Using Aflibercept Injection to Treat Blood Vessel Growth Over the Cornea

NCT01868360 | Terminated Phase 1 DMC

• 1 other identifier: AMB65110
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Corneal Neovascularization

Keywords

cornea; transplant; graft; neovascularization

Outcome Measures

Primary Outcomes (1)

• Safety defined by incidence and severity of adverse events at 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.

  Week 28

Secondary Outcomes (13)

• neovascularization regression

  at time of transplant

• Need for immunosuppression

  Week 28

• Effect on corneal infections

  Through week 28

• Change in visual acuity

  Week 28

• Mean number of injections

  Week 28

Study Arms (2)

Group A subconjunctival aflibercept

EXPERIMENTAL

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.

Drug: Subconjunctival aflibercept

Group B: Standard of care only

PLACEBO COMPARATOR

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

Other: Placebo: Standard of care only

Interventions

Subconjunctival aflibercept DRUG

subconjunctival aflibercept injection

Also known as: EYLEA®, VEGF Trap-Eye

Group A subconjunctival aflibercept

Placebo: Standard of care only OTHER

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

Also known as: Standard of care

Group B: Standard of care only

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Candidates for corneal transplantation (only one eye per patient would be enrolled)
• 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
• Willing and able to comply with clinic visits and study-related procedures
• Provide signed informed consent
• Age 18 or over

You may not qualify if:

• A patient who meets any of the following criteria will be excluded from the study:
• Patients receiving antiangiogenic anti-VEGF medication either systemically or intravitreally for other pathology or have received these drugs within 3 months of study enrollment
• Patients with active corneal infection requiring additional treatment modalities
• Patients receiving coumadin with INR \>2.0, other anti-thrombotic agents (e.g., aspirin, Plavix) permitted at discretion of investigator
• History of cerebrovascular accident or myocardial infarction within 6 months prior to study enrollment
• Uncontrolled blood pressure- defined as SBP\>160 mmHg or DBP \>95mmHg while patient is sitting
• Pregnant or breast-feeding women
• 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.

Sponsors & Collaborators

• Balamurali Ambati: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

John A. Moran Eye Center

Salt Lake City, Utah, 84132, United States

Location

Related Publications (3)

• 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.

  PMID: 1417537 BACKGROUND

• 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.

  PMID: 22898649 BACKGROUND

• 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.

  PMID: 11507336 BACKGROUND

MeSH Terms

Conditions

Corneal Neovascularization; Corneal Diseases; Neovascularization, Pathologic

Interventions

aflibercept; Standard of Care

Condition Hierarchy (Ancestors)

Eye Diseases; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

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

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Ophthalmology

Study Record Dates

• First Submitted: May 15, 2013
• First Posted: June 4, 2013
• Study Start: June 1, 2013
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: October 7, 2015

Record last verified: 2015-10

Locations

US (1)