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

NCT05015335 | Unknown Phase 4 FDA Drug

• 1 other identifier: 25-ZS-3062
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Uveitis, Anterior; Adalimumab

Keywords

pheripheral retinal vasuclar leakage; adalimumab; methotrexate

Outcome Measures

Primary Outcomes (1)

• Uveitis flare

  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

  At 6 months' follow-up visit

Secondary Outcomes (7)

• Extent of peripheral vascular leakage

  At 6 months' follow-up visit

• Keratic precipitates

  At 6 months' follow-up visit

• Vitreous haze

  At 6 months' follow-up visit

• Best corrected visual acuity (BCVA)

  At 6 months' follow-up visit

• Adverse events

  through study completion, an average of 6 months

Study Arms (2)

Adalimumab

EXPERIMENTAL

Adalimumab administered subcutaneously at 40mg every 2 weeks

Drug: Adalimumab

Methotrexate

ACTIVE COMPARATOR

Methotrexate given 10mg orally once a week.

Drug: Methotrexate

Interventions

Adalimumab DRUG

ADA 40mg q2w

Also known as: ADA

Adalimumab

Methotrexate DRUG

MTX 10mg qw

Also known as: MTX

Methotrexate

Eligibility Criteria

• Age: 4 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children with noninfectious uveitis aged between 4-16, weight ≥ 30kg.
• 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

You may not qualify if:

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

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking University Medical College Hospital

Beijing, 100000, China

RECRUITING

Related Publications (5)

• 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.

  PMID: 31821096 BACKGROUND

• 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.

  PMID: 15878055 BACKGROUND

• 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.

  PMID: 18795232 BACKGROUND

• 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 RESULT

• 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.

  PMID: 36600374 DERIVED

MeSH Terms

Conditions

Uveitis, Anterior

Interventions

Adalimumab; Methotrexate

Condition Hierarchy (Ancestors)

Panuveitis; Uveitis; Uveal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Meifen Zhang, MD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hang Song, MD

CONTACT

+86 15600612346; songhang_pumch@163.com

Meifen Zhang, MD

CONTACT

+86 13681566748; meifen_zhang@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 10, 2021
• First Posted: August 20, 2021
• Study Start: August 19, 2021
• Primary Completion: July 1, 2022
• Study Completion: July 1, 2023
• Last Updated: November 10, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)