Using Aflibercept Injection to Treat Blood Vessel Growth Over the Cornea

NCT ID: NCT01868360

Last Updated: 2015-10-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2015-10-31

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.

Conditions

Corneal Neovascularization

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A subconjunctival aflibercept

Patients will receive 2mg (0.05mL) subconjunctival aflibercept injection in addition to standard of care treatment (steroids and cyclosporine). Patients will receive one injection four weeks (+/- 1 week) prior to transplantation. They will receive a second injection at the conclusion of corneal transplantation.

Patients may receive as-needed repeat injections (minimum of 30 days in between treatments) for recurrence of corneal neovascularization (defined as >1.0 mm crossing onto the cornea, past the limbus, or extension of vessels beyond previously documented extent) during the follow-up period.

Group Type: EXPERIMENTAL

Subconjunctival aflibercept

Intervention Type: DRUG

subconjunctival aflibercept injection

Group B: Standard of care only

Patients will receive standard of care (steroids and cyclosporine) treatment only.

Group Type: PLACEBO_COMPARATOR

Placebo: Standard of care only

Intervention Type: OTHER

Patients will receive standard of care (steroids and cyclosporine) treatment only.

Interventions

Subconjunctival aflibercept

subconjunctival aflibercept injection

Intervention Type: DRUG

Placebo: Standard of care only

Patients will receive standard of care (steroids and cyclosporine) treatment only.

Intervention Type: OTHER

Other Intervention Names

EYLEA®; VEGF Trap-Eye; Standard of care

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Balamurali Ambati

OTHER

Sponsor Role: lead

Responsible Party

Balamurali Ambati

Professor of Ophthalmology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Balamurali Ambati, M.D., Ph.D., M.B.A.

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

John A. Moran Eye Center

Salt Lake City, Utah, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 1417537 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22898649 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11507336 (View on PubMed)

Other Identifiers

AMB65110

Identifier Type: -

Identifier Source: org_study_id