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

NCT ID: NCT05015335

Last Updated: 2021-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-19

Study Completion Date

2023-07-31

Brief Summary

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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

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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.

Conditions

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Uveitis, Anterior Adalimumab

Keywords

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pheripheral retinal vasuclar leakage adalimumab methotrexate

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Adalimumab

Adalimumab administered subcutaneously at 40mg every 2 weeks

Group Type EXPERIMENTAL

Adalimumab

Intervention Type DRUG

ADA 40mg q2w

Methotrexate

Methotrexate given 10mg orally once a week.

Group Type ACTIVE_COMPARATOR

Methotrexate

Intervention Type DRUG

MTX 10mg qw

Interventions

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Adalimumab

ADA 40mg q2w

Intervention Type DRUG

Methotrexate

MTX 10mg qw

Intervention Type DRUG

Other Intervention Names

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ADA MTX

Eligibility Criteria

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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.
Minimum Eligible Age

4 Years

Maximum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Peking Union Medical College Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Meifen Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Peking Union Medical College Hospital

Locations

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Peking University Medical College Hospital

Beijing, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Hang Song, MD

Role: CONTACT

Phone: +86 15600612346

Email: [email protected]

Meifen Zhang, MD

Role: CONTACT

Phone: +86 13681566748

Email: [email protected]

Facility Contacts

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Hang Hang, MD

Role: primary

References

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Agrawal R, Agarwal A, Jabs DA, Kee A, Testi I, Mahajan S, McCluskey PJ, Gupta A, Palestine A, Denniston A, Banker A, Invernizzi A, Fonollosa A, Sharma A, Kumar A, Curi A, Okada A, Schlaen A, Heiligenhaus A, Kumar A, Gurbaxani A, Bodaghi B, Islam Shah B, Lowder C, Tappeiner C, Muccioli C, Vasconcelos-Santos DV, Goldstein D, Behra D, Das D, Makhoul D, Baglivo E, Denisova E, Miserocchi E, Carreno E, Asyari F, Pichi F, Sen HN, Uy H, Nascimento H, Tugal-Tutkun I, Arevalo JF, Davis J, Thorne J, Hisae Yamamoto J, Smith J, Garweg JG, Biswas J, Babu K, Aggarwal K, Cimino L, Kuffova L, Agarwal M, Zierhut M, Agarwal M, De Smet M, Tognon MS, Errera MH, Munk M, Westcott M, Soheilian M, Accorinti M, Khairallah M, Nguyen M, Kon OM, Mahendradas P, Yang P, Neri P, Ozdal P, Amer R, Lee R, Distia Nora R, Chhabra R, Belfort R, Mehta S, Shoughy S, Luthra S, Mohamed SO, Chee SP, Basu S, Teoh S, Ganesh S, Barisani-Asenbauer T, Guex-Crosier Y, Ozyazgan Y, Akova Y, Habot-Wilner Z, Kempen J, Nguyen QD, Pavesio C, Gupta V; Collaborative Ocular Tuberculosis Study (COTS) Group. Standardization of Nomenclature for Ocular Tuberculosis - Results of Collaborative Ocular Tuberculosis Study (COTS) Workshop. Ocul Immunol Inflamm. 2020 Sep 30;28(sup1):74-84. doi: 10.1080/09273948.2019.1653933. Epub 2019 Dec 10.

Reference Type BACKGROUND
PMID: 31821096 (View on PubMed)

Nussenblatt RB, Peterson JS, Foster CS, Rao NA, See RF, Letko E, Buggage RR. Initial evaluation of subcutaneous daclizumab treatments for noninfectious uveitis: a multicenter noncomparative interventional case series. Ophthalmology. 2005 May;112(5):764-70. doi: 10.1016/j.ophtha.2004.12.034.

Reference Type BACKGROUND
PMID: 15878055 (View on PubMed)

Tugal-Tutkun I, Herbort CP, Khairallah M; Angiography Scoring for Uveitis Working Group (ASUWOG). Scoring of dual fluorescein and ICG inflammatory angiographic signs for the grading of posterior segment inflammation (dual fluorescein and ICG angiographic scoring system for uveitis). Int Ophthalmol. 2010 Oct;30(5):539-52. doi: 10.1007/s10792-008-9263-x. Epub 2008 Sep 16.

Reference Type BACKGROUND
PMID: 18795232 (View on PubMed)

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.

Reference Type RESULT
PMID: 28445659 (View on PubMed)

Song H, Zhao C, Zhang Y, Li D, Qian Y, Gao F, Xiao J, Zhang M. Efficacy and safety of adalimumab for inflammatory flare prevention in paediatric non-infectious anterior uveitis with peripheral retinal vascular leakage: a study protocol for a single-centre, randomised controlled trial. BMJ Open. 2022 Dec 7;12(12):e062211. doi: 10.1136/bmjopen-2022-062211.

Reference Type DERIVED
PMID: 36600374 (View on PubMed)

Other Identifiers

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25-ZS-3062

Identifier Type: -

Identifier Source: org_study_id