Clinical Trial: Using Aflibercept Injection to Treat Blood Vessel Growth Over the Cornea

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Subconjunctival Aflibercept Injection for Corneal Neovascularization

Brief Summary:

The cornea is the clear front part of the eye. Corneal neovascularization, the excessive growth of blood vessels into the cornea, is a sight-threatening condition. Corneal neovascularization is also a well recognized risk factor for corneal graft failure. The current standard of care to prevent graft rejection includes use of topical steroids and medicines that suppress the immune system. These medicines do not address corneal neovascularization. The purpose of the study is to establish the safety and potential efficacy of subconjunctival injections of aflibercept (EYLEA® , marketed by Regeneron) injection in inducing regression of blood vessels growing into the cornea and promoting graft survival.

This study is being conducted by Dr. Balamurali Ambati at the Moran Eye Center.


Detailed Summary:

Corneal neovascularization is a sight threatening condition and is also a well recognized risk factor for corneal graft failure. Current standard of care to prevent graft rejection includes use of topical steroids and immunosuppressants. These do not address corneal neovascularization. The cornea is kept in its avascular state by a complex interaction of signal proteins and host receptors, with a vital role played by the soluble VEGF-receptor 1. In any condition of chronic corneal inflammation or hypoxia, the balance may tip in favour of pro-angiogenic factors, and neovascularization will ensue. Early and limited studies have examined the effect of subconjunctival or intracorneal administration of monoclonal antibodies to VEGF (bevacizumab, ranibizumab) in combating corneal neovascularization. Most report subtotal or temporary regression. The development of aflibercept (also known as VEGF Trap-Eye) offers new hope of more effectively combating the problem. In this study, research will be conducted to investigate and assess safety of subconjunctival aflibercept injection in patients with corneal neovascularization undergoing corneal transplantation.

This is a phase 1, prospective, randomized, open label clinical trial that will enroll 10 corneal transplant patients with corneal neovascularization in one or more quadrants crossing more than 0.5 mm over the limbus at the time of corneal transplantation.


Sponsor: Balamurali Ambati

Current Primary Outcome: Safety defined by incidence and severity of adverse events at week 28 [ Time Frame: Week 28 ]

The primary endpoint in the study is safety as defined by incidence and severity of adverse events in patients with corneal neovascularization undergoing corneal transplant.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • neovascularization regression [ Time Frame: at time of transplant ]
    Ability of subconjunctival aflibercept injection to regress neovascularization at time of transplant and promote graft survival after corneal transplantation
  • Need for immunosuppression [ Time Frame: Week 28 ]
    Need for immunosuppression at week 28 in both treatment groups
  • Effect on corneal infections [ Time Frame: Through week 28 ]
    Effect on corneal infections or other side effects through week 28 in both treatment groups
  • Change in visual acuity [ Time Frame: Week 28 ]
    Change in ETDRS visual acuity from baseline at week 28 in both treatment groups
  • Mean number of injections [ Time Frame: Week 28 ]
    Mean number of injections performed per patient through week 28 in patients receiving subconjunctival aflibercept injections
  • Rescue therapy [ Time Frame: Week 28 ]
    Need for rescue treatment in the standard of care group through week 28
  • neovascularization regression [ Time Frame: at 28 weeks after transplant ]
    Ability of subconjunctival aflibercept injection to regress neovascularization (at 28 weeks after transplant) and promote graft survival after corneal transplantation
  • neovascularization regression [ Time Frame: at 52 weeks after transplantation ]
    Ability of subconjunctival aflibercept injection to regress neovascularization at 52 weeks after transplant and promote graft survival after corneal transplantation
  • Need for immunosuppression [ Time Frame: week 52 ]
    need for immunosuppression at week 52 in both treatment groups
  • Effect on corneal infections [ Time Frame: Through week 52 ]
    Effect on corneal infections or other side effects through week 52 in both treatment groups.
  • Change in visual acuity [ Time Frame: Week 52 ]
    Change in ETDRS visual acuity from baseline at week 52 in both treatment groups
  • Mean number of injections [ Time Frame: Week 52 ]
    Mean number of injections performed per patient through week 52 in patients receiving subconjunctival aflibercept injections
  • Rescue therapy [ Time Frame: Week 52 ]
    Need for rescue treatment in the standard of care group through week 52


Original Secondary Outcome: Same as current

Information By: University of Utah

Dates:
Date Received: May 15, 2013
Date Started: June 2013
Date Completion:
Last Updated: October 5, 2015
Last Verified: October 2015