Adalimumab Dose Adjustment for Pediatric Uveitis Treatment Trial

Обзор

The goal of this clinical trial is to learn whether children and young adults with well-controlled juvenile idiopathic arthritis (JIA)-associated uveitis or chronic anterior uveitis can safely take adalimumab (or biosimilar) injections less often while maintaining control of their disease. The main question it aims to answer is: can adalimumab/biosimilar injections be given less frequently without uveitis (eye inflammation) or arthritis (joint inflammation) returning? Researchers will compare adalimumab/biosimilar injection schedules of every 2 weeks, 4 weeks, 8 weeks, and 12 weeks to determine how injection frequency affects disease control. Participants will: * Take adalimumab/biosimilar injections every 2, 4, 8, or 12 weeks. * Attend study visits every 6 weeks over 24 weeks, with an additional follow-up visit at 48 weeks for checkups, tests, and questionnaires. * Keep a diary of how often they take adalimumab/biosimilar and other drugs they take for their uveitis/arthritis.

Вмешательства

• Биопрепарат Adalimumab/Biosimilar
  Adalimumab is a fully human monoclonal anti-tumor necrosis factor alpha antibody - a biologic, immunomodulatory drug. Adalimumab (20mg or 40mg) is a clear, colorless solution available as an injectable auto-pen or pre-filled syringe for subcutaneous injection. All FDA-approved adalimumab biosimilars are allowed for this trial and include: Abrilada (adalimumab-afzb), Amjevita (adalimumab-atto), Cyltezo (adalimumab-adbm), Hadlima (adalimumab-bwwd), Hulio (adalimumab-fkjp), Hyrimoz (adalimumab-adaz

Первичные конечные точки

• Cumulative Incidence of Treatment Failure [Срок оценки: From baseline to 24 weeks post-randomization]

Критерии участия

Критерии включения

• Stated willingness to comply with all study procedures and availability for the duration of the study period
• History of juvenile idiopathic arthritis (JIA) or chronic anterior uveitis (CAU), diagnosed prior to 16 years of age (patient may be older than 16 at time of enrollment)
• ≥2 years of age (per FDA approval for use in children with polyarticular JIA)
• Weight must be ≥15kg
• Formal diagnosis of JIA-associated uveitis or CAU with no other suspected etiology
• ≥24 consecutive months of controlled ocular inflammation (≤0.5+ anterior chamber cell, ≤0.5+ vitreous haze, and no active retinal/choroidal lesions in either eye)
• ≥24 consecutive months of controlled arthritis verified by a pediatric rheumatologist if defined as JIA-associated uveitis
• ≥24 consecutive months of treatment with adalimumab or biosimilar of adalimumab
• ≥180 days on a stable dose of adalimumab or biosimilar of adalimumab; dose must be no greater than 20mg (if weight <30kg), or 40mg (if weight ≥30kg), injected every two weeks
• If on biosimilar of adalimumab, ≥90 days on the biosimilar
• Ability to continue to obtain commercial supply of adalimumab or biosimilar
• If on a conventional disease-modifying anti-rheumatic drug (cDMARD) (injectable or oral methotrexate, mycophenolate mofetil, azathioprine, or leflunomide), dose must be ≤25 mg weekly for methotrexate, ≤3 g daily for mycophenolate mofetil, ≤250 mg daily for azathioprine, or ≤20 mg daily for leflunomide; dose and route of administration must be stable for ≥90 days
• Willingness to limit consumption of alcohol during the study period
• Agreement to avoid live attenuated vaccinations
• Agreement to use highly effective contraception or abstinence for ≥28 days prior to screening and throughout the study period (for males and females of reproductive age)
• Suitable, in the opinion of the Investigator, to continue treatment with adalimumab/biosimilar per regional labeling

Критерии исключения

• History of acute anterior uveitis characterized by redness and symptoms, including but not limited to floaters, pain, and light sensitivity
• Intraocular surgery in the past 90 days or planned surgery in the next 24 weeks
• Severe cataract or opacity preventing view to the posterior pole in both eyes
• Chronic hypotony (<5mmHg for ≥90 days) in either eye
• Treatment with oral corticosteroids or intraocular corticosteroid injection within the last 24 weeks
• Use of topical corticosteroid eye drops within the last 90 days
• Use of nonsteroidal anti-inflammatory drug (NSAID) eye drops within the last 90 days
• Pregnancy or lactation (a pregnancy test will be conducted at baseline and follow-up visits for females post-menarche)
• Presence of intraretinal or subretinal fluid in either eye
• Prior safety or tolerability issues with adalimumab
• History of cancer, active tuberculosis, or hepatitis B
• Other medical condition expected to dictate treatment course during the study
• Any of the following laboratory test results on their most recent tests within the past 90 days prior to screening/enrollment: leukocyte count <2500, platelet count ≤75000, hemoglobin<9.0, aspartate transaminase (AST) or alanine transaminase (ALT) ≥ 2 times the upper limit of normal range, creatinine ≥1.5

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 9 центров

• University of California, Los Angeles — Los Angeles
• University of California, Davis — Sacramento
• University of California, San Francisco — San Francisco
• University of Miami — Miami
• Children's Mercy Hospital — Kansas City
• Cincinnati Children's Hospital — Cincinnati
• Vanderbilt University Medical Center — Nashville
• University of Texas, Austin — Austin
• … и ещё 1 центр

Великобритания · 8 центров

• University Hospitals Bristol and Weston — Bristol
• University Hospitals of Leicester — Leicester
• Alder Hey Children's Hospital — Liverpool
• Great Ormond Street Hospital — London
• Manchester University NHS Foundation Trust — Manchester
• Great North Children's Hospital — Newcastle upon Tyne
• Norfolk and Norwich University Hospital — Norwich
• Sheffield Children's Hospital — Sheffield

Италия · 1 центр

• Meyer Children's Hospital — Florence

Публикации

• Quartier P, Baptiste A, Despert V, Allain-Launay E, Kone-Paut I, Belot A, Kodjikian L, Monnet D, Weber M, Elie C, Bodaghi B; ADJUVITE Study Group. ADJUVITE: a double-blind, randomised, placebo-controlled trial of adalimumab in early onset, chronic, juvenile idiopathic arthritis-associated anterior uveitis. Ann Rheum Dis. 2018 Jul;77(7):1003-1011. doi: 10.1136/annrheumdis-2017-212089. Epub 2017 Dec PMID 29275333
• Pichi F, Smith SD, Goldstein DA, Baddar D, Gerges TKA, Janetos TM, Ruiz-Cruz M, Elena Concha-Del-Rio L, Maruyama K, Carina Ten Berge J, Rombach SM, Cimino L, Bolletta E, Miserocchi E, Scandale P, Serafino M, Camicione P, Androudi S, Gonzalez-Lopez JJ, Lim LL, Singh N, Gupta V, Gupta N, Amer R, Dodds EM, Inchauspe S, Munk MR, Donicova E, Carreno E, Takeuchi M, Chee SP, Chew MC, Agarwal A, Schlaen A PMID 37734639
• Ramanan AV, Dick AD, Jones AP, McKay A, Williamson PR, Compeyrot-Lacassagne S, Hardwick B, Hickey H, Hughes D, Woo P, Benton D, Edelsten C, Beresford MW; SYCAMORE Study Group. Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis. N Engl J Med. 2017 Apr 27;376(17):1637-1646. doi: 10.1056/NEJMoa1614160. PMID 28445659
• Acharya NR, Ramanan AV, Coyne AB, Dudum KL, Rubio EM, Woods SM, Guly CM, Moraitis E, Petrushkin HJD, Armon K, Puvanachandra N, Choi JT, Hawley DP, Arnold BF; ADJUST Study Group. Stopping of adalimumab in juvenile idiopathic arthritis-associated uveitis (ADJUST): a multicentre, double-masked, randomised controlled trial. Lancet. 2025 Jan 25;405(10475):303-313. doi: 10.1016/S0140-6736(24)02468-1. PMID 39863370

Идентификаторы

NCT: NCT07699107 · 25-45347 · UG1EY038172

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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