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Versuch mit sequentiellen Medikamenten nach TNFi-Versagen bei juveniler idiopathischer Arthritis (SMART-JIA)

16. Oktober 2026 aktualisiert von: 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).

Studienübersicht

Status

Rekrutierung

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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.

Studientyp

Interventionell

Einschreibung (Geschätzt)

400

Phase

  • Phase 3

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienkontakt

Studieren Sie die Kontaktsicherung

Studienorte

  • Deutschland
    • North Rhine-Westphalia
      • Sankt Augustin, North Rhine-Westphalia, Deutschland, 53757
        • Rekrutierung
        • Asklepios Children's Hospital
        • Kontakt:
        • Kontakt:
        • Hauptermittler:
          • Gerd Horneff, Prof. Dr.
  • Italien
    • Liguria
      • Genoa, Liguria, Italien, 16147
        • Rekrutierung
        • IRCCS Giannina Gaslini Institute
        • Kontakt:
        • Hauptermittler:
          • Alessandro Consolaro
  • Niederlande
    • Utrecht
      • Utrecht, Utrecht, Niederlande, 3584 CX
        • Rekrutierung
        • University Medical Center Utrecht (Universitair Medisch Centrum Utrecht)
        • Kontakt:
        • Kontakt:
        • Hauptermittler:
          • Joost Swart
  • Vereinigte Staaten
    • California
      • San Francisco, California, Vereinigte Staaten, 94158
        • Rekrutierung
        • University of California San Francisco Pediatric Rheumatology
        • Kontakt:
        • Hauptermittler:
          • Susan Kim
    • Florida
      • Gainesville, Florida, Vereinigte Staaten, 32610
        • Rekrutierung
        • University of Florida
        • Hauptermittler:
          • Melissa Elder
        • Kontakt:
    • New Jersey
      • Hackensack, New Jersey, Vereinigte Staaten, 07601
        • Rekrutierung
        • Hackensack Meridian Health - Joseph M. Sanzari Children's Hospital
        • Hauptermittler:
          • Ginger Janow
        • Kontakt:
    • Ohio
      • Columbus, Ohio, Vereinigte Staaten, 43205

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

2 Jahre bis 21 Jahre (Kind, Erwachsene)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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).

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Sequenzielle Zuweisung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Aktiver Komparator: Second TNFi (Tumor Necrosis Factor inhibitor) medication

Adalimumab originator or biosimilar; etanercept originator or biosimilar depending on which TNFi the participant had failed.
Arzneimittel: 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
Aktiver Komparator: 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
Arzneimittel: 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
Aktiver Komparator: 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.
Arzneimittel: Tocilizumab

<30 kg 162 mg once every 3 weeks

≥30 kg 162 mg once every 2 weeks
Aktiver Komparator: 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 .
Arzneimittel: 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

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Number of participants with MiDA
Zeitfenster: 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

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
PROMIS® Pain Interference at Month 6
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Duke University

Mitarbeiter

Patient-Centered Outcomes Research Institute

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

9. Januar 2026

Primärer Abschluss (Geschätzt)

30. Mai 2029

Studienabschluss (Geschätzt)

1. November 2029

Studienanmeldedaten

Zuerst eingereicht

21. Oktober 2024

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

21. Oktober 2024

Zuerst gepostet (Tatsächlich)

23. Oktober 2024

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

21. Oktober 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

16. Oktober 2026

Zuletzt verifiziert

1. Oktober 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • Pro00115808
  • PLACER-2022C3-30331 (Andere Zuschuss-/Finanzierungsnummer: PCORI)
  • EPM #8533 (Andere Zuschuss-/Finanzierungsnummer: DukeUMC)

Plan für individuelle Teilnehmerdaten (IPD)

Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?

NEIN

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Ja

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

Produkt, das in den USA hergestellt und aus den USA exportiert wird

Ja

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