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Using Aflibercept Injection to Treat Blood Vessel Growth Over the Cornea

Primary Purpose

Corneal Neovascularization

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Subconjunctival aflibercept

Placebo: Standard of care only

About this trial

This is an interventional treatment trial for Corneal Neovascularization focused on measuring cornea, transplant, graft, neovascularization

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

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

Exclusion Criteria:

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.

Sites / Locations

John A. Moran Eye Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Group A subconjunctival aflibercept

Group B: Standard of care only

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

neovascularization regression

Ability of subconjunctival aflibercept injection to regress neovascularization at time of transplant and promote graft survival after corneal transplantation

Need for immunosuppression

Need for immunosuppression at week 28 in both treatment groups

Effect on corneal infections

Effect on corneal infections or other side effects through week 28 in both treatment groups

Change in visual acuity

Change in ETDRS visual acuity from baseline at week 28 in both treatment groups

Mean number of injections

Mean number of injections performed per patient through week 28 in patients receiving subconjunctival aflibercept injections

Rescue therapy

Need for rescue treatment in the standard of care group through week 28

neovascularization regression

Ability of subconjunctival aflibercept injection to regress neovascularization (at 28 weeks after transplant) and promote graft survival after corneal transplantation

neovascularization regression

Ability of subconjunctival aflibercept injection to regress neovascularization at 52 weeks after transplant and promote graft survival after corneal transplantation

Need for immunosuppression

need for immunosuppression at week 52 in both treatment groups

Effect on corneal infections

Effect on corneal infections or other side effects through week 52 in both treatment groups.

Change in visual acuity

Change in ETDRS visual acuity from baseline at week 52 in both treatment groups

Mean number of injections

Mean number of injections performed per patient through week 52 in patients receiving subconjunctival aflibercept injections

Rescue therapy

Need for rescue treatment in the standard of care group through week 52

Full Information

NCT ID

NCT01868360

First Posted

May 15, 2013

Last Updated

October 5, 2015

Sponsor

Balamurali Ambati

Collaborators

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01868360

Brief Title

Using Aflibercept Injection to Treat Blood Vessel Growth Over the Cornea

Official Title

Subconjunctival Aflibercept Injection for Corneal Neovascularization

Study Type

Interventional

2. Study Status

Record Verification Date

October 2015

Overall Recruitment Status

Terminated

Why Stopped

Lack of enrollment

Study Start Date

June 2013 (undefined)

Primary Completion Date

October 2015 (Actual)

Study Completion Date

October 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Balamurali Ambati

Collaborators

Regeneron Pharmaceuticals

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Corneal Neovascularization

Keywords

cornea, transplant, graft, neovascularization

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

2 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group A subconjunctival aflibercept

Arm Type

Experimental

Arm Description

Arm Title

Group B: Standard of care only

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Subconjunctival aflibercept

Other Intervention Name(s)

EYLEA®, VEGF Trap-Eye

Intervention Description

subconjunctival aflibercept injection

Intervention Type

Other

Intervention Name(s)

Placebo: Standard of care only

Other Intervention Name(s)

Standard of care

Intervention Description

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

Primary Outcome Measure Information:

Title

Safety defined by incidence and severity of adverse events at week 28

Description

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.

Time Frame

Week 28

Secondary Outcome Measure Information:

Title

neovascularization regression

Description

Ability of subconjunctival aflibercept injection to regress neovascularization at time of transplant and promote graft survival after corneal transplantation

Time Frame

at time of transplant

Title

Need for immunosuppression

Description

Need for immunosuppression at week 28 in both treatment groups

Time Frame

Week 28

Title

Effect on corneal infections

Description

Effect on corneal infections or other side effects through week 28 in both treatment groups

Time Frame

Through week 28

Title

Change in visual acuity

Description

Change in ETDRS visual acuity from baseline at week 28 in both treatment groups

Time Frame

Week 28

Title

Mean number of injections

Description

Mean number of injections performed per patient through week 28 in patients receiving subconjunctival aflibercept injections

Time Frame

Week 28

Title

Rescue therapy

Description

Need for rescue treatment in the standard of care group through week 28

Time Frame

Week 28

Title

neovascularization regression

Description

Ability of subconjunctival aflibercept injection to regress neovascularization (at 28 weeks after transplant) and promote graft survival after corneal transplantation

Time Frame

at 28 weeks after transplant

Title

neovascularization regression

Description

Ability of subconjunctival aflibercept injection to regress neovascularization at 52 weeks after transplant and promote graft survival after corneal transplantation

Time Frame

at 52 weeks after transplantation

Title

Need for immunosuppression

Description

need for immunosuppression at week 52 in both treatment groups

Time Frame

week 52

Title

Effect on corneal infections

Description

Effect on corneal infections or other side effects through week 52 in both treatment groups.

Time Frame

Through week 52

Title

Change in visual acuity

Description

Change in ETDRS visual acuity from baseline at week 52 in both treatment groups

Time Frame

Week 52

Title

Mean number of injections

Description

Mean number of injections performed per patient through week 52 in patients receiving subconjunctival aflibercept injections

Time Frame

Week 52

Title

Rescue therapy

Description

Need for rescue treatment in the standard of care group through week 52

Time Frame

Week 52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: A patient must meet the following criteria to be eligible for inclusion in the study: 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 Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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

Organizational Affiliation

University of Utah

Official's Role

Principal Investigator

Facility Information:

Facility Name

John A. Moran Eye Center

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84132

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

1417537

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.

Results Reference

background

PubMed Identifier

22898649

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.

Results Reference

background

PubMed Identifier

11507336

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.

Results Reference

background

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Using Aflibercept Injection to Treat Blood Vessel Growth Over the Cornea

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