Treatment of Corneal Neovascularization With Topical Pazopanib

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.

Inclusion Criteria:

- Ability to provide written informed consent

- Ability to comply with study assessments and study requirements (for example, able to
open the eye drop foil-wrap packaging and eye drop vials, willing to adhere to the
daily dosing schedule) for the full duration of study

- Age > 18 years

- Patients with superficial or deep corneal neovascularization that extends farther than
1 mm from the limbus

- Patients are in stable overall health

- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase
and bilirubin ≤ 1.5x upper limit of normal (ULN) or isolated bilirubin >1.5x ULN is
acceptable if bilirubin is fractionated and direct bilirubin <35%

- Single QTcF < 450 msec; or QTcF < 480 msec in subjects with Bundle Branch Block

- A female is eligible to enter and participate in this study if she is of
Non-childbearing potential (i.e., physiologically incapable of becoming pregnant),

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:

- No history of a hysterectomy

- No history of a bilateral oophorectomy (ovariectomy)

- No history of a bilateral tubal ligation

- Not post-menopausal

- 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