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

November 2, 2021 updated by: Peking Union Medical College Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Beijing, China, 100000
        • Recruiting
        • Peking University Medical College Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years to 16 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Adalimumab
Adalimumab administered subcutaneously at 40mg every 2 weeks
Drug: Adalimumab
ADA 40mg q2w
Other Names:
  • ADA
Active Comparator: Methotrexate
Methotrexate given 10mg orally once a week.
Drug: Methotrexate
MTX 10mg qw
Other Names:
  • MTX

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Uveitis flare
Time Frame: 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
At 6 months' follow-up visit

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Extent of peripheral vascular leakage
Time Frame: 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.
At 6 months' follow-up visit
Keratic precipitates
Time Frame: At 6 months' follow-up visit
Keratic precipitates was recorded in a dichotomous method.
At 6 months' follow-up visit
Vitreous haze
Time Frame: 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.
At 6 months' follow-up visit
Best corrected visual acuity (BCVA)
Time Frame: At 6 months' follow-up visit
BCVA was transformed into logMar form
At 6 months' follow-up visit
Adverse events
Time Frame: through study completion, an average of 6 months
Adverse events included the infectious events and laboratory parameter abnormalities.
through study completion, an average of 6 months
frequency of topical steroid eyedrops if any inflammatory flare happens.
Time Frame: At 6 months' follow-up visit
Different GCs eye drops are transformed into equivalent 1% prednisolone for analysis.
At 6 months' follow-up visit
Systemic immunomodulatory therapy (sIMT, including GCs and immunosuppressive drugs)load at the 6-month follow-up visit if any inflammatory flare ever happens.
Time Frame: At 6 months' follow-up visit
sIMT load is transformed into a quantizable score based on prior studies in uveitis.
At 6 months' follow-up visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Investigators

  • Principal Investigator: Meifen Zhang, MD, Peking Union Medical College Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 19, 2021

Primary Completion (Anticipated)

July 1, 2022

Study Completion (Anticipated)

July 1, 2023

Study Registration Dates

First Submitted

August 10, 2021

First Submitted That Met QC Criteria

August 15, 2021

First Posted (Actual)

August 20, 2021

Study Record Updates

Last Update Posted (Actual)

November 10, 2021

Last Update Submitted That Met QC Criteria

November 2, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 25-ZS-3062

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

If other researcher needs the IPD. Please contact songhang_pumch@163.com

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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