Clinical trial NCT01868360: Using Aflibercept Injection to Treat Blood Vessel Growth Over the Cornea
Official title: Subconjunctival Aflibercept Injection for Corneal Neovascularization
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Corneal Neovascularization
Keywords: cornea
transplant
graft
neovascularization
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2013-06-04
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 description: 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.

Eligibility criteria: Inclusion Criteria:

A patient must meet the following criteria to be eligible for inclusion in the study:

1. Candidates for corneal transplantation (only one eye per patient would be enrolled)
2. Patients with corneal neovascularization in one or more quadrants crossing more than 1.0 mm over the limbus at time of enrollment in the study
3. Willing and able to comply with clinic visits and study-related procedures
4. Provide signed informed consent
5. Age 18 or over

Exclusion Criteria:

A patient who meets any of the following criteria will be excluded from the study:

1. Patients receiving antiangiogenic anti-VEGF medication either systemically or intravitreally for other pathology or have received these drugs within 3 months of study enrollment
2. Patients with active corneal infection requiring additional treatment modalities
3. Patients receiving coumadin with INR \>2.0, other anti-thrombotic agents (e.g., aspirin, Plavix) permitted at discretion of investigator
4. History of cerebrovascular accident or myocardial infarction within 6 months prior to study enrollment
5. Uncontrolled blood pressure- defined as SBP\>160 mmHg or DBP \>95mmHg while patient is sitting
6. Pregnant or breast-feeding women
7. Sexually active men\* or women of childbearing potential\*\* who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device \[IUD\]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly) \*Contraception is not required for men with documented vasectomy. \*\*Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

Primary outcomes:
measure: Safety defined by incidence and severity of adverse events at week 28
timeFrame: Week 28
Secondary outcomes:
measure: neovascularization regression
timeFrame: at time of transplant
measure: Need for immunosuppression
timeFrame: Week 28
measure: Effect on corneal infections
timeFrame: Through week 28
measure: Change in visual acuity
timeFrame: Week 28
measure: Mean number of injections
timeFrame: Week 28
measure: Rescue therapy
timeFrame: Week 28
measure: neovascularization regression
timeFrame: at 28 weeks after transplant
measure: neovascularization regression
timeFrame: at 52 weeks after transplantation
measure: Need for immunosuppression
timeFrame: week 52
measure: Effect on corneal infections
timeFrame: Through week 52
measure: Change in visual acuity
timeFrame: Week 52
measure: Mean number of injections
timeFrame: Week 52
measure: Rescue therapy
timeFrame: Week 52
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: John A. Moran Eye Center
state: Utah
Study officials:
affiliation: University of Utah
name: Balamurali Ambati, M.D., Ph.D., M.B.A.
role: PRINCIPAL_INVESTIGATOR
References:
citation: The collaborative corneal transplantation studies (CCTS). Effectiveness of histocompatibility matching in high-risk corneal transplantation. The Collaborative Corneal Transplantation Studies Research Group. Arch Ophthalmol. 1992 Oct;110(10):1392-403.
citation: Chang JH, Garg NK, Lunde E, Han KY, Jain S, Azar DT. Corneal neovascularization: an anti-VEGF therapy review. Surv Ophthalmol. 2012 Sep;57(5):415-29. doi: 10.1016/j.survophthal.2012.01.007.
citation: Chang JH, Gabison EE, Kato T, Azar DT. Corneal neovascularization. Curr Opin Ophthalmol. 2001 Aug;12(4):242-9. doi: 10.1097/00055735-200108000-00002.