Juvenile Idiopathic Arthritis Associated Uveitis, Uveitis, Anterior
Conditions
Keywords
Adalimumab, JIA-associated uveitis, Chronic anterior uveitis, reduced frequency dosing
Brief summary
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.
Interventions
BIOLOGICALAdalimumab/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), Idacio (adalimumab-aacf), Simlandi (adalimumab-ryvk), Yuflyma (adalimumab-aaty), and Yusimry (adalimumab-aqvh).
Sponsors
Nisha Acharya
National Eye Institute (NEI)
National Institutes of Health (NIH)
University of California, San Francisco
University of California, Davis
University of California, Los Angeles
Children's Hospital Medical Center, Cincinnati
Children's Mercy Hospital Kansas City
University of Miami
University of Utah
University of Texas at Austin
Vanderbilt University Medical Center
University Hospitals Bristol and Weston NHS Foundation Trust
Alder Hey Children's NHS Foundation Trust
Great Ormond Street Hospital for Children NHS Foundation Trust
Norfolk and Norwich University Hospitals NHS Foundation Trust
Manchester University NHS Foundation Trust
Sheffield Children's NHS Foundation Trust
University Hospitals, Leicester
Meyer Children's Hospital IRCCS
Newcastle-upon-Tyne Hospitals NHS Trust
Moorfields Eye Hospital NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Treatment Failure | From baseline to 24 weeks post-randomization | Proportion of participants in each treatment arm experiencing treatment failure by Week 24. Treatment failure is defined by recurrence of ocular inflammation (at least one of the following in at least one eye): * \>0.5+ anterior chamber (AC) cell at a single visit as defined by the Standardization of Uveitis Nomenclature (SUN) criteria * \>0.5+ vitreous haze at a single visit * Active retinal/choroidal inflammation and/or macular edema in either eye at a single visit. Macular edema is defined as central subfield thickness on optical coherence tomography (OCT) \>2 standard deviations above normal thickness (\>320µm on Spectralis or \>300µm on Zeiss or Topcon) and having a greater than 20% increase from baseline and/or presence of intraretinal or subretinal fluid. Treatment failure may also be defined as recurrence of joint disease persistent and severe enough to necessitate unmasking to manage the arthritis recurrence. |
Countries
Italy, United Kingdom, United States
Contacts
CONTACTNisha Acharya, MD MS
PRINCIPAL_INVESTIGATORNisha Acharya, MD MS
University of California, San Francisco
Outcome results
None listed