Topical IL-1-Ra for Treatment of Corneal Neovascularization

The purpose of this study is to determine the effectiveness and safety of Interleukin-1-Receptor Antagonist eye drops for the treatment of corneal blood vessels.

Study Overview

• Status: Terminated
• Conditions: Corneal Neovascularization
• Intervention / Treatment: Drug: Placebo; Drug: IL-1Ra

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. This study is designed to investigate whether Interleukin-1-Receptor Antagonist is a drug that is both safe and effective in blocking VEGF pathways, stopping new growth, and reducing old vessel growth.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts Eye and Ear Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ability to provide written informed consent and comply with study assessments for the full duration of the study
• Age > 18 years
• Patients with superficial or deep corneal NV that extends farther than 1 mm from the limbus
• Patients are in generally good stable overall healthExclusion Criteria: • Has received treatment with anti-VEGF agents (topical, intraocular or systemic) within 30 days of study entry
• Corneal or ocular surface infection within 30 days prior to study entry• Ocular or periocular malignancy
• 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 2 weeks prior to study entry
• Change in dose/frequency of topical steroids and/or NSAIDs within 2 weeks prior to study entry
• Pregnancy (positive pregnancy test) or lactation
• Premenopausal women not using contraception
• Signs of current infection, including fever and current treatment with antibiotics
• Participation in another simultaneous medical investigation or trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Placebo first, then IL-1RA; It is our intent that 10 patients will complete a course of treatment with placebo, followed by a course of treatment with 5% custom made topical IL-1Ra.	Drug: Placebo; Custom eye drop eye three times a day in both eyes for a period of 6 weeks; Drug: IL-1Ra; 5% custom made topical IL-1Ra 3 times a day in both eyes for a period of 6 weeks; Other Names: Kineret
EXPERIMENTAL: IL-1RA first, then Placebo; It is our intent that 10 patients will complete a course of treatment with 5% custom made topical IL-1Ra, followed by a course of treatment with placebo	Drug: Placebo; Custom eye drop eye three times a day in both eyes for a period of 6 weeks; Drug: IL-1Ra; 5% custom made topical IL-1Ra 3 times a day in both eyes for a period of 6 weeks; Other Names: Kineret

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Ocular Adverse Event	Incidence and severity of ocular adverse events, as identified by eye examination and visual acuity testing.	64 Weeks
Extent of Neovascular Area (NA)	The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis.	64 weeks
Vessel Caliber (VC), Measuring the Mean Diameter of the Corneal Vessels	The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis.	64 Weeks
Invasion Area (IA), Measuring the Fraction of the Total Corneal Area Invaded by the Vessels	The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis.	64 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Spectacle-Corrected Visual Acuity (BSCVA)	The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis.	64 weeks
Central Corneal Thickness	The Principal Investigator decided to terminate the study and stop enrollment because of difficulty recruiting subjects. Although data were collected for this Outcome Measure, no analysis was performed. All records were destroyed following the required retention period. Data are no longer available for analysis.	64 Weeks

Collaborators and Investigators

• Sponsor: Reza Dana, MD

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (ACTUAL): March 1, 2011
• Study Completion (ACTUAL): March 1, 2011

Study Registration Dates

• First Submitted: June 4, 2009
• First Submitted That Met QC Criteria: June 4, 2009
• First Posted (ESTIMATE): June 8, 2009

Study Record Updates

• Last Update Posted (ACTUAL): May 8, 2017
• Last Update Submitted That Met QC Criteria: May 5, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Corneal Diseases; Metaplasia; Neovascularization, Pathologic; Corneal Neovascularization; Antirheumatic Agents; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: 09-03-017; Protocol #09-03-017 (OTHER: Massachusetts Eye and Ear Infirmary)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES