750 — Budapest

Mexico · 1 center

• CREA de Guadalajara SC /ID# 252917 — Guadalajara

Netherlands · 1 center

• Universitair Medisch Centrum Utrecht /ID# 267435 — Utrecht

United Kingdom · 1 center

• Great Ormond Street Children's Hospital /ID# 251512 — London

Identifiers

NCT: NCT05609630 · M14-682 · 2022-501599-25-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗