Corneal NeovascularizationPhase 1/2NCT01257750
Treatment of Corneal Neovascularization With Topical Pazopanib
A Phase 1/2 study testing Pazopanib (5mg/ml) in people with Corneal Neovascularization, run by Reza Dana, MD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Corneal Neovascularization
- What is being tested?
- Pazopanib (5mg/ml)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2010to Jan 2012
- 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
- 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),
Who cannot join
- 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
Show all 24Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, 02114
About this study
Official title: Safety and Efficacy of Topical Pazopanib in Treatment of Corneal Neovascularization
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.
Read the 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.
- Conditions
- Corneal Neovascularization
- Being tested
- Pazopanib (5mg/ml)
- Keywords
- corneal neovascularization, pazopanib, votrient, rosacea
- Medical subject headings
- Corneal Neovascularization, Rosacea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pazopanib (5mg/ml)Drug
Also called Votrient
Topical pazopanib, 4 times per day for 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Pazopanib (5mg/ml) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart Rate
Heart rate through was measured throughout the study to assess subjects for systemic adverse events.
Measured: 12 Weeks
Mean Arterial Pressure
Mean arterial pressure was measured throughout the study to assess subjects for systemic adverse events..
Measured: 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.
Measured: 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.
Measured: 12 Weeks
Secondary outcomes (4)
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.
Measured: Through 12 weeks of Follow-Up
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.
Measured: 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.
Measured: 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.
Measured: 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2010 (estimated)
- Study startNov 2010
- Primary completionJan 2012
- Study completionJan 2012
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.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 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, Mass Eye and Ear Infirmary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01257750
- Sponsor's protocol ID
- 10-09-063
- Status last verified
- Dec 2017
- First submitted
- 22 Nov 2010
- Last updated
- 18 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 23233252
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Topical Pazopanib in Treatment of Corneal Neovascularization
- ClinicalTrials.gov ID
- NCT01257750
- Acronym / sponsor ID
- 10-09-063
- Conditions
- Corneal Neovascularization
- Keywords
- corneal neovascularization, pazopanib, votrient, rosacea
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Reza Dana, MDUniversity, hospital or other
- Study start
- Nov 2010
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 10 Dec 2010 (estimated)
- Results
- Posted 6 Nov 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pazopanib | Experimental | Drug: Pazopanib (5mg/ml)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (24 listed)
- 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
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 |
|---|---|---|
| Pazopanib (5mg/ml)Also: VotrientTopical pazopanib, 4 times per day for 3 weeks | Drug | Pazopanib |
Primary outcome
Heart Rate
Time frame: 12 Weeks
Heart rate through was measured throughout the study to assess subjects for systemic adverse events.
Mean Arterial Pressure
Time frame: 12 Weeks
Mean arterial pressure was measured throughout the study to assess subjects for systemic adverse events..
Central Corneal Thickness
Time frame: 12 Weeks
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
Time frame: 12 Weeks
Intaocular pressure is the measurement of pressure within the eye. Intaocular pressure was measured throughout the study to assess subjects for ocular adverse events.
4 secondary outcomes
Corneal Neovascular Area
Time frame: Through 12 weeks of Follow-Up
Corneal Invasion Area
Time frame: 12 Weeks
Corneal Vessel Length
Time frame: 12 Weeks
Corneal Vessel Caliber
Time frame: 12 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23233252Amparo 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.
Related trials for Corneal Neovascularization
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Fine-needle Diathermy Combined With Subconjunctival Bevacizumab for Corneal Neovascularization
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Clinical Study of Intrastromal Anti-VEGF Injection for Corneal Neovascularization.
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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
Mass 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 Pazopanib (5mg/ml) in people with Corneal Neovascularization, 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 8 inclusion and 24 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 18 Jan 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. 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 6 Nov 2012). 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?
Heart Rate (time frame: 12 Weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01257750, which also lists 1 linked publication.
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 18 Jan 2018.