Trial of Sequential Medications AfteR TNFi Failure in Juvenile Idiopathic Arthritis

Summary

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

Inclusion Criteria:

* Polyarticular course JIA
* Moderate or high-disease activity (cJADAS10 \>5) despite treatment with an initial TNFi for ≥3 months
* Age ≥2 years and \<18 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
* Documented informed consent/assent obtained from the parent/caregiver/patient

Exclusion Criteria:

* 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
* Active uveitis within 3 months of the baseline visit
* History of or currently active sacroiliitis
* History of or current malignancy
* Active tuberculosis (TB) or a history of incompletely treated TB; Purified Protein derivative (PPD) or QuantiFERON-TB positive patients (without active TB) unless it is documented that the patient has been adequately treated for TB and can start treatment with a biologic agent, based on the medical judgment of the site investigator and/or an infectious disease specialist; suspected extrapulmonary TB infection; or at high risk of contracting TB, such as close contact with individual with active or latent TB
* Prior treatment with more than one TNFi molecule; exposure to more than one biosimilar of the same TNFi molecule is allowed
* Prior treatment with non-TNFi bDMARDs and/or any JAKi
* Aspartate aminotransferase (AST) or alanine transaminase (ALT) ≥3 × upper limit of normal (ULN) for age and sex
* Serum creatinine \>1.5 × ULN for age and sex
* Platelet count \<150 × 103/μL (\<150,000/mm3)
* Hemoglobin \<7.0 g/dL (\<4.3 mmol/L)
* White blood cell (WBC) count \<3,000/mm3 (\<3.0 × 109/L)
* Neutrophil count \<1,500/mm3 (\<1.5 × 109/L)
* Any active acute, subacute, chronic, or recurrent bacterial, viral, or systemic fungal infection or any major episode of infection requiring hospitalization or treatment during screening or treatment with IV antibiotics completed within 4 weeks of the screening visit or oral antibiotics completed within 2 weeks of the screening visit
* Any medical history that may be considered a contraindication/safety concern with the use of adalimumab, etanercept, tofacitinib, ABA, or an IL-6 inhibitor or their biosimilars, in the opinion of the site investigator

Conditions2

Locations4 sites

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