Clinical trial NCT05015335: The Efficacy and Safety of Adalimumab in Non-infectious Anterior Pediatric Uveitis With Peripheral Vascular Leakage
Official title: The Efficacy and Safety of Adalimumab for Inflammatory Flare Prevention in Non-infectious Anterior Pediatric Uveitis With Peripheral Vascular Leakage Compared With Methotrexate, a RCT Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Uveitis, Anterior
Adalimumab
Keywords: pheripheral retinal vasuclar leakage
adalimumab
methotrexate
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2021-08-20
Enrollment: 50
Sex: ALL
Minimum age (years): 4
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a prospective, single-center,open-lablel, interventional, randomizedcontrolled clinical trial that will be performed at the Ophthalmology Department, Peking Union Medical College Hospital.
Primary purpose: PREVENTION

Brief summary: Children with anterior uveitis are prone to suffer from chronic recurrent course of intraocular inflammation and adverse effects of glucocorticosteroids (GCs) /immunomodulatory treatment (IMT) agents. The performance of adalimumab has been shown to be fairly favorable in treating refractory non-infectious uveitis. This study aims to assess the efficacy and safety of adalimumab for inflammatory flare prevention in non-infectious anterior pediatric uveitis with peripheral vascular leakage compared with methotrexate. Children weighed ≥ 30kg and aged between 4-16 years old with active chronic non-infectious anterior uveitis with peripheral retinal vascular leakage on ultra wildfield fluorescence fundus angiography (UWFFA) will be included. They will be treated with a predesigned inflammatory control regimen to reach inflammatory quiescence in 1 month. After that they will be treated with either MTX or adalimumab and regularly followed up for at least 6 months. The primary endpoint is treatment failure defined as any inflammatory fare with anterior chamber cell count grading increased from 0 to 1. Secondary endpoints are best corrected visual acuity (BCVA), inflammation parameters (keratic precipitates, vitreous haze grades), extent of vascular leakage, frequency of topical steroid eyedrops, systemic immunosuppressive drug load, and adverse events.

Detailed description: This is a prospective, single-center, interventional, randomized, non-blinded, controlled clinical trial that will be performed at the Ophthalmology Department, Peking Union Medical College Hospital.

Children with active noninfectious anterior uveitis demonstrating peripheral vascular leakage on UWFFA and meet the selection criteria will be randomly assigned to treatment group or control group.

Both groups will be treated with a predesigned plan for the active inflammation. At one month or when patients' ocular inflammation gets controlled to 0.5+ cell in the anterior chamber, whichever comes later, patients in the treatment group will be given adalimumab subcutaneously at 40mg every 2 weeks, patients in the control group will be given methotrexate10mg orally once a week.

Follow-up visits will be scheduled every two weeks at the run-in period and the first month after randomization, and every month from the second to the sixth month.

The primary endpoint is treatment failure defined as any inflammatory fare with anterior chamber cell count grading increased from 0 to 1.

Secondary endpoints are best corrected visual acuity (BCVA), inflammation parameters (keratic precipitates, vitreous haze grades), extent of vascular leakage, frequency of topical steroid eyedrops, systemic immunosuppressive drug load, and adverse events.

Eligibility criteria: Inclusion Criteria:

1. Children with noninfectious uveitis aged between 4-16, weight ≥ 30kg.
2. Uveitis resistant to well conducted topical steroid therapy for three months, or uveitis resistant to well conducted 0.1% prednisolone twice a day for one month
3. Retina peripheral vascular leakage demonstrated by UWFFA at the time of inclusion.

Exclusion Criteria:

1. Any contraindication to administration of immunosuppressive therapy (active tuberculosis, immune deficit, opportunistic infection, other severe chronic disease).
2. Previous diagnosis or signs of demyelinating disease of the central nervous system.
3. Children unable to cooperate with examinations and follow-up.
4. Positive allergy skin test when conducting fluorescence fundus angiography.
5. Diffuse vascular leakage, macula edema or any retina lesions demonstrated by UWFFA.
6. History of oral immunosuppressive drug treatment within 2 months
7. History of biological treatment within 2 months
8. History of triamcinolone acetonide subconjunctival/intraocular injection within 3 months
9. Current topical steroid use more than six times per day
10. History of eye surgery within 3 months.
11. Eye complications that interfere with fundus observation.

Primary outcomes:
measure: Uveitis flare
timeFrame: At 6 months' follow-up visit
Secondary outcomes:
measure: Extent of peripheral vascular leakage
timeFrame: At 6 months' follow-up visit
measure: Keratic precipitates
timeFrame: At 6 months' follow-up visit
measure: Vitreous haze
timeFrame: At 6 months' follow-up visit
measure: Best corrected visual acuity (BCVA)
timeFrame: At 6 months' follow-up visit
measure: Adverse events
timeFrame: through study completion, an average of 6 months
measure: frequency of topical steroid eyedrops if any inflammatory flare happens.
timeFrame: At 6 months' follow-up visit
measure: Systemic immunomodulatory therapy (sIMT, including GCs and immunosuppressive drugs)load at the 6-month follow-up visit if any inflammatory flare ever happens.
timeFrame: At 6 months' follow-up visit
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Medical College Hospital
Study officials:
affiliation: Peking Union Medical College Hospital
name: Meifen Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References:
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