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The purpose of this study is to determine the safety and efficacy of a drug [Pazopanib (Votrient)] as a treatment for corneal neovascularization. The cornea is the clear, central portion of the eye and neovascularization means blood vessel growth. The cornea is typically avascular, or without blood vessels. Corneal neovascularization in the cornea and can put vision at risk. Numerous diseases of the cornea such as inflammation, ischemia (restriction of blood supply), infection, degeneration (or deterioration), trauma, or corneal stem cell deficiency can lead to corneal neovascularization. This major ocular complication can lead to corneal scarring, edema (swelling), lipid deposits, and inflammation that may significantly alter your vision. In addition, it worsens the outcome of potential future treatments, such as a corneal transplant. A corneal transplant is a treatment that many patients with severe corneal disease may ultimately need.
Normally avascular, under many pathologic conditions, vessels may invade the cornea from the limbal vascular plexus. Infection, inflammation, ischemia, degeneration, or trauma, and the loss of the limbal stem cell barrier can cause corneal neovascularization. Growth of new vessels may result in corneal scarring, edema, lipid deposition, and inflammation that may alter visual acuity and is a leading cause of monocular visual impairment and blindness. Additionally, it results in the loss of immune response across the cornea, thereby worsening the prognosis of a subsequent penetrating keratoplasty (PK). Growth of new blood and lymphatic vessels from preexisting vessels are mediated by members of the vascular endothelial growth factor (VEGF) family. In previous studies, inhibition of new blood or lymphatic vessels has been achieved by neutralization of vascular endothelial growth factor A (VEGF-A). It has also been shown that platelet-derived growth factor-B (PDGF-B) plays a role in corneal and choroidal neovascularization by regulating mural cell recruitment. Inhibition of PDGF-B and VEGF-A signaling pathways has shown to more effectively promote vessel regression than solely inhibiting VEGF-A. Pazopanib is a drug designed to block these pathways, stop new growth, and regress old vessel growth.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pazopanib | Experimental | This is a single site, open label, safety and efficacy study of pazopanib (5mg/ml) where all 20 patients with corneal neovascularization in a single arm will receive pazopanib in one eye. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pazopanib (5mg/ml) | Drug | Topical pazopanib, 4 times per day for 3 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Heart Rate | Heart rate through was measured throughout the study to assess subjects for systemic adverse events. | 12 Weeks |
| Mean Arterial Pressure | Mean arterial pressure was measured throughout the study to assess subjects for systemic adverse events.. | 12 Weeks |
| Central Corneal Thickness | Pachymetry was used to measure the central corneal thickness of each study subject. Central corneal thickness was measured throughout the study to assess subjects for ocular adverse events. | 12 Weeks |
| Intaocular Pressure | Intaocular pressure is the measurement of pressure within the eye. Intaocular pressure was measured throughout the study to assess subjects for ocular adverse events. | 12 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Corneal Neovascular Area | Corneal neovascular area is the measurement of the area of the cornea where new blood vessels are forming. The mean Change in Corneal Neovascular Area from Baseline to 12 Week Time Point is reported below. | Through 12 weeks of Follow-Up |
| Corneal Invasion Area |
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Inclusion Criteria:
Exclusion Criteria:
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
History of any clotting disorder, including predisposition to hypercoagulation or any previous thromboembolic event
Major surgery within 1 month of screening
Has received treatment with anti-VEGF agents (topical, intraocular or systemic) within 60 days of study entry. This includes both approved and investigational treatments.
Has received investigational therapy within 60 days prior to study entry
Concurrent enrollment in another clinical investigational medicinal product or device study
Concurrent use of anti-VEGF agents
Corneal or ocular surface infection within 30 days prior to study entry
Full thickness or lamellar keratoplasty within 90 days prior to study entry
Other ocular surgeries within 60 days prior to study entry
Ocular or periocular malignancy
Soft Contact lens (excluding bandage contact lens) use within 2 weeks prior to study entry
Persistent epithelial defect (>1mm and ≥14 days duration) within 2 weeks prior to study entry
Intravitreal or periocular steroids within 4 weeks prior to study entry
Change in dose/frequency of topical steroids and/or nonsteroidal anti-inflammatory drugs (NSAIDs) within 2 weeks prior to study entry
Poorly controlled Hypertension: systolic blood pressure (BP) > 150 or diastolic BP > 90
Medical history of uncontrolled diabetes mellitus, with hemoglobin A1c (HbA1c) >7%
Women 45 years of age or younger that are of child bearing potential as defined by:
Subjects using hormone replacement therapy (HRT) that have experienced total cessation of menses for ≤ 1 year, OR, in questionable cases, have a follicle stimulating hormone (FSH) value <40 mIU/mL and an estradiol value > 40pg/mL (>140 pmol/L) OR have documented evidence OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT. Signs of current infection, including fever and current treatment with antibiotics
Participation in another simultaneous medical investigation or trial STUDY
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| Name | Affiliation | Role |
|---|---|---|
| Reza Dana, MD, MPH, MSc | Mass Eye and Ear Infirmary | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts Eye and Ear Infirmary | Boston | Massachusetts | 02114 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23233252 | Derived | Amparo F, Sadrai Z, Jin Y, Alfonso-Bartolozzi B, Wang H, Shikari H, Ciolino JB, Chodosh J, Jurkunas U, Schaumberg DA, Dana R. Safety and efficacy of the multitargeted receptor kinase inhibitor pazopanib in the treatment of corneal neovascularization. Invest Ophthalmol Vis Sci. 2013 Jan 17;54(1):537-44. doi: 10.1167/iovs.12-11032. |
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Patients were recruited and consented at the Massachusetts Eye and Ear Infirmary Cornea Department from November 2010 - October 2011.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pazopanib | This is a single site, open label, safety and efficacy study of pazopanib (5mg/ml) where all 20 patients with corneal neovascularization in a single arm will receive pazopanib in one eye. Frequency and Duration: 4 times per day for 3 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Pazopanib | This is a single site, open label, safety and efficacy study of pazopanib (5mg/ml) where all 20 patients with corneal neovascularization in a single arm will receive pazopanib in one eye. Frequency and Duration: 4 times per day for 3 weeks |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Heart Rate | Heart rate through was measured throughout the study to assess subjects for systemic adverse events. | All enrolled patients were analyzed. | Posted | Mean | Standard Deviation | Beats per Minutes | 12 Weeks |
|
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pazopanib | This is a single site, open label, safety and efficacy study of pazopanib (5mg/ml) where all 20 patients with corneal neovascularization in a single arm will receive pazopanib in one eye. Frequency and Duration: 4 times per day for 3 weeks |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tearing | Eye disorders | Non-systematic Assessment | Unilateral tearing secondary to punctal occlusion. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Reza Dana, MD, MPH, MSc | Massachusetts Eye and Ear Infirmary | 617-573-3313 | Cornea_Research@meei.harvard.edu |
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| ID | Term |
|---|---|
| D016510 | Corneal Neovascularization |
| D012393 | Rosacea |
| ID | Term |
|---|---|
| D003316 | Corneal Diseases |
| D005128 | Eye Diseases |
| D009389 | Neovascularization, Pathologic |
| D008679 | Metaplasia |
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| ID | Term |
|---|---|
| C516667 | pazopanib |
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Corneal Invasion area is the measurement of the fraction of the total corneal area that is invaded by blood vessels. The mean Change in Corneal invasion area from baseline to 12 Week Time Point is reported below. |
| 12 Weeks |
| Corneal Vessel Length | Corneal vessel length is the measurement of the length of the extent of vessels from end to end. The mean change in corneal vessel length from Baseline to 12 Week Time Point is reported below. | 12 Weeks |
| Corneal Vessel Caliber | Corneal vessel caliber is the measurement of the diameter of the corneal blood vessels. The mean change in the corneal vessel caliber from baseline to 12 week time point is reported below. | 12 Weeks |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Mean Arterial Pressure | Mean | Standard Deviation | mm Hg |
|
| Heart Rate | Mean | Standard Deviation | Beats per Minute |
|
| Intraocular Pressure | Mean | Standard Deviation | mm Hg |
|
| Central Corneal Thickness | Corneal pachymetry is used to measure central corneal thickness. This technique is used to gauge the functional status of the corneal endothelial cell layer. | Mean | Standard Deviation | microns |
|
|
|
| Primary | Mean Arterial Pressure | Mean arterial pressure was measured throughout the study to assess subjects for systemic adverse events.. | Posted | Mean | Standard Deviation | mmHG | 12 Weeks |
|
|
|
| Primary | Central Corneal Thickness | Pachymetry was used to measure the central corneal thickness of each study subject. Central corneal thickness was measured throughout the study to assess subjects for ocular adverse events. | All enrolled patients were analyzed. | Posted | Mean | Standard Deviation | Microns | 12 Weeks |
|
|
|
| Primary | Intaocular Pressure | Intaocular pressure is the measurement of pressure within the eye. Intaocular pressure was measured throughout the study to assess subjects for ocular adverse events. | Posted | Mean | Standard Deviation | mmHg | 12 Weeks |
|
|
|
| Secondary | Corneal Neovascular Area | Corneal neovascular area is the measurement of the area of the cornea where new blood vessels are forming. The mean Change in Corneal Neovascular Area from Baseline to 12 Week Time Point is reported below. | Mean Change in Corneal Neovascular Area (measuring the area of the corneal vessels) from Baseline to 12 Week Time Point. | Posted | Mean | Standard Deviation | millimeters squared | Through 12 weeks of Follow-Up |
|
|
|
| Secondary | Corneal Invasion Area | Corneal Invasion area is the measurement of the fraction of the total corneal area that is invaded by blood vessels. The mean Change in Corneal invasion area from baseline to 12 Week Time Point is reported below. | Posted | Mean | Standard Deviation | millimeters squared | 12 Weeks |
|
|
|
| Secondary | Corneal Vessel Length | Corneal vessel length is the measurement of the length of the extent of vessels from end to end. The mean change in corneal vessel length from Baseline to 12 Week Time Point is reported below. | Posted | Mean | Standard Deviation | millimeters | 12 Weeks |
|
|
|
| Secondary | Corneal Vessel Caliber | Corneal vessel caliber is the measurement of the diameter of the corneal blood vessels. The mean change in the corneal vessel caliber from baseline to 12 week time point is reported below. | Posted | Mean | Standard Deviation | millimeters | 12 Weeks |
|
|
|
| 0 |
| 20 |
| 12 |
| 20 |
|
| Stinging | Eye disorders | Non-systematic Assessment | Transitory stinging directly related to drug instillation. |
|
| Dryness | Eye disorders | Non-systematic Assessment |
|
| Blurred Vision | Eye disorders | Non-systematic Assessment | Blurred vision after drug instillation. |
|
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| D010335 |
| Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |