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. (SELECT-sJIA)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Juvenile Idiopathic Arthritis
• Intervention / Treatment: Drug: Upadacitinib; Drug: Tocilizumab

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Study Locations

• Australia
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Medical Centre /ID# 251691
    • Parkville, Victoria, Australia, 3052
      • Recruiting
      • Royal Children's Hospital /ID# 251663
• Brazil
  • Sao Paulo, Brazil, 05403-000
    • Recruiting
    • Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao /ID# 251764
• China
  • Chongqing
    • Chongqing, Chongqing, China, 400065
      • Recruiting
      • The Children's Hospital of Chongqing Medical University /ID# 251539
  • Jiangsu
    • Suzhou, Jiangsu, China, 215025
      • Recruiting
      • Children's Hospital of Soochow University /ID# 251755
  • Shaanxi
    • Xi'an, Shaanxi, China, 710054
      • Recruiting
      • Xi'an Children's Hospital /ID# 251693
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Children's Hospital of Fudan University /ID# 251619
• Germany
  • Hamburg, Germany, 22081
    • Recruiting
    • Hamburger Zentrum fuer Kinder- und Jugendrheumatologie /ID# 251564
  • Sankt Augustin, Germany, 53757
    • Recruiting
    • Asklepios Klinik Sankt Augustin /ID# 251565
• Italy
  • Firenze
    • Florence, Firenze, Italy, 50139
      • Recruiting
      • Azienda Ospedaliero Universitaria Meyer /ID# 251775
• Japan
  • Hyogo
    • Kobe-shi, Hyogo, Japan, 650-0047
      • Recruiting
      • Hyogo Prefectural Kobe Children's Hospital /ID# 251649
      • Contact: Site Coordinator; Phone Number: +81-78-945-7300
  • Kanagawa
    • Kawasaki-shi, Kanagawa, Japan, 216-8511
      • Recruiting
      • St. Marianna University Hospital /ID# 251623
  • Niigata
    • Niigata-shi, Niigata, Japan, 951-8520
      • Recruiting
      • Niigata University Medical & Dental Hospital /ID# 251538
  • Osaka
    • Takatsuki-shi, Osaka, Japan, 569-8686
      • Recruiting
      • Osaka Medical and Pharmaceutical University Hospital /ID# 252092
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8519
      • Recruiting
      • Tokyo Medical And Dental University Hospital /ID# 251505
• Spain
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitario y Politecnico La Fe /ID# 251352
• Turkey
  • Ankara, Turkey, 06560
    • Recruiting
    • Gazi University Medical Faculty /ID# 253677
  • Istanbul, Turkey, 34093
    • Recruiting
    • Istanbul University Istanbul Medical Faculty /ID# 251652
  • Istanbul, Turkey, 34098
    • Recruiting
    • Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty /ID# 251651
• United States
  • Oregon
    • Portland, Oregon, United States, 97227-1654
      • Recruiting
      • Randall Children's Hospital /ID# 251829
      • Contact: Site Coordinator; Phone Number: 1-503-413-2150

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 15 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- Baseline with a total body weight of 10 kg or higher at screening and a diagnosis 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 for any out of 14 consecutive days before the Screening Visit, and an erythrocyte sedimentation rate (ESR) or high-sensitivity C-reactive protein (hsCRP) > 1.5 × upper limit of normal (ULN) at Screening. OR At least 5 active joints at Screening and Baseline and an ESR or hsCRP > 1.5 × ULN at Screening.
• Must have inadequate response to previous treatment with nonsteroidal anti-inflammatory drugs and 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:

• Must have 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.
• Must have uncontrolled severe systemic disease and/or impeding or active macrophage activation syndrome within 3 months prior to Baseline.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 Upadacitinib; Participants will receive upadacitinib for 52 weeks.	Drug: Upadacitinib; Oral tablet or Oral solution; Other Names: RINVOQ; ABT-494
Active Comparator: Cohort 1 Tocilizumab; Participants will receive tocilizumab for 52 weeks.	Drug: Tocilizumab; Subcutaneous injection or Intravenous infusion
Experimental: Cohort 2 Upadacitinib; Participants will receive upadacitinib for 52 weeks.	Drug: Upadacitinib; Oral tablet or Oral solution; Other Names: RINVOQ; ABT-494

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 30 Response	ACR criteria measure improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant. ACR 30 Response is defined as absence of fever [> 38°C] in the previous 1 week preceding evaluation and improvement of ≥ 30% of the 6 variables of the JIA core set with no more than 1 variable worsening by > 30%.	At Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 50 Response	ACR criteria measure improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant. ACR 50 Response is defined as absence of fever [> 38°C] in the previous 1 week preceding evaluation and improvement of ≥ 50% of the 6 variables of the JIA core set.	Week 12
Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 70 Response	ACR criteria measure improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant. ACR 70 Response is defined as absence of fever [> 38°C] in the previous 1 week preceding evaluation and improvement of ≥ 70% of the 6 variables of the JIA core set.	Week 12
Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 90 Response	ACR criteria measure improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant. ACR 90 Response is defined as absence of fever [> 38°C] in the previous 1 week preceding evaluation and improvement of ≥ 90% of the 6 variables of the JIA core set.	Week 12
Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 100 Response	ACR criteria measure improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant. ACR 100 Response is defined as absence of fever [> 38°C] in the previous 1 week preceding evaluation and improvement of ≥ 100% of the 6 variables of the JIA core set.	Week 12
Change from Baseline in Number of Joints with Active Arthritis	Change from Baseline in Number of Joints with Active Arthritis	Week 12
Change from Baseline in Number of Joints with Limitation of Motion	Change from Baseline in Number of Joints with Limitation of Motion	Week 12
Change from Baseline in Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI)	The CHAQ-DI consists of 30 items and assesses function in 8 areas: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities. There are 5 response options ranging from no difficulty to unable to do, scored 0 to 3, and not applicable.	Week 12
Change From Baseline in Patient's Global Assessment (PtGA)	Participants rated their disease activity for the past 24 hours using a Patient's Global Assessment of Disease Activity Global visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline.	Week 12
Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA)	Participants rated their disease activity for the past 24 hours using a Patient's Global Assessment of Disease Activity Global visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline.	Week 12
Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)	High sensitivity C-reactive protein was analyzed by a central laboratory. The median percent change from baseline in CRP is assessed at each time point.	Week 12
Percentage of Participants with Absence of fever (> 38°C) Attributed to systemic Juvenile Idiopathic Arthritis (sJIA)	Absence of fever (> 38°C) Attributed to systemic Juvenile Idiopathic Arthritis (sJIA)	Week 12
Change from Baseline in Glucocorticoid Dose	Change from Baseline in Glucocorticoid Dose	Week 12
Change from Baseline in Juvenile Arthritis Disease Activity Score (JADAS27-CRP)	Juvenile Arthritis Disease Activity Score (JADAS27-CRP) will be assessed	Week 12
Percentage of Participants Achieving Inactive Disease (ID) Status by Juvenile Arthritis Disease Activity Score (JADAS27)-CRP	Inactive Disease (ID) status by 27-joint Juvenile Arthritis Disease Activity Score (JADAS27)-CRP will be assessed.	Week 12
Percentage of Participants Achieving Minimal Disease Activity (MDA) by Juvenile Arthritis Disease Activity Score (JADAS27)-CRP	Minimal Disease Activity (MDA) by 27-joint Juvenile Arthritis Disease Activity Score (JADAS27)-CRP will be assessed.	Week 12
Percentage of Participants Achieving Clinical Remission by Juvenile Arthritis Disease Activity Score (JADAS27)-CRP	Clinical Remission by 27-joint Juvenile Arthritis Disease Activity Score (JADAS27)-CRP will be assessed.	Week 12

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related info

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2023
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): June 19, 2029

Study Registration Dates

• First Submitted: November 7, 2022
• First Submitted That Met QC Criteria: November 7, 2022
• First Posted (Actual): November 8, 2022

Study Record Updates

• Last Update Posted (Actual): May 13, 2024
• Last Update Submitted That Met QC Criteria: May 9, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Upadacitinib; sJIA; ABT-494; Systemic Juvenile Idiopathic Arthritis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Juvenile; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; Janus Kinase Inhibitors; Upadacitinib
• Other Study ID Numbers: M14-682; 2022-501599-25-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes