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Treatment of Corneal Neovascularization With Topical Pazopanib

Primary Purpose

Corneal Neovascularization

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Pazopanib (5mg/ml)

About this trial

This is an interventional treatment trial for Corneal Neovascularization focused on measuring corneal neovascularization, pazopanib, votrient, rosacea

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Massachusetts Eye and Ear Infirmary

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pazopanib

Arm Description

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.

Outcomes

Primary Outcome Measures

Heart Rate

Heart rate through was measured throughout the study to assess subjects for systemic adverse events.

Mean Arterial Pressure

Mean arterial pressure was measured throughout the study to assess subjects for systemic adverse events..

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.

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.

Secondary Outcome Measures

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.

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.

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.

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.

Full Information

NCT ID

NCT01257750

First Posted

November 22, 2010

Last Updated

December 19, 2017

Sponsor

Reza Dana, MD

1. Study Identification

Unique Protocol Identification Number

NCT01257750

Brief Title

Treatment of Corneal Neovascularization With Topical Pazopanib

Official Title

Safety and Efficacy of Topical Pazopanib in Treatment of Corneal Neovascularization

Study Type

Interventional

2. Study Status

Record Verification Date

December 2017

Overall Recruitment Status

Completed

Study Start Date

November 2010 (undefined)

Primary Completion Date

January 2012 (Actual)

Study Completion Date

January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Reza Dana, MD

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Corneal Neovascularization

Keywords

corneal neovascularization, pazopanib, votrient, rosacea

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Pazopanib

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Pazopanib (5mg/ml)

Other Intervention Name(s)

Votrient

Intervention Description

Topical pazopanib, 4 times per day for 3 weeks

Primary Outcome Measure Information:

Title

Heart Rate

Description

Heart rate through was measured throughout the study to assess subjects for systemic adverse events.

Time Frame

12 Weeks

Title

Mean Arterial Pressure

Description

Mean arterial pressure was measured throughout the study to assess subjects for systemic adverse events..

Time Frame

12 Weeks

Title

Central Corneal Thickness

Description

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.

Time Frame

12 Weeks

Title

Intaocular Pressure

Description

Intaocular pressure is the measurement of pressure within the eye. Intaocular pressure was measured throughout the study to assess subjects for ocular adverse events.

Time Frame

12 Weeks

Secondary Outcome Measure Information:

Title

Corneal Neovascular Area

Description

Time Frame

Through 12 weeks of Follow-Up

Title

Corneal Invasion Area

Description

Time Frame

12 Weeks

Title

Corneal Vessel Length

Description

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.

Time Frame

12 Weeks

Title

Corneal Vessel Caliber

Description

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.

Time Frame

12 Weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Reza Dana, MD, MPH, MSc

Organizational Affiliation

Mass Eye and Ear Infirmary

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts Eye and Ear Infirmary

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

23233252

Citation

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.

Results Reference

derived

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Treatment of Corneal Neovascularization With Topical Pazopanib

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