Исследование последовательного применения лекарств после неэффективности TNFi при ювенильном идиопатическом артрите (SMART-JIA)
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).
Обзор исследования
Статус
Подробное описание
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.
Тип исследования
Регистрация (Оцененный)
Фаза
- Фаза 3
Контакты и местонахождение
Контакты исследования
- Имя: Laura E Schanberg (Contact PI)
- Номер телефона: 919-373-3863
- Электронная почта: laura.schanberg@duke.edu
Учебное резервное копирование контактов
- Имя: Huiman Barnhart (Dual PI)
- Номер телефона: 919-668-8828
- Электронная почта: huiman.barnhart@duke.edu
Места учебы
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North Rhine-Westphalia
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Sankt Augustin, North Rhine-Westphalia, Германия, 53757
- Рекрутинг
- Asklepios Children's Hospital
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Контакт:
- Jana Kipp
- Номер телефона: +49 (2241) 249-201
- Электронная почта: j.kipp@asklepios.com
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Контакт:
- Verena Lutz-Wiegers
- Электронная почта: v.lutz@asklepios.com
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Главный следователь:
- Gerd Horneff, Prof. Dr.
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Liguria
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Genoa, Liguria, Италия, 16147
- Рекрутинг
- IRCCS Giannina Gaslini Institute
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Контакт:
- Research Assistant
- Номер телефона: +39 010 56361
- Электронная почта: elisapatrone@gaslini.org
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Главный следователь:
- Alessandro Consolaro
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Utrecht
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Utrecht, Utrecht, Нидерланды, 3584 CX
- Рекрутинг
- University Medical Center Utrecht (Universitair Medisch Centrum Utrecht)
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Контакт:
- Sabine Michel Site Study Coordinator
- Номер телефона: +31 88 755 5555
- Электронная почта: S.Michel-2@umcutrecht.nl
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Контакт:
- Jojanneke J. Scheepstra Site Study Coordinator
- Номер телефона: +31 88 755 5555
- Электронная почта: J.Scheepstra@umcutrecht.nl
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Главный следователь:
- Joost Swart
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California
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San Francisco, California, Соединенные Штаты, 94158
- Рекрутинг
- University of California San Francisco Pediatric Rheumatology
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Контакт:
- Study Coordinator
- Номер телефона: 415-353-1301
- Электронная почта: zilan.zheng@ucsf.edu
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Главный следователь:
- Susan Kim
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Florida
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Gainesville, Florida, Соединенные Штаты, 32610
- Рекрутинг
- University of Florida
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Главный следователь:
- Melissa Elder
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Контакт:
- Study Coordinator
- Номер телефона: 352-294-8556
- Электронная почта: melissa.lingis@peds.ufl.edu
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New Jersey
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Hackensack, New Jersey, Соединенные Штаты, 07601
- Рекрутинг
- Hackensack Meridian Health - Joseph M. Sanzari Children's Hospital
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Главный следователь:
- Ginger Janow
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Контакт:
- Clinical Research Coordinator
- Номер телефона: 551-996-3345
- Электронная почта: kate.sidwell@hmhn.org
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Ohio
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Columbus, Ohio, Соединенные Штаты, 43205
- Рекрутинг
- Nationwide Children's Hospital
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Контакт:
- Study Coordinator
- Номер телефона: 614-722-5525
- Электронная почта: joanne.drew@nationwidechildrens.org
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Главный следователь:
- Alysha Taxter
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
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).
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Рандомизированный
- Интервенционная модель: Последовательное назначение
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
|
Активный компаратор: Second TNFi (Tumor Necrosis Factor inhibitor) medication
Adalimumab originator or biosimilar; etanercept originator or biosimilar depending on which TNFi the participant had failed. |
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 |
|
Активный компаратор: 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 |
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 |
|
Активный компаратор: 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. |
<30 kg 162 mg once every 3 weeks ≥30 kg 162 mg once every 2 weeks |
|
Активный компаратор: 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 . |
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 |
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Number of participants with MiDA
Временное ограничение: 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:
|
Month 6
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
PROMIS® Pain Interference at Month 6
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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)
Временное ограничение: 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
Временное ограничение: 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)
Временное ограничение: 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
|
Соавторы и исследователи
Спонсор
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
- Заболевания опорно-двигательного аппарата
- Артрит
- Заболевания суставов
- Ревматические заболевания
- Заболевания соединительной ткани
- Аутоиммунные заболевания
- Заболевания иммунной системы
- Заболевания кожи и соединительной ткани
- Артрит, ювенильный
- Противовоспалительные агенты
- Иммуноконъюгаты
- Аминокислоты, пептиды и белки
- Белки
- Фармацевтические препараты
- Следственные методы
- Фармакологические действия
- Химические действия и используют
- Терапевтическое использование
- Антитела
- Иммуноглобулины
- Белки крови
- Сывороточные глобулины
- Глобулины
- Технология, фармацевтическая
- Абатацепт
- Ингибиторы фактора некроза опухоли
- Дозировка форм
- Tocelizumab
- тофацитиниб
Другие идентификационные номера исследования
- Pro00115808
- PLACER-2022C3-30331 (Другой номер гранта/финансирования: PCORI)
- EPM #8533 (Другой номер гранта/финансирования: DukeUMC)
Планирование данных отдельных участников (IPD)
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Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
продукт, произведенный в США и экспортированный из США.
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .