Trial of Sequential Medications AfteR TNFi Failure in Juvenile Idiopathic Arthritis (SMART-JIA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Duke Clinical Research Institute

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2026-02-11

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Patient-Centered Outcomes Research Institute (PCORI)

External identifiers

EU CT number

2025-520923-25-00

WHO UTN

U1111-1322-4869

ClinicalTrials.gov

NCT06654882

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the comparative effectiveness of treatment with each of 3 non-TNFi medications individually vs. treatment with a second TNFi to achieve minimal disease activity (MiDA; cJADAS10 less or equal to 5) at 6 months in children with Polyarticular course juvenile idiopathic arthritis (pcJIA) refractory to pre-trial TNFi treatment. The primary hypothesis is to establish superiority by showing that a higher proportion of children in each of the 3 non-TNFi treatment groups achieve MiDA at 6 months compared to children treated with a second TNFi.

Secondary objectives 3

1. To compare patient and caregiver reported outcomes (PROs [PROMIS® pain interference, fatigue, and mobility measures]) and change in arthritis disease activity (cJADAS10 and JIA American College of Rheumatology Pediatric 70 [ACR 70]) after treatment with each of 3 non-TNFi medications vs. treatment with a second TNFi at 6 months.
2. To evaluate the treatment strategies embedded in the SMART design at 12 months, where a treatment strategy comprises a sequence of a non-TNFi or second TNFi medication followed by a subsequent medication for poor responders.
3. To optimize study recruitment and retention by identifying barriers and developing improved patient-facing materials and processes using Design Thinking methods.

Conditions and MedDRA coding

Juvenile Idiopathic Arthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Polyarticular course JIA
2. Moderate or high-disease activity (cJADAS10 >5) despite treatment with an initial TNFi for greater than or equal to 3 months
3. Age higher or equal to 2 years and <18 years and weight greater than or equal to 10 kg
4. No systemic glucocorticoids or systemic glucocorticoids at a stable dose of less or equal to 0.2 mg/kg/day (maximum 10 mg/day) for more or equal to 2 weeks prior to baseline visit
5. Documented informed consent/assent obtained from the parent/caregiver/patient
6. Females of childbearing potential are eligible only if they agree to use the required contraception methods or are not sexually active

Exclusion criteria 22

1. Systemic JIA
2. Prior treatment with non-TNFi bDMARDs and/or any JAKi
3. Aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than or equal to 1.5 x upper limit of normal (ULN) for age and sex
4. Serum creatinine > 1.5 x ULN for age and sex
5. Platelet count <150 x 10^3/microlitre (<150,000/mm^3)
6. Hemoglobin less than or equal to 9.0 g/dL (less than or equal to 5.6 mmol/L)
7. White blood cell (WBC) count <3,000/mm^3 (<3.0 x 10^9/L)
8. Neutrophil count less than or equal to 2000/mm^3 (less than or equal to 2.0 x 10^9/L)
9. Absolute lymphocyte count less than or equal to 500 cells/m^3
10. Any active acute, subacute, chronic, or recurrent bacterial, viral (including HIV, HCV, and HBV), 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. HBsAg positive and HBcAb negative: Participant is excluded from study. HBsAg negative and HBcAb positive and HBsAb negative: Participant is excluded from study. HCV Ab positive and HCV RNA positive: Participant is excluded from study (HCV RNA sample collection may be deferred and collected only if required to confirm eligibility in HCV Ab positive patients). HIV-1 or HIV-2 antibody positive: Participant is excluded from study.
11. Any medical history considered a contraindication/safety concern by the study investigator with the use of adalimumab, etanercept, tofacitinib, ABA, or an IL-6 inhibitor or their biosimilars. In particular, subjects at high risk for venous thromboembolism will be excluded. A subject may be at high risk for venous thromboembolism if they: - have heart failure or prior myocardial infarction within past 3 months; -have inherited coagulation disorders;-have had venous thromboembolism, either deep venous thrombosis or pulmonary embolism; -are undergoing major surgery or is immobilized.
12. Enthesitis-related arthritis/juvenile spondyloarthritis (2001 International League of Associations for Rheumatology [ILAR] criteria)
13. Pregnant or breastfeeding
14. History of or currently active inflammatory bowel disease
15. History of or currently active psoriasis
16. Active uveitis within 3 months of the baseline visit
17. History of or currently active sacroiliitis
18. History of or current malignancy
19. 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.
20. Prior treatment with more than one TNFi molecule; exposure to more than one biosimilar of the same TNFi molecule is allowed
21. Any live attenuated vaccine, such as varicella-zoster, oral polio, measles, mumps or rubella vaccines, within 4 weeks prior to the baseline visit and throughout the study. Killed or inactive vaccine may be permitted based on the investigator’s judgment.
22. History of hypersensitivity or allergic reaction to any study drug or any of its excipients (inactive ingredients).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Minimal disease activity (MiDA) at Month 6 as assessed by the cJADAS10 less than or equal to 5

Secondary endpoints 5

1. PROMIS® pain interference at Month 6
2. PROMIS® fatigue at Month 6
3. PROMIS® mobility at Month 6
4. Change in arthritis disease activity (cJADAS10 and JIA American College of Rheumatology Pediatric 70 [ACR 70]) at Month 6
5. Change in arthritis disease activity (cJADAS10) at Month 12

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Duke Clinical Research Institute

Sponsor organisation

Duke Clinical Research Institute

Address

2400 Pratt Street

City

Durham

Postcode

27705-3976

Country

United States

Scientific contact point

Organisation

Duke Clinical Research Institute

Contact name

IRCCS Istituto Giannina Gaslini, delegated by the Sponsor

Public contact point

Organisation

Duke Clinical Research Institute

Contact name

IRCCS Istituto Giannina Gaslini, delegated by the Sponsor

Locations

3 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 72 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications