Corneal NeovascularizationPhase 1NCT01868360
Using Aflibercept Injection to Treat Blood Vessel Growth Over the Cornea
A Phase 1 study testing Subconjunctival aflibercept in people with Corneal Neovascularization, run by Balamurali Ambati at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Corneal Neovascularization
- What is being tested?
- Subconjunctival aflibercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2013to Oct 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
John A. Moran Eye Center
Salt Lake City, Utah, 84132
About this study
Official title: Subconjunctival Aflibercept Injection for Corneal Neovascularization
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.
Read the 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
- Being tested
- Subconjunctival aflibercept, Placebo: Standard of care only
- Keywords
- cornea, transplant, graft, neovascularization
- Medical subject headings
- Corneal Neovascularization, Corneal Diseases, Neovascularization, Pathologic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Subconjunctival afliberceptDrug
Also called EYLEA®, VEGF Trap-Eye
subconjunctival aflibercept injection
Placebo: Standard of care onlyOther
Also called Standard of care
Patients will receive standard of care (steroids and cyclosporine) treatment only.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Subconjunctival aflibercept |
| Group B: Standard of care only | Placebo comparator | Patients will receive standard of care (steroids and cyclosporine) treatment only. Receives: Other: Placebo: Standard of care only |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 28
Secondary outcomes (13)
neovascularization regression
Ability of subconjunctival aflibercept injection to regress neovascularization at time of transplant and promote graft survival after corneal transplantation
Measured: at time of transplant
Need for immunosuppression
Need for immunosuppression at week 28 in both treatment groups
Measured: Week 28
Effect on corneal infections
Effect on corneal infections or other side effects through week 28 in both treatment groups
Measured: Through week 28
Change in visual acuity
Change in ETDRS visual acuity from baseline at week 28 in both treatment groups
Measured: Week 28
Mean number of injections
Mean number of injections performed per patient through week 28 in patients receiving subconjunctival aflibercept injections
Measured: Week 28
Rescue therapy
Need for rescue treatment in the standard of care group through week 28
Measured: Week 28
neovascularization regression
Ability of subconjunctival aflibercept injection to regress neovascularization (at 28 weeks after transplant) and promote graft survival after corneal transplantation
Measured: at 28 weeks after transplant
neovascularization regression
Ability of subconjunctival aflibercept injection to regress neovascularization at 52 weeks after transplant and promote graft survival after corneal transplantation
Measured: at 52 weeks after transplantation
Need for immunosuppression
need for immunosuppression at week 52 in both treatment groups
Measured: week 52
Effect on corneal infections
Effect on corneal infections or other side effects through week 52 in both treatment groups.
Measured: Through week 52
Change in visual acuity
Change in ETDRS visual acuity from baseline at week 52 in both treatment groups
Measured: Week 52
Mean number of injections
Mean number of injections performed per patient through week 52 in patients receiving subconjunctival aflibercept injections
Measured: Week 52
Rescue therapy
Need for rescue treatment in the standard of care group through week 52
Measured: Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2013 (estimated)
- Study startJun 2013
- Primary completionOct 2015
- Study completionOct 2015
Why it stopped: Lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Corneal NeovascularizationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Balamurali Ambati
- Sponsor type
- University, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor-investigator, Balamurali Ambati, University of Utah
- Investigators
- Balamurali Ambati, M.D., Ph.D., M.B.A., Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01868360
- Sponsor's protocol ID
- AMB65110
- Status last verified
- Oct 2015
- First submitted
- 15 May 2013
- Last updated
- 7 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 1417537Chang 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.
PubMed 22898649Chang JH, Gabison EE, Kato T, Azar DT. Corneal neovascularization. Curr Opin Ophthalmol. 2001 Aug;12(4):242-9. doi: 10.1097/00055735-200108000-00002.
PubMed 11507336
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Subconjunctival Aflibercept Injection for Corneal Neovascularization
- ClinicalTrials.gov ID
- NCT01868360
- Acronym / sponsor ID
- AMB65110
- Conditions
- Corneal Neovascularization
- Keywords
- cornea, transplant, graft, neovascularization
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Balamurali AmbatiUniversity, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- Jun 2013
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 4 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A subconjunctival aflibercept | Experimental | Drug: Subconjunctival afliberceptPatients 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 B: Standard of care only | Placebo comparator | Other: Placebo: Standard of care onlyPatients will receive standard of care (steroids and cyclosporine) treatment only. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Subconjunctival afliberceptAlso: EYLEA®, VEGF Trap-Eyesubconjunctival aflibercept injection | Drug | Group A subconjunctival aflibercept |
| Placebo: Standard of care onlyAlso: Standard of carePatients will receive standard of care (steroids and cyclosporine) treatment only. | Other | Group B: Standard of care only |
Primary outcome
Safety defined by incidence and severity of adverse events at week 28
Time frame: 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.
13 secondary outcomes
neovascularization regression
Time frame: at time of transplant
Need for immunosuppression
Time frame: Week 28
Effect on corneal infections
Time frame: Through week 28
Change in visual acuity
Time frame: Week 28
Mean number of injections
Time frame: Week 28
Rescue therapy
Time frame: Week 28
neovascularization regression
Time frame: at 28 weeks after transplant
neovascularization regression
Time frame: at 52 weeks after transplantation
Need for immunosuppression
Time frame: week 52
Effect on corneal infections
Time frame: Through week 52
Change in visual acuity
Time frame: Week 52
Mean number of injections
Time frame: Week 52
Rescue therapy
Time frame: Week 52
Results and safety
The study was stopped early (reason given: Lack of enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2015.
- Background: PubMed 1417537The 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.
- Background: PubMed 22898649Chang 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.
- Background: PubMed 11507336Chang JH, Gabison EE, Kato T, Azar DT. Corneal neovascularization. Curr Opin Ophthalmol. 2001 Aug;12(4):242-9. doi: 10.1097/00055735-200108000-00002.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Balamurali Ambati, M.D., Ph.D., M.B.A. principal investigator
University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Subconjunctival aflibercept in people with Corneal Neovascularization, run by Balamurali Ambati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety defined by incidence and severity of adverse events at week 28 (time frame: Week 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01868360, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2015.