Corneal NeovascularizationPhase 1/2NCT01072357
Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival
A Phase 1/2 study testing Avastin® (bevacizumab) and 0.9% NaCl & Refresh Liquigel in people with Corneal Neovascularization and Corneal Graft Failure, run by Reza Dana, MD at 1 site in United States.
Trial summary
The leading risk factor for corneal transplant rejection is abnormal blood vessel growth of the host bed. Vascular endothelial growth factor (VEGF) is thought to be a mediator of this corneal neovascularization (NV), therefore we would like to test the safety and efficacy of local VEGF blockade in the promotion of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Corneal Neovascularization, Corneal Graft Failure
- What is being tested?
- Avastin® (bevacizumab) and 0.9% NaCl & Refresh Liquigel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2009to Jan 2015
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Age > 18 years
- Patient or legally authorized representative willing and able to provide written informed consent
- Willing and able to comply with study assessments for the full duration of the study
- High-risk characteristics for penetrating keratoplasty: Either presence of 1.) Corneal NV in one or more quadrants (≥ 3 clock hours NV ≥ 2mm from the limbus) OR 2.) Extension of corneal NV to graft-host junction in a previous failed graft
- In generally good stable overall health
Who cannot join
- History of Stevens-Johnson syndrome or ocular pemphigoid
- Ocular or periocular malignancy
- Non-healing epithelial defect of at least 0.5x0.5 mm in host corneal bed lasting ≥6 weeks preoperatively
- Uncontrolled glaucoma
- Currently on dialysis
- Has received treatment with anti-VEGF agents (intraocular or systemic) within 45 days of study entry
Show all 14Show fewer
- Concurrent use of systemic anti-VEGF agents
- Change in topical corticosteroid regimen within 14 days of transplantation
- Use of systemic immunosuppressive for indication other than corneal graft rejection
- Pregnancy (positive pregnancy test) or lactating
- Pre-menopausal women not using adequate contraception (Reliable intrauterine devices, hormonal contraception or a spermicide in combination with a barrier method)
- Uncontrolled hypertension defined as systolic blood pressure (BP) ≥150 or diastolic BP ≥90 mmHg
- History of thromboembolic event within 12 months prior to study entry
- Participation in another simultaneous medical investigation or trial
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, 02114
About this study
The leading risk factor for corneal transplant rejection is abnormal blood vessel growth of the host bed. Vascular endothelial growth factor (VEGF) is thought to be a mediator of this corneal neovascularization (NV), therefore we would like to test the safety and efficacy of local VEGF blockade in the promotion of graft survival in high risk corneal transplants.
Read the detailed description
The purpose of this study is to test the effectiveness of a drug, bevacizumab (Avastin), in preventing blood vessels that often occur after a corneal transplantation which are considered at "high-risk" for rejection. In many cases these blood vessels lead to the graft rejection and eventual failure of the corneal transplant. It is hoped that this treatment will increase the chances of corneal graft survival.
The medication used in this study is called bevacizumab or Avastin (Genentech, Inc). It works by inhibiting the action of a molecule called vascular endothelial growth factor (VEGF). VEGF is a substance molecule that binds to certain cells to stimulate new blood vessel formation. When VEGF is bound to the drug, it cannot stimulate the formation and growth of new blood vessels. Growth of blood vessels into the cornea is a complication which can worsen the prognosis of your corneal transplant and put the transplant at a higher risk for rejection.
- Conditions
- Corneal Neovascularization, Corneal Graft Failure
- Being tested
- Avastin® (bevacizumab), 0.9% NaCl & Refresh Liquigel
- Keywords
- High-Risk Corneal Transplantation, Penetrating Keratoplasty, Neovascularization, Corneal Blood Vessels, Avastin, Bevacizumab, Corneal Graft
- Medical subject headings
- Corneal Neovascularization, Neovascularization, Pathologic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Avastin® (bevacizumab)Drug
Also called Avastin, bevacizumab
One time subconjunctival injection of 0.1 mL (2.5 mg) bevacizumab followed by topical treatment with 1% solution bevacizumab four times a day for four weeks.
0.9% NaCl & Refresh LiquigelDrug
Also called Sodium Chloride, Refresh Liquigel, NaCL
One-time subconjunctival injection of 0.1mL 0.9% NaCl followed by topical treatment with Refresh Liquigel four times a day for four weeks
| Study group | Role | What they receive |
|---|---|---|
| Avastin® (bevacizumab) | Active comparator | Treatment will begin on Day 0, immediately upon the conclusion of the penetrating keratoplasty procedure with an injection of 0.1 milliliter (mL) (2.5 mg) bevacizumab. Starting Day 1 post-transplant surgery, subjects will begin treatment with topical bevacizumab (1% solution). Topical treatment will be self-administered 4 times a day for 4 weeks.
The study treatments are to be given in addition to standard of care treatments. Also, all patients will follow a standard post-operative follow-up visit schedule. Receives: Drug: Avastin® (bevacizumab) |
| 0.9% NaCl & Refresh Liquigel | Placebo comparator | Treatment will begin on Day 0, immediately upon the conclusion of the penetrating keratoplasty procedure with an injection of 0.1 mL 0.9% sodium chloride (NaCl). Starting Day 1 post-transplant surgery, subjects will begin treatment with topical Refresh Liquigel. Topical treatment will be self-administered 4 times a day for 4 weeks.
The study treatments (both topical and subconjunctival injection) are to be given in addition to standard of care treatments. Also, all patients will follow a standard post-operative follow-up visit schedule. Receives: Drug: 0.9% NaCl & Refresh Liquigel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Graft Failure at Week 39 and 52
Time from surgery to overall graft failure (regardless of cause). Graft failure was monitored throughout the entire study, but only the time points at which graft failure occurred are reported below.
Measured: 12 months
Secondary outcomes (1)
Endothelial Cell Density
Endothelial Cell Density (Assessed at Weeks 26 \& 52). Measure of the number of cells present within the endothelium that are responsible for providing the cornea with nourishment.
Measured: 52 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2010 (estimated)
- Study startDec 2009
- Primary completionJan 2015
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Reza Dana, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Reza Dana, MD, Massachusetts Eye and Ear Infirmary
- Investigators
- Reza Dana, MD, MPH, MSc, Principal investigator, Massachusetts Eye and Ear Infirmary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01072357
- Sponsor's protocol ID
- 09-07-062
- Status last verified
- May 2018
- First submitted
- 18 Feb 2010
- Last updated
- 15 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Bevacizumab in High-Risk Corneal Transplant Survival
- ClinicalTrials.gov ID
- NCT01072357
- Acronym / sponsor ID
- 09-07-062
- Conditions
- Corneal Neovascularization, Corneal Graft Failure
- Keywords
- High-Risk Corneal Transplantation, Penetrating Keratoplasty, Neovascularization, Corneal Blood Vessels, Avastin, Bevacizumab, Corneal Graft
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Reza Dana, MDUniversity, hospital or other
- Study start
- Dec 2009
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 22 Feb 2010 (estimated)
- Results
- Posted 15 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The leading risk factor for corneal transplant rejection is abnormal blood vessel growth of the host bed. Vascular endothelial growth factor (VEGF) is thought to be a mediator of this corneal neovascularization (NV), therefore we would like to test the safety and efficacy of local VEGF blockade in the promotion of graft survival in high risk corneal transplants.
Detailed description
The purpose of this study is to test the effectiveness of a drug, bevacizumab (Avastin), in preventing blood vessels that often occur after a corneal transplantation which are considered at "high-risk" for rejection. In many cases these blood vessels lead to the graft rejection and eventual failure of the corneal transplant. It is hoped that this treatment will increase the chances of corneal graft survival.
The medication used in this study is called bevacizumab or Avastin (Genentech, Inc). It works by inhibiting the action of a molecule called vascular endothelial growth factor (VEGF). VEGF is a substance molecule that binds to certain cells to stimulate new blood vessel formation. When VEGF is bound to the drug, it cannot stimulate the formation and growth of new blood vessels. Growth of blood vessels into the cornea is a complication which can worsen the prognosis of your corneal transplant and put the transplant at a higher risk for rejection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Avastin® (bevacizumab) | Active comparator | Drug: Avastin® (bevacizumab)Treatment will begin on Day 0, immediately upon the conclusion of the penetrating keratoplasty procedure with an injection of 0.1 milliliter (mL) (2.5 mg) bevacizumab. Starting Day 1 post-transplant surgery, subjects will begin treatment with topical bevacizumab (1% solution). Topical treatment will be self-administered 4 times a day for 4 weeks. The study treatments are to be given in addition to standard of care treatments. Also, all patients will follow a standard post-operative follow-up visit schedule. |
| 0.9% NaCl & Refresh Liquigel | Placebo comparator | Drug: 0.9% NaCl & Refresh LiquigelTreatment will begin on Day 0, immediately upon the conclusion of the penetrating keratoplasty procedure with an injection of 0.1 mL 0.9% sodium chloride (NaCl). Starting Day 1 post-transplant surgery, subjects will begin treatment with topical Refresh Liquigel. Topical treatment will be self-administered 4 times a day for 4 weeks. The study treatments (both topical and subconjunctival injection) are to be given in addition to standard of care treatments. Also, all patients will follow a standard post-operative follow-up visit schedule. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age > 18 years
- Patient or legally authorized representative willing and able to provide written informed consent
- Willing and able to comply with study assessments for the full duration of the study
- High-risk characteristics for penetrating keratoplasty: Either presence of 1.) Corneal NV in one or more quadrants (≥ 3 clock hours NV ≥ 2mm from the limbus) OR 2.) Extension of corneal NV to graft-host junction in a previous failed graft
- In generally good stable overall health
Key exclusion criteria (14 listed)
- History of Stevens-Johnson syndrome or ocular pemphigoid
- Ocular or periocular malignancy
- Non-healing epithelial defect of at least 0.5x0.5 mm in host corneal bed lasting ≥6 weeks preoperatively
- Uncontrolled glaucoma
- Currently on dialysis
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 |
|---|---|---|
| Avastin® (bevacizumab)Also: Avastin, bevacizumabOne time subconjunctival injection of 0.1 mL (2.5 mg) bevacizumab followed by topical treatment with 1% solution bevacizumab four times a day for four weeks. | Drug | Avastin® (bevacizumab) |
| 0.9% NaCl & Refresh LiquigelAlso: Sodium Chloride, Refresh Liquigel, NaCLOne-time subconjunctival injection of 0.1mL 0.9% NaCl followed by topical treatment with Refresh Liquigel four times a day for four weeks | Drug | 0.9% NaCl & Refresh Liquigel |
Primary outcome
Number of Participants With Graft Failure at Week 39 and 52
Time frame: 12 months
Time from surgery to overall graft failure (regardless of cause). Graft failure was monitored throughout the entire study, but only the time points at which graft failure occurred are reported below.
1 secondary outcome
Endothelial Cell Density
Time frame: 52 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Reza Dana, MD, MPH, MSc principal investigator
Massachusetts Eye and Ear Infirmary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Avastin® (bevacizumab) and 0.9% NaCl & Refresh Liquigel in people with Corneal Neovascularization and Corneal Graft Failure, run by Reza Dana, MD 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 5 inclusion and 14 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: finished, as of the sponsor's last update on 15 Jun 2018. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Graft Failure at Week 39 and 52 (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Jun 2018.