This study is an open-label, randomized, multicenter trial that incorporates a multi-arm design comparing each of 3 non-TNFi (Tumor Necrosis Factor inhibitor) medications to a second TNFi (active control) within a sequential multiple assignment randomized trial design with 2 randomization stages corresponding with clinical decision points. The first randomization addresses whether each of the 3 non-TNFi medications is superior to treatment with a second TNFi. The second randomization allows identification of optimal sequential use of biologics (treatment strategies).
The goal of the study is to provide an evidence base for selecting sequential medication(s) if a JIA patient fails initial bDMARD. SMART-JIA is a pragmatic, international, open-label, randomized trial comparing treatment with a second TNFi (active control) to each of 3 different medications (IL-6i, JAKi, or ABA) in children aged 2 to 17 years with pcJIA and inadequate response to initial TNFi. Leveraging sequential multiple assignment randomized trial (SMART) design methodology, we will implement a second randomization to assess the effectiveness of changing medication if there is inadequate response to the first study medication. This approach allows identification of optimal strategies for medication sequencing based on individual characteristics and provides critical insights to inform future studies. SMART-JIA will study the efficacy of a second TNFi (active control) compared to each of 3 other already US Food and Drug Administration (FDA)-approved and European Union (EU)-approved non-TNFi medications currently used to treat pcJIA (IL-6i, JAKi, and ABA). TNFi, IL-6i, and ABA are administered by subcutaneous (SQ) injection weekly, or every other week, or every three weeks, and JAKi (e.g., tofacitinib) is taken orally twice daily. All study treatments have similar safety profiles and are standard of care (SOC) worldwide. This in addition to the pragmatic and full-scale nature of the trial will ensure its completion. Successful completion of this trial will substantially impact the clinical care and outcomes of children with pcJIA, shifting the current trial-and-error treatment paradigm to a smart, precise approach.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
400
Adalimumab 10 kg (22 lbs) to \<15 kg (33 lbs) 10 mg every other week\* 15 kg (33 lbs) to \<30 kg (66 lbs) 20 mg every other week ≥30 kg (66 lbs) 40 mg every other week Etanercept ≥63 kg (138 lb) 50 mg weekly \<63 kg (138 lb) 0.8 mg/kg weekly
10 kg to \<25 kg 50 mg once weekly 25 kg to \<50 kg 87.5 mg once weekly ≥50 kg 125 mg once weekly
\<30 kg 162 mg once every 3 weeks ≥30 kg 162 mg once every 2 weeks
10 to \<20 kg 3.2 mg (3.2 mL oral solution) BID 20 to \<40 kg 4 mg (4 mL oral solution) BID ≥40 kg 5 mg (one 5 mg tablet or 5 mL oral solution) BID
Number of participants with MiDA
Minimal disease activity (MiDA) at Month 6 as assessed by the cJADAS10 ≤5 MiDA is low-disease activity and inactive disease in this protocol. Score range for the cJADAS10 (total): 0 - 30. Disease State cJADAS10 Score Inactive disease ≤2.5 Low-disease activity 2.6 - 5 Moderate-disease activity 5.1 - 16 High-disease activity \>16 Minimal disease activity (MiDA) is a state of low disease activity or remission that is considered a useful treatment target for both patients and physicians. The clinical Juvenile Arthritis Disease Activity Score (cJADAS10) is a tool used to measure the level of disease activity in non-systemic juvenile idiopathic arthritis (JIA). It's a composite index that combines information from several sources, including: * The number of active joints, up to 10 * The physician's global assessment of disease activity (PhGA) * The patient or parental global assessment of well-being (PaGA)
Time frame: Month 6
PROMIS® Pain Interference at Month 6
Patient-Reported Outcomes Measurement Information System (PROMIS). For most PROMIS instruments, a score of 50 is the average for the United States general population with a standard deviation of 10 because calibration testing was performed on a large sample of the general population. For PROMIS measures, higher scores equals more of the concept being measured (e.g., more Fatigue, more Physical Function). Thus a score of 60 is one standard deviation above the average referenced population. This could be a desirable or undesirable outcome, depending upon the concept being measured.
Time frame: Month 6
PROMIS® Fatigue at Month 6
Patient-Reported Outcomes Measurement Information System (PROMIS). For most PROMIS instruments, a score of 50 is the average for the United States general population with a standard deviation of 10 because calibration testing was performed on a large sample of the general population. For PROMIS measures, higher scores equals more of the concept being measured (e.g., more Fatigue, more Physical Function). Thus a score of 60 is one standard deviation above the average referenced population. This could be a desirable or undesirable outcome, depending upon the concept being measured.
Time frame: Month 6
PROMIS® Physical Function at Month 6
Patient-Reported Outcomes Measurement Information System (PROMIS). For most PROMIS instruments, a score of 50 is the average for the United States general population with a standard deviation of 10 because calibration testing was performed on a large sample of the general population. For PROMIS measures, higher scores equals more of the concept being measured (e.g., more Fatigue, more Physical Function). Thus a score of 60 is one standard deviation above the average referenced population. This could be a desirable or undesirable outcome, depending upon the concept being measured.
Time frame: Month 6
Change in arthritis disease activity (cJADAS10)
Minimal disease activity (MiDA) at Month 6 as assessed by the cJADAS10 ≤5 MiDA is low-disease activity and inactive disease in this protocol. Score range for the cJADAS10 (total): 0 - 30. Disease State cJADAS10 Score Inactive disease ≤2.5 Low-disease activity 2.6 - 5 Moderate-disease activity 5.1 - 16 High-disease activity \>16 Minimal disease activity (MiDA) is a state of low disease activity or remission that is considered a useful treatment target for both patients and physicians.
Time frame: Month 6
Change in arthritis disease activity (JIA American College of Rheumatology Pediatric 70 [ACR 70]) at Month 6
The ACR score is a scale to measure change in rheumatoid arthritis symptoms. An ACR70 response represents at least a 70% improvement in tender and swollen joint counts.
Time frame: Month 6
Number of participants with MiDA (Change in arthritis disease activity [cJADAS10] at Month 12)
Minimal disease activity (MiDA) at Month 12 as assessed by the cJADAS10 ≤5 MiDA is low-disease activity and inactive disease in this protocol. Score range for the cJADAS10 (total): 0 - 30. Disease State cJADAS10 Score Inactive disease ≤2.5 Low-disease activity 2.6 - 5 Moderate-disease activity 5.1 - 16 High-disease activity \>16 Minimal disease activity (MiDA) is a state of low disease activity or remission that is considered a useful treatment target for both patients and physicians.
Time frame: Month 12
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