Trial of Sequential Medications AfteR TNFi Failure in Juvenile Idiopathic Arthritis

NCT06654882 | Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: Pro00115808PLACER-2022C3-30331EPM #8533
• Study Type: interventional
• Target: 400
• Locations: 3 countries
• Sites: 6

Brief 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).

Conditions

Polyarticular Course Juvenile Idiopathic Arthritis (JIA)

Keywords

JIA; Rheumatology

Outcome Measures

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)

  Month 6

Secondary Outcomes (6)

• PROMIS® Pain Interference at Month 6

  Month 6

• PROMIS® Fatigue at Month 6

  Month 6

• PROMIS® Physical Function at Month 6

  Month 6

• Change in arthritis disease activity (cJADAS10)

  Month 6

• Change in arthritis disease activity (JIA American College of Rheumatology Pediatric 70 [ACR 70]) at Month 6

  Month 6

Study Arms (4)

Second TNFi (Tumor Necrosis Factor inhibitor) medication

ACTIVE COMPARATOR

Adalimumab originator or biosimilar; etanercept originator or biosimilar depending on which TNFi the participant had failed.

Drug: TNFi (Tumor Necrosis Factor inhibitor) medication

Abatacept

ACTIVE COMPARATOR

The 50 mg, 87.5 mg and 125 mg SQ doses will be available for weight-based dosing. All participants randomized to abatacept in the first or second stage randomization will receive abatacept SQ weekly at a dosage based on the participant's body weight

Drug: Abatacept

Tocilizumab originator or biosimilar

ACTIVE COMPARATOR

Tocilizumab will be provided in prefilled syringes (162 mg tocilizumab/0.9 mL solution). All participants randomized to tocilizumab in the first or second stage randomization will be receiving 1 prefilled syringe (162 mg) with a dosing interval based on the body weight criteria.

Drug: Tocilizumab

Tofacitinib

ACTIVE COMPARATOR

Tofacitinib will be provided as oral tablets (tofacitinib citrate 5 mg) and as an oral solution (1 mg/mL). All participants randomized to tofacitinib in the first or second stage randomization will receive tofacitinib oral tablets or oral solution twice daily, approximately 12 hours apart, in the morning and evening, at a dosage based on the participant's body weight .

Drug: Tofacitinib

Interventions

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

Second TNFi (Tumor Necrosis Factor inhibitor) medication

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

Abatacept

Tocilizumab DRUG

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

Tocilizumab originator or biosimilar

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

Tofacitinib

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Duke University: lead
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (6)

University of California San Francisco Pediatric Rheumatology

San Francisco, California, 94158, United States

RECRUITING

University of Florida

Gainesville, Florida, 32610, United States

RECRUITING

Hackensack Meridian Health - Joseph M. Sanzari Children's Hospital

Hackensack, New Jersey, 07601, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Asklepios Children's Hospital

Sankt Augustin, North Rhine-Westphalia, 53757, Germany

RECRUITING

IRCCS Giannina Gaslini Institute

Genoa, Liguria, 16147, Italy

RECRUITING

MeSH Terms

Conditions

Arthritis, Juvenile

Interventions

Tumor Necrosis Factor Inhibitors; Dosage Forms; Abatacept; tocilizumab; tofacitinib

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anti-Inflammatory Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques; Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Central Study Contacts

Laura E Schanberg (Contact PI)

CONTACT

919-373-3863; laura.schanberg@duke.edu

Huiman Barnhart (Dual PI)

CONTACT

919-668-8828; huiman.barnhart@duke.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2024
• First Posted: October 23, 2024
• Study Start: January 9, 2026
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 16, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); DE (1); IT (1)