Effects of Conbercept in Refractory Uveitic Macular Edema and VEGF

Effectiveness of Conbercept in Treating Refractory Uveitic Macular Edema and the Changes of VEGF Levels in the Aqueous Humor

As a primary exploratory study, this study aims to evaluate the short-term effectiveness of intravitreal Conbercept injection in UME, and to explore the correlation between inflammatory factors like VEGF and the responsiveness to treatment.

Study Overview

• Status: Terminated
• Conditions: Uveitis; Macular Edema; Vascular Endothelial Growth Factor; Effect of Drugs
• Intervention / Treatment: Drug: intravitreal injection of Conbercept

Detailed Description

Uveitic macular edema (UME) is one of the commonest and severest complications of chronic uveitis, and is also one of the important causes of permanent vision loss in uveitis. The pathophysiological mechanism of UME remains unclear, but was thought to be caused by damages of internal/external blood-retinal barrier mediated by inflammatory factors, including interleukin-2, interleukin-10, tumor necrosis factor α, prostaglandins and vascular endothelial growth factor (VEGF). Current treatments of UME include local or systemic glucocorticosteroids (GCS), immunosuppressants and biological agents. Although large dose of systemic GCS combined with immunosuppressants lead to quick resolution of ME in most of the cases, UME often relapse with tapering of GCS, and the side effects can be significant. Periocular or intraocular injection of GCS is effective in short term, but repetitive injections often lead to high intraocular pressure and cataract. Intravitreal injection of anti-VEGF agents is a huge advance of medical treatment in ophthalmology in recent years. Since 2007 till now, there have been a number of reports on the effectiveness of intraocular Bevacizumab and Ranibizumab injection in UME, but none about Conbercept. Besides, as the target of anti-VEGF agents, intraocular concentration of VEGF and its changes might be correlated to the sensitivity and responsiveness of UME to anti-VEGF agents, but has not been monitored. As a primary exploratory study, this study aims to evaluate the short-term effectiveness of intravitreal Conbercept injection in UME, and to explore the correlation between inflammatory factors like VEGF and the responsiveness to treatment.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital (PUMCH)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age >= 18 years old
• competent in signing the informed consent
• no severe systemic diseases unrelated to uveitis
• fulfill the criteria of refractory UME

Exclusion Criteria:

• pregnant or preparing pregnancy
• already in other clinical trials
• blood pressure >= 180/110mmHg
• BCVA of the contralateral eye <= 20/200
• cardiovascular events within 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: refractory UME patients treated with Conbercept; patients in this arm should meet the inclusion criteria and the definition of refractory UME	Drug: intravitreal injection of Conbercept; patients will receive intravitreal injection of Conbercept, and at the same time, aqueous humor sample will be obtained from the anterior chamber to measure the concentrations of cytokines.; Other Names: Lumitin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of best corrected visual acuity (BCVA)	changes from baseline BCVA at 1, 2, 3, 4, 5, 6 months after injection (at each follow-up visit)	baseline and at 1, 2, 3, 4, 5, 6 months after injection
Changes of central retinal thickness (CRT)	changes from baseline CRT at 1, 2, 3, 4, 5, 6 months after injection (at each follow-up visit)	baseline and at 1, 2, 3, 4, 5, 6 months after injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes of concentration of inflammatory cytokines	inflammatory cytokines include VEGF-A, VEGF-B, interleukin (IL)-2, interleukin-6, interleukin-8, interleukin-10, interleukin-12, tumor necrosis factor (TNF) α, monocyte chemotactic protein-1 and macrophage inflammatory protein-1	before injection (baseline), 1 month after the first injection, at the end of the study (6 months)
inflammatory status	changes from baseline flare and cells in the anterior chamber at 1, 2, 3, 4, 5, 6 months after injection	baseline and at 1, 2, 3, 4, 5, 6 months after injection
side effects of the eye: increase of intraocular pressure	changes from baseline intraocular pressure at 1, 2, 3, 4, 5, 6 months after injection	baseline and at 1, 2, 3, 4, 5, 6 months after injection
side effects of the eye: development/exacerbation of cataract	whether cataract is developed or exacerbated	baseline and at 1, 2, 3, 4, 5, 6 months after injection

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Beijing Bethune public welfare fund

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2019
• Primary Completion (Actual): April 12, 2020
• Study Completion (Actual): February 12, 2022

Study Registration Dates

• First Submitted: January 1, 2020
• First Submitted That Met QC Criteria: March 4, 2020
• First Posted (Actual): March 5, 2020

Study Record Updates

• Last Update Posted (Actual): October 25, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Uveitis; Macular Edema; vascular endothelial growth factor; aqueous humor; Effect of Drugs
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Uveal Diseases; Macular Degeneration; Macular Edema; Edema; Uveitis
• Other Study ID Numbers: BJ-LM2018010J

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No