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.

Sponsor

AbbVie (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05609630

Collaborator

(none)

Enrollment

Arms

69.6

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Juvenile Idiopathic Arthritis	Drug: Upadacitinib Drug: Tocilizumab	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Mar 15, 2023

Anticipated Primary Completion Date :

Oct 15, 2026

Anticipated Study Completion Date :

Dec 31, 2028

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 30 Response [At Week 12]
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%.

Secondary Outcome Measures

Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 50 Response [Week 12]
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.
Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 70 Response [Week 12]
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.
Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 90 Response [Week 12]
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.
Percentage of Participants Achieving Adapted systemic Juvenile Idiopathic Arthritis (sJIA) American College of Rheumatology (ACR) 100 Response [Week 12]
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.
Change from Baseline in Number of Joints with Active Arthritis [Week 12]
Change from Baseline in Number of Joints with Active Arthritis
Change from Baseline in Number of Joints with Limitation of Motion [Week 12]
Change from Baseline in Number of Joints with Limitation of Motion
Change from Baseline in Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI) [Week 12]
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.
Change From Baseline in Patient's Global Assessment (PtGA) [Week 12]
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.
Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) [Week 12]
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.
Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP) [Week 12]
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.
Percentage of Participants with Absence of fever (> 38°C) Attributed to systemic Juvenile Idiopathic Arthritis (sJIA) [Week 12]
Absence of fever (> 38°C) Attributed to systemic Juvenile Idiopathic Arthritis (sJIA)
Change from Baseline in Glucocorticoid Dose [Week 12]
Change from Baseline in Glucocorticoid Dose
Change from Baseline in Juvenile Arthritis Disease Activity Score (JADAS27-CRP) [Week 12]
Juvenile Arthritis Disease Activity Score (JADAS27-CRP) will be assessed
Percentage of Participants Achieving Inactive Disease (ID) Status by Juvenile Arthritis Disease Activity Score (JADAS27)-CRP [Week 12]
Inactive Disease (ID) status by 27-joint Juvenile Arthritis Disease Activity Score (JADAS27)-CRP will be assessed.
Percentage of Participants Achieving Minimal Disease Activity (MDA) by Juvenile Arthritis Disease Activity Score (JADAS27)-CRP [Week 12]
Minimal Disease Activity (MDA) by 27-joint Juvenile Arthritis Disease Activity Score (JADAS27)-CRP will be assessed.
Percentage of Participants Achieving Clinical Remission by Juvenile Arthritis Disease Activity Score (JADAS27)-CRP [Week 12]
Clinical Remission by 27-joint Juvenile Arthritis Disease Activity Score (JADAS27)-CRP will be assessed.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.