Polyarticular Course Juvenile Idiopathic Arthritis (JIA)Phase 3SMART-JIANCT06654882
Trial of Sequential Medications AfteR TNFi Failure in Juvenile Idiopathic Arthritis
A Phase 3 study testing TNFi (Tumor Necrosis Factor inhibitor) medication, Abatacept and Tocilizumab in people with Polyarticular Course Juvenile Idiopathic Arthritis (JIA), run by Duke University at 7 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 to 21 years
- Conditions the study is for
- Polyarticular Course Juvenile Idiopathic Arthritis (JIA)
- What is being tested?
- TNFi (Tumor Necrosis Factor inhibitor) medication, Abatacept and Tocilizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 7 sitesin 4 countries
- Study dates
- 9 Jan 2026to Nov 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
- Documented informed consent/assent obtained from the parent/caregiver/patient
Who cannot join
- 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
Show all 22Show fewer
- 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 live attenuated vaccine, such as varicella-zoster, oral polio, measles, mumps or rubella vaccines, within 4 weeks prior to the baseline 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 particular, subjects at known high risk for venous thromboembolism will be excluded, including recent heart failure or prior myocardial infarction, known inherited thrombotic risk factors, history of venous thromboembolism (deep venous thrombosis or pulmonary embolism, undergoing major surgery, or are chronically immobilized).
- Pregnant or breastfeeding
- Sexually active females of childbearing potential who refuse to use at least one required contraception method (See Contraception paragraph 8.9 for definition of childbearing potential and details).
- History of hypersensitivity or allergic reaction to any study drug or any of its excipients (inactive ingredients).
Trial locations and contacts
7 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
7 sites in 4 countries
United States4 sites, 4 recruiting
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205
Study Coordinator, 614-722-5525, joanne.drew@nationwidechildrens.org
Alysha Taxter
- Recruiting
University of Florida
Gainesville, Florida, 32610
Study Coordinator, 352-294-8556, melissa.lingis@peds.ufl.edu
Melissa Elder
- Recruiting
Hackensack Meridian Health - Joseph M. Sanzari Children's Hospital
Hackensack, New Jersey, 07601
Clinical Research Coordinator, 551-996-3345, kate.sidwell@hmhn.org
Ginger Janow
- Recruiting
University of California San Francisco Pediatric Rheumatology
San Francisco, California, 94158
Study Coordinator, 415-353-1301, zilan.zheng@ucsf.edu
Susan Kim
Germany1 site, 1 recruiting
- Recruiting
Asklepios Children's Hospital
Sankt Augustin, North Rhine-Westphalia, 53757
Jana Kipp, +49 (2241) 249-201, j.kipp@asklepios.com
Verena Lutz-Wiegers, v.lutz@asklepios.com
Italy1 site, 1 recruiting
- Recruiting
IRCCS Giannina Gaslini Institute
Genoa, Liguria, 16147
Research Assistant, +39 010 56361, elisapatrone@gaslini.org
Alessandro Consolaro
Netherlands1 site, 1 recruiting
- Recruiting
University Medical Center Utrecht (Universitair Medisch Centrum Utrecht)
Utrecht, Utrecht, 3584 CX
Sabine Michel Site Study Coordinator, +31 88 755 5555, S.Michel-2@umcutrecht.nl
Jojanneke J. Scheepstra Site Study Coordinator, +31 88 755 5555, J.Scheepstra@umcutrecht.nl
About this study
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).
Read the detailed description
The goal of the study is to provide an evidence base for selecting sequential medication(s) if a JIA patient fails initial bDMARD. SMART-JIA is a pragmatic, international, open-label, randomized trial comparing treatment with a second TNFi (active control) to each of 3 different medications (IL-6i, JAKi, or ABA) in children aged 2 to 21 years with pcJIA and inadequate response to initial TNFi. Leveraging sequential multiple assignment randomized trial (SMART) design methodology, we will implement a second randomization to assess the effectiveness of changing medication if there is inadequate response to the first study medication. This approach allows identification of optimal strategies for medication sequencing based on individual characteristics and provides critical insights to inform future studies.
SMART-JIA will study the efficacy of a second TNFi (active control) compared to each of 3 other already US Food and Drug Administration (FDA)-approved and European Union (EU)-approved non-TNFi medications currently used to treat pcJIA (IL-6i, JAKi, and ABA). TNFi, IL-6i, and ABA are administered by subcutaneous (SQ) injection weekly, or every other week, or every three weeks, and JAKi (e.g., tofacitinib) is taken orally twice daily. All study treatments have similar safety profiles and are standard of care (SOC) worldwide. This in addition to the pragmatic and full-scale nature of the trial will ensure its completion. Successful completion of this trial will substantially impact the clinical care and outcomes of children with pcJIA, shifting the current trial-and-error treatment paradigm to a smart, precise approach.
- Being tested
- TNFi (Tumor Necrosis Factor inhibitor) medication, Abatacept, Tocilizumab, Tofacitinib
- Keywords
- JIA, Rheumatology
- Medical subject headings
- Arthritis, Juvenile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TNFi (Tumor Necrosis Factor inhibitor) medicationDrug
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
AbataceptDrug
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
TocilizumabDrug
<30 kg 162 mg once every 3 weeks
≥30 kg 162 mg once every 2 weeks
TofacitinibDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: 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. Receives: 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 . Receives: Drug: Tofacitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Month 6
Secondary outcomes (6)
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.
Measured: Month 6
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.
Measured: Month 6
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.
Measured: Month 6
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.
Measured: Month 6
Change in arthritis disease activity (JIA American College of Rheumatology Pediatric 70 [ACR 70]) at Month 6
The ACR score is a scale to measure change in rheumatoid arthritis symptoms.
An ACR70 response represents at least a 70% improvement in tender and swollen joint counts.
Measured: Month 6
Number of participants with MiDA (Change in arthritis disease activity [cJADAS10] at Month 12)
Minimal disease activity (MiDA) at Month 12 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.
Measured: Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2024
- Study start9 Jan 2026
- Primary completion30 May 2029 (estimated)
- Study completionNov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Polyarticular Course Juvenile Idiopathic Arthritis (JIA)Studies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06654882
- Sponsor's protocol ID
- Pro00115808
- Other IDs
- PLACER-2022C3-30331, EPM #8533
- Acronym
- SMART-JIA
- Status last verified
- Oct 2026
- First submitted
- 21 Oct 2024
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No