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Using Aflibercept Injection to Treat Blood Vessel Growth Over the Cornea

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Utah
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Balamurali Ambati, University of Utah
ClinicalTrials.gov Identifier:
NCT01868360
First received: May 15, 2013
Last updated: June 24, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Corneal Neovascularization
Drug: Subconjunctival aflibercept
Other: Placebo: Standard of care only
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Subconjunctival Aflibercept Injection for Corneal Neovascularization

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • Safety defined by incidence and severity of adverse events at week 28 [ Time Frame: Week 28 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: at time of transplant ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Need for immunosuppression at week 28 in both treatment groups

  • Effect on corneal infections [ Time Frame: Through week 28 ] [ Designated as safety issue: No ]
    Effect on corneal infections or other side effects through week 28 in both treatment groups

  • Change in visual acuity [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
    Change in ETDRS visual acuity from baseline at week 28 in both treatment groups

  • Mean number of injections [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
    Mean number of injections performed per patient through week 28 in patients receiving subconjunctival aflibercept injections

  • Rescue therapy [ Time Frame: Week 28 ] [ Designated as safety issue: Yes ]
    Need for rescue treatment in the standard of care group through week 28

  • neovascularization regression [ Time Frame: at 28 weeks after transplant ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    need for immunosuppression at week 52 in both treatment groups

  • Effect on corneal infections [ Time Frame: Through week 52 ] [ Designated as safety issue: No ]
    Effect on corneal infections or other side effects through week 52 in both treatment groups.

  • Change in visual acuity [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    Change in ETDRS visual acuity from baseline at week 52 in both treatment groups

  • Mean number of injections [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    Mean number of injections performed per patient through week 52 in patients receiving subconjunctival aflibercept injections

  • Rescue therapy [ Time Frame: Week 52 ] [ Designated as safety issue: Yes ]
    Need for rescue treatment in the standard of care group through week 52


Estimated Enrollment: 10
Study Start Date: June 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: Subconjunctival aflibercept
subconjunctival aflibercept injection
Other Names:
  • EYLEA®
  • VEGF Trap-Eye
Placebo Comparator: Group B: Standard of care only
Patients will receive standard of care (steroids and cyclosporine) treatment only.
Other: Placebo: Standard of care only
Patients will receive standard of care (steroids and cyclosporine) treatment only.
Other Name: Standard of care

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01868360

Contacts
Contact: Bala Ambati, M.D. Ph.D. M.B.A. (801) 581-2352 bala.ambati@utah.edu

Locations
United States, Utah
John A. Moran Eye Center Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Deborah Harrison, M.S.    (801) 585-6645    deborah.harrison@hsc.utah.edu   
Principal Investigator: Balamurali Ambati, M.D. Ph.D. M.B.A.         
Sponsors and Collaborators
Balamurali Ambati
Regeneron Pharmaceuticals
Investigators
Principal Investigator: Balamurali Ambati, M.D., Ph.D., M.B.A. University of Utah
  More Information

Publications:
Responsible Party: Balamurali Ambati, Professor of Ophthalmology, University of Utah
ClinicalTrials.gov Identifier: NCT01868360     History of Changes
Other Study ID Numbers: AMB65110
Study First Received: May 15, 2013
Last Updated: June 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Utah:
cornea
transplant
graft
neovascularization

Additional relevant MeSH terms:
Corneal Neovascularization
Neovascularization, Pathologic
Corneal Diseases
Eye Diseases
Metaplasia
Pathologic Processes

ClinicalTrials.gov processed this record on November 27, 2014