About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Polyarticular course JIA

Moderate or high-disease activity (cJADAS10 >5) despite treatment with an initial TNFi for ≥2 months

Age ≥2 years and <21 years and weight ≥ 10kg

No systemic glucocorticoids or systemic glucocorticoids at a stable dose of ≤0.2 mg/kg/day (maximum 10 mg/day) for ≥2 weeks prior to baseline visit

Disqualifiers

Systemic JIA

Enthesitis-related arthritis/juvenile spondyloarthritis (2001 International League of Associations for Rheumatology [ILAR] criteria)30

History of or currently active inflammatory bowel disease

History of or currently active psoriasis

Trial design

Design model

Sequential

Treatments tested in this trial

TNFi (Tumor Necrosis Factor inhibitor) medication
Drug
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
Abatacept
Drug
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
Tocilizumab
Drug
\<30 kg 162 mg once every 3 weeks ≥30 kg 162 mg once every 2 weeks
Tofacitinib
Drug
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

Treatment groups

400 Participants

are divided into 4 treatment groups

Group A: Second TNFi (Tumor Necrosis Factor inhibitor) medicationActive comparator 1 intervention

Group B: AbataceptActive comparator 1 intervention

Group C: Tocilizumab originator or biosimilarActive comparator 1 intervention

Group D: TofacitinibActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

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

Secondary outcomes

1

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

2

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

3

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

4

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