RecruitingPhase 3NCT06654882

Trial of Sequential Medications AfteR TNFi Failure in Juvenile Idiopathic Arthritis


Sponsor

Duke University

Enrollment

400 participants

Start Date

Jan 9, 2026

Study Type

INTERVENTIONAL

Conditions

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

Min Age: 2 YearsMax Age: 17 Years

Inclusion Criteria5

  • 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 Criteria18

  • 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

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Interventions

DRUGTNFi (Tumor Necrosis Factor inhibitor) medication

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

DRUGAbatacept

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

DRUGTocilizumab

\<30 kg 162 mg once every 3 weeks ≥30 kg 162 mg once every 2 weeks

DRUGTofacitinib

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


Locations(5)

University of California San Francisco Pediatric Rheumatology

San Francisco, California, United States

University of Florida

Gainesville, Florida, United States

Hackensack University Medical Center - Joseph M. Sanzari Children's Hospital

Hackensack, New Jersey, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Asklepios Children's Hospital

Sankt Augustin, North Rhine-Westphalia, Germany

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NCT06654882