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.

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

\- 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 6 центров

• 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

Китай · 5 центров

• The Childrens Hospital of Chongqing Medical University /ID# 251539 — Чунцин
• Children'S Hospital Of Soochow University /ID# 251755 — Сучжоу
• Xi'an Children's Hospital /ID# 251693 — Сиань
• Children's Hospital of Fudan University /ID# 251619 — Шанхай
• The Children's Hospital of Zhejiang University School of Medicine /ID# 251754 — Ханчжоу

Япония · 5 центров

• 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

Германия · 4 центра

• 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

Швеция · 4 центра

• 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 центра

• 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

Аргентина · 3 центра

• 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

Бразилия · 3 центра

• 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

Австралия · 2 центра

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

Италия · 2 центра

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

Испания · 2 центра

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

Тайвань · 2 центра

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

Австрия · 1 центр

• Landeskrankenhaus Bregenz /ID# 266317 — Bregenz

Венгрия · 1 центр

• Semmelweis Egyetem /ID# 266750 — Budapest

Мексика · 1 центр

• CREA de Guadalajara SC /ID# 252917 — Guadalajara

Нидерланды · 1 центр

• Universitair Medisch Centrum Utrecht /ID# 267435 — Utrecht

Великобритания · 1 центр

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

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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