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Treatment of Corneal Neovascularization With Topical Pazopanib

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier:
NCT01257750
First received: November 22, 2010
Last updated: October 5, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Corneal Neovascularization
Drug: Pazopanib (5mg/ml)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Topical Pazopanib in Treatment of Corneal Neovascularization

Resource links provided by NLM:


Further study details as provided by Massachusetts Eye and Ear Infirmary:

Primary Outcome Measures:
  • Ocular Adverse Events [ Time Frame: 12 Weeks of follow-up ] [ Designated as safety issue: Yes ]
    Incidence and severity of ocular adverse events, as identified by eye examination and visual acuity testing through week 12

  • Non-Ocular (Systemic) Adverse Events [ Time Frame: 12 Weeks ] [ Designated as safety issue: Yes ]
    Incidence and severity of other adverse events, as identified by physical examination, subject reporting, and changes in vital signs (blood pressure and heart rate) through week 12


Secondary Outcome Measures:
  • Corneal Neovascular Area [ Time Frame: Through 12 weeks of Follow-Up ] [ Designated as safety issue: No ]
    Changes in neovascular area: measuring the area of the corneal vessels.

  • Corneal Vessel Caliber [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Change in vessel caliber: measuring the mean diameter of the corneal vessels.

  • Corneal Invasion Area [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Change in invasion area: measuring the fraction of the total corneal area invaded by the vessels.

  • Corneal Vessel Length [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    Change in Vessel Length: defined as the mean measurement of the extent of vessels from end to end.


Enrollment: 20
Study Start Date: November 2010
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Pazopanib (5mg/ml)
Topical pazopanib, 4 times per day for 3 weeks
Other Name: Votrient

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01257750

Locations
United States, Massachusetts
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts Eye and Ear Infirmary
Investigators
Principal Investigator: Reza Dana, MD, MPH, MSc Mass Eye and Ear Infirmary
  More Information

No publications provided by Massachusetts Eye and Ear Infirmary

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier: NCT01257750     History of Changes
Other Study ID Numbers: 10-09-063
Study First Received: November 22, 2010
Results First Received: October 5, 2012
Last Updated: October 5, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts Eye and Ear Infirmary:
corneal neovascularization
pazopanib
votrient
rosacea

Additional relevant MeSH terms:
Corneal Neovascularization
Neovascularization, Pathologic
Corneal Diseases
Eye Diseases
Metaplasia
Pathologic Processes

ClinicalTrials.gov processed this record on November 27, 2014