The Efficacy and Safety of Adalimumab in Non-infectious Anterior Pediatric Uveitis With Peripheral Vascular Leakage

Phase 4

• Conditions: Uveitis, Anterior; Adalimumab
• Interventions: Drug: Methotrexate; Drug: Adalimumab

• Registration Number: NCT05015335
• Lead Sponsor: Peking Union Medical College Hospital

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.

Study Timeline

• Status Verified: 2021-07
• Study First Submitted: 2021-08-10
• Study First Submitted QC: 2021-08-15
• Study Start: 2021-08-19
• Study First Posted: 2021-08-20
• Last Update Submitted: 2021-11-02
• Last Update Posted: 2021-11-10
• Primary Completion: 2022-07
• Study Completion: 2023-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Methotrexate	Methotrexate	Methotrexate given 10mg orally once a week.
Adalimumab	Adalimumab	Adalimumab administered subcutaneously at 40mg every 2 weeks

Primary Outcome Measures

Name	Time	Method
Uveitis flare	At 6 months' follow-up visit	Uveitis flare is defined as anterior chamber cell count grading increased from 0 to 1.; The grading method is in accordance with SUN criteria. Anterior chamber cell count was scored according to Standardization of Uveitis Nomenclature (SUN) criteria

Secondary Outcome Measures

Name	Time	Method
Best corrected visual acuity (BCVA)	At 6 months' follow-up visit	BCVA was transformed into logMar form
Vitreous haze	At 6 months' follow-up visit	Vitreous haze will graded as the same method of anterior chamber cell, the slit lamp will be pushed forward to the vitreous to observe vitreous haze.
frequency of topical steroid eyedrops if any inflammatory flare happens.	At 6 months' follow-up visit	Different GCs eye drops are transformed into equivalent 1% prednisolone for analysis.
Systemic immunomodulatory therapy (sIMT, including GCs and immunosuppressive drugs)load at the 6-month follow-up visit if any inflammatory flare ever happens.	At 6 months' follow-up visit	sIMT load is transformed into a quantizable score based on prior studies in uveitis.
Keratic precipitates	At 6 months' follow-up visit	Keratic precipitates was recorded in a dichotomous method.
Extent of peripheral vascular leakage	At 6 months' follow-up visit	Vascular leakage was quantified based on the method developed by the Angiography Scoring for Uveitis Working Group (ASUWOG), in which vascular leakage in the posterior pole and in each peripheral quadrant was scored 1 if limited and scored 2 if diffuse. Total maximum score will 8 since leakage in the posterior pole will be excluded in this study.
Adverse events	through study completion, an average of 6 months	Adverse events included the infectious events and laboratory parameter abnormalities.

Trial Locations

Locations (1)

Peking University Medical College Hospital; 🇨🇳 Beijing, China