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Prova di farmaci sequenziali dopo il fallimento del TNFi nell'artrite idiopatica giovanile (SMART-JIA)

16 ottobre 2026 aggiornato da: Duke University

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).

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Stimato)

400

Fase

  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

Luoghi di studio

  • Germania
    • North Rhine-Westphalia
      • Sankt Augustin, North Rhine-Westphalia, Germania, 53757
        • Reclutamento
        • Asklepios Children's Hospital
        • Contatto:
        • Contatto:
        • Investigatore principale:
          • Gerd Horneff, Prof. Dr.
  • Italia
    • Liguria
      • Genoa, Liguria, Italia, 16147
        • Reclutamento
        • IRCCS Giannina Gaslini Institute
        • Contatto:
        • Investigatore principale:
          • Alessandro Consolaro
  • Olanda
    • Utrecht
      • Utrecht, Utrecht, Olanda, 3584 CX
        • Reclutamento
        • University Medical Center Utrecht (Universitair Medisch Centrum Utrecht)
        • Contatto:
        • Contatto:
        • Investigatore principale:
          • Joost Swart
  • Stati Uniti
    • California
      • San Francisco, California, Stati Uniti, 94158
        • Reclutamento
        • University of California San Francisco Pediatric Rheumatology
        • Contatto:
        • Investigatore principale:
          • Susan Kim
    • Florida
      • Gainesville, Florida, Stati Uniti, 32610
        • Reclutamento
        • University of Florida
        • Investigatore principale:
          • Melissa Elder
        • Contatto:
    • New Jersey
      • Hackensack, New Jersey, Stati Uniti, 07601
        • Reclutamento
        • Hackensack Meridian Health - Joseph M. Sanzari Children's Hospital
        • Investigatore principale:
          • Ginger Janow
        • Contatto:
    • Ohio
      • Columbus, Ohio, Stati Uniti, 43205
        • Reclutamento
        • Nationwide Children's Hospital
        • Contatto:
        • Investigatore principale:
          • Alysha Taxter

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 2 anni a 21 anni (Bambino, Adulto)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • 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

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 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).

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione sequenziale
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: Second TNFi (Tumor Necrosis Factor inhibitor) medication

Adalimumab originator or biosimilar; etanercept originator or biosimilar depending on which TNFi the participant had failed.
Droga: TNFi (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
Comparatore attivo: Abatacept

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
Droga: Abatacept

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
Comparatore attivo: Tocilizumab originator or biosimilar

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.
Droga: Tocilizumab

<30 kg 162 mg once every 3 weeks

≥30 kg 162 mg once every 2 weeks
Comparatore attivo: Tofacitinib

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 .
Droga: Tofacitinib

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

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Number of participants with MiDA
Lasso di tempo: Month 6

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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
PROMIS® Pain Interference at Month 6
Lasso di tempo: 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.
Month 6
PROMIS® Fatigue at Month 6
Lasso di tempo: 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.
Month 6
PROMIS® Physical Function at Month 6
Lasso di tempo: 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.
Month 6
Change in arthritis disease activity (cJADAS10)
Lasso di tempo: Month 6

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.
Month 6
Change in arthritis disease activity (JIA American College of Rheumatology Pediatric 70 [ACR 70]) at Month 6
Lasso di tempo: 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.
Month 6
Number of participants with MiDA (Change in arthritis disease activity [cJADAS10] at Month 12)
Lasso di tempo: 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.
Month 12

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Duke University

Collaboratori

Patient-Centered Outcomes Research Institute

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

9 gennaio 2026

Completamento primario (Stimato)

30 maggio 2029

Completamento dello studio (Stimato)

1 novembre 2029

Date di iscrizione allo studio

Primo inviato

21 ottobre 2024

Primo inviato che soddisfa i criteri di controllo qualità

21 ottobre 2024

Primo Inserito (Effettivo)

23 ottobre 2024

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

21 ottobre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

16 ottobre 2026

Ultimo verificato

1 ottobre 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • Pro00115808
  • PLACER-2022C3-30331 (Altro numero di sovvenzione/finanziamento: PCORI)
  • EPM #8533 (Altro numero di sovvenzione/finanziamento: DukeUMC)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

prodotto fabbricato ed esportato dagli Stati Uniti

Sì

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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