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.

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Juvenile Idiopathic Arthritis

Intervention / Treatment
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* Drug: Upadacitinib
* Drug: Tocilizumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Upadacitinib, Systemic Juvenile Idiopathic Arthritis, sJIA, ABT-494