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幼年特发性关节炎 TNFi 失败后序贯用药的试验 (SMART-JIA)

2026年10月16日 更新者：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).

研究概览

地位

招聘中

条件

干预/治疗

详细说明

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.

研究类型

介入性

注册 (估计的)

400

阶段

  • 第三阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

  • 德国
    • North Rhine-Westphalia
      • Sankt Augustin、North Rhine-Westphalia、德国、53757
        • 招聘中
        • Asklepios Children's Hospital
        • 接触：
        • 接触：
        • 首席研究员：
          • Gerd Horneff, Prof. Dr.
  • 意大利
    • Liguria
      • Genoa、Liguria、意大利、16147
        • 招聘中
        • IRCCS Giannina Gaslini Institute
        • 接触：
        • 首席研究员：
          • Alessandro Consolaro
  • 美国
    • California
      • San Francisco、California、美国、94158
        • 招聘中
        • University of California San Francisco Pediatric Rheumatology
        • 接触：
        • 首席研究员：
          • Susan Kim
    • Florida
      • Gainesville、Florida、美国、32610
        • 招聘中
        • University of Florida
        • 首席研究员：
          • Melissa Elder
        • 接触：
    • New Jersey
      • Hackensack、New Jersey、美国、07601
        • 招聘中
        • Hackensack Meridian Health - Joseph M. Sanzari Children's Hospital
        • 首席研究员：
          • Ginger Janow
        • 接触：
    • Ohio
      • Columbus、Ohio、美国、43205
        • 招聘中
        • Nationwide Children's Hospital
        • 接触：
        • 首席研究员：
          • Alysha Taxter
  • 荷兰
    • Utrecht
      • Utrecht、Utrecht、荷兰、3584 CX
        • 招聘中
        • University Medical Center Utrecht (Universitair Medisch Centrum Utrecht)
        • 接触：
        • 接触：
        • 首席研究员：
          • Joost Swart

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

2年 至 21年 (孩子、成人)

接受健康志愿者

不

有资格学习的性别

全部

描述

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).

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：顺序分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
有源比较器：Second TNFi (Tumor Necrosis Factor inhibitor) medication

Adalimumab originator or biosimilar; etanercept originator or biosimilar depending on which TNFi the participant had failed.
药品：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
有源比较器：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
药品：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
有源比较器：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.
药品：Tocilizumab

<30 kg 162 mg once every 3 weeks

≥30 kg 162 mg once every 2 weeks
有源比较器：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 .
药品：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

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Number of participants with MiDA
大体时间：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

次要结果测量

结果测量
措施说明
大体时间
PROMIS® Pain Interference at Month 6
大体时间：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
大体时间：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
大体时间：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)
大体时间：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
大体时间：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)
大体时间：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

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Duke University

合作者

Patient-Centered Outcomes Research Institute

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2026年1月9日

初级完成 (估计的)

2029年5月30日

研究完成 (估计的)

2029年11月1日

研究注册日期

首次提交

2024年10月21日

首先提交符合 QC 标准的

2024年10月21日

首次发布 (实际的)

2024年10月23日

研究记录更新

最后更新发布 (实际的)

2026年10月21日

上次提交的符合 QC 标准的更新

2026年10月16日

最后验证

2026年10月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • Pro00115808
  • PLACER-2022C3-30331 (其他赠款/资助编号：PCORI)
  • EPM #8533 (其他赠款/资助编号：DukeUMC)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

在美国制造并从美国出口的产品

是的

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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