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.
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.
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.
Parallel
Upadacitinib
DrugOral tablet or Oral solution
Tocilizumab
DrugSubcutaneous injection or Intravenous infusion
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%.
Number of Participants with Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
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.
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.
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.
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.
