Back to resultsThe Safety and Efficacy of KDR2-2 Suspension Eye Drops in the Treatment of Corneal Neovascularization
Primary Purpose
Corneal Neovascularization
Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
KDR2-2 suspension eye drops
Sponsored by
About this trial
This is an interventional treatment trial for Corneal Neovascularization
Eligibility Criteria
Inclusion Criteria:
- voluntarily participate in the trial, sign the informed consent form, and follow up according to the time specified by the trial;
- 18~75 years old, without gender limit;
- Superficial or deep corneal progressive neovascularization induced by trauma, chemical burns, corneal transplantation and inflammation: the growth of corneal new vessels≥ 2 mm from the limbus within 1 week to 2 months.
Exclusion Criteria:
- Obvious corneal epithelial defects (>1mm), or a history of persistent corneal epithelial defects in the past 3 months (>1mm, ≥14 days);
- Anti-VEGF drugs have been injected locally in the target eye within 3 months, or anti-VEGF drugs have been used systemically within 2 months;
- Recent eye surgery (except for keratoplasty) within 3 months, or planned eye surgery during the trial period;
- Systemic use of glucocorticoid drugs, or intraocular or periocular injection of glucocorticoid drugs within 1 month;
- Contact lenses use within the past 2 weeks (except bandage lenses);
- Stable corneal neovascularization: > 6 months;
- History of coagulation abnormalities (such as end-stage liver disease), or current anticoagulant drugs other than aspirin (such as warfarin, heparin, enoxaparin or similar anticoagulants);
- Uncontrolled clinical problems (such as tumors, HIV infection, hepatitis C virus infection, active hepatitis B or other serious chronic infections, serious mental, neurological, cardiovascular, urinary, respiratory and other system diseases, etc.); Uncontrolled hypertension: systolic blood pressure ≥150mmHg or diastolic blood pressure ≥90mmHg; uncontrolled diabetes: A1C>7%;
- Unwillingness/inability to take effective contraceptive measures during the trial period;
- Female subjects have a positive blood pregnancy test;
- Participated in a drug clinical trial within 3 months;
- The investigator believes that it is not suitable for inclusion.
Sites / Locations
- Zhongshan Opthalmic CenterRecruiting
- Zhongshan Ophthalmic Center, Sun Yat-Sen UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
No Intervention
Experimental
Experimental
Experimental
Arm Label
Control group
Low-concentration group
Medium-concentration group
High-concentration group
Arm Description
Patients in the control group received 0.1% fluorometholone eye drops (0.1% fluorometholone + 0.05% tacrolimus eye drops for patients after corneal transplantation). The patients applied 0.1% fluorometholone eye drops 4 times daily for 10 weeks. Patients were instructed to continue with their usual ophthalmic medication regimens, such as topical antibacterial and antiviral drugs.
Patients in the low-concentration group applied 4mg/ml KDR2-2 suspension eye drops 4 times daily for 6 weeks. The rest of the medication regimen is the same as the control group.
Patients in the medium-concentration group applied 4mg/ml KDR2-2 suspension eye drops 4 times daily for 6 weeks. The rest of the medication regimen is the same as the control group.
Patients in the High-concentration group applied 4mg/ml KDR2-2 suspension eye drops 4 times daily for 6 weeks. The rest of the medication regimen is the same as the control group.
Outcomes
Primary Outcome Measures
the changes of the size and extent of corneal neovascularization
The efficacy of KDR2-2 eye drops treatment on corneal neovascularization was evaluated by comparing corneal anterior segment photographs acquired at baseline with photographs acquired on the follow-up visits. Size and extent of CNV was investigated by four primary metrics: (1) neovascular area ratio, the ration of the area of the neovascularization to the area of the cornea, (2) vessel length (VL), the total length of the vessels projected into the cornea, (3) vessel caliber, the mean diameter of the corneal vessels, and (4) Corneal neovascularization progression/stabilization/regression rate
Secondary Outcome Measures
the changes of visual acuity
The uncorrected visual acuity and best corrected visual acuity were assessed through ETDRs chart at baseline and all the follow-up visits. The alterations in visual acuity were evaluated in all patients.
the changes of intraocular pressure
The intraocular pressure of the patients was assessed by iCARE at baseline and all the follow-up visits. The alterations of intraocular pressure were evaluated.
the changes of central corneal thickness
The central corneal thickness was assessed by anterior segment OCT at baseline and all the follow-up visits. The alterations in central corneal thickness were evaluated.
the changes of conjunctival hyperemia score
The conjunctival hyperemia score was assessed by severity from 0 (no signs of conjunctival hyperemia) to 3 (serious conjunctival hyperemia) by the clinician at baseline and all the follow-up visits.The changes of conjunctival hyperemia score were evaluated.
the changes of corneal fluorescein staining score
The corneal fluorescein staining score was assessed by NEI grading system by the clinician at baseline and all the follow-up visits.The NEI grading system divides the cornea into 5 zones: central, superior, temporal, nasal, and inferior. For each zone, the amount of corneal fluorescein staining is graded on a scale of 0 to 3: 0=normal or negative slit-lamp findings; 1=milder superfacial stippling; 2=moderate or punctate staining, including superfacial abrasion of the cornea; and 3=severe abrasion or corneal erosion, deep corneal abrasion, or recurrent erosion. The alterations in corneal fluorescein staining score were evaluated.
the changes of corneal sensation
The corneal sensation was assessed through Cochet-Bonnet aesthesiometer by the clinician at baseline and 4 weeks after drug withdrawal. The corneal sensation was assessed at five points on the cornea, including the central, superior, temporal, nasal, and inferior points.
the morphological changes of corneal subepithelial nerve
In vivo confocal laser scanning microscopy was performed by the clinician at baseline and 4 weeks after drug withdrawal. The density and length of the corneal subepithelial nerve were analysed.
the changes of ocular tolerability score
Ocular tolerability score (including ocular tolerability, burning sensation, pain, itching and blurred vision) was assessed by severity from 0 (absent) to 3 (severe) by questionnaire.
Full Information
NCT ID
NCT05011916
First Posted
August 7, 2021
Last Updated
August 17, 2021
Sponsor
Zhongshan Ophthalmic Center, Sun Yat-sen University
1. Study Identification
Unique Protocol Identification Number
NCT05011916
Brief Title
The Safety and Efficacy of KDR2-2 Suspension Eye Drops in the Treatment of Corneal Neovascularization
Official Title
An Exploratory Clinical Study on the Safety and Efficacy of KDR2-2 Suspension Eye Drops in the Treatment of Corneal Neovascularization
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Unknown status
Study Start Date
August 10, 2021 (Actual)
Primary Completion Date
August 9, 2022 (Anticipated)
Study Completion Date
August 9, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zhongshan Ophthalmic Center, Sun Yat-sen University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
KDR2-2, as a tyrosine kinase inhibitor, has a strong inhibitory effect on VEGFR2 and a moderate inhibitory effect on PDGFR-β. It can be used for the treatment of corneal neovascularization. The main purpose of this study is to explore the efficacy and safety of KDR2-2 suspension eye drops in the treatment of corneal neovascularization. This study is a single-center, prospective, randomized controlled clinical study. A total of 60 patients with corneal neovascularization were enrolled in this study, and they were randomly divided into 4 groups, including the control group, the KDR2-2 low-concentration (4mg/ml) group, the medium-concentration (10mg/ml) group, and the high-concentration (20mg/ml) group, with 15 subjects in each group. The control group applied 0.1% fluorometholone eye drops, and the test groups applied KDR2-2 suspension eye drops with 0.1% fluorometholone eye drops. Patients applied KDR2-2 eye drops four times daily for 6 weeks and were followed up to 10 weeks. The follow-up time points were baseline, 1 week, 2 weeks, 4 weeks, 6 weeks after medication, and 4 weeks after drug withdrawal. Relevant ophthalmological examinations (including visual acuity, intraocular pressure, slit lamp microscopy, central corneal thickness measurement, corneal fluorescein staining assessment, corneal sensitivity measurement, corneal confocal microscope examination, and anterior segment and fundus photography) are performed at each time. And the ocular tolerability score and adverse events of each patient were recorded. By comparative analysis, the efficacy and safety of KDR2-2 eye drops in the treatment of corneal neovascularization were evaluated.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corneal Neovascularization
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
4
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control group
Arm Type
No Intervention
Arm Description
Patients in the control group received 0.1% fluorometholone eye drops (0.1% fluorometholone + 0.05% tacrolimus eye drops for patients after corneal transplantation). The patients applied 0.1% fluorometholone eye drops 4 times daily for 10 weeks. Patients were instructed to continue with their usual ophthalmic medication regimens, such as topical antibacterial and antiviral drugs.
Arm Title
Low-concentration group
Arm Type
Experimental
Arm Description
Patients in the low-concentration group applied 4mg/ml KDR2-2 suspension eye drops 4 times daily for 6 weeks. The rest of the medication regimen is the same as the control group.
Arm Title
Medium-concentration group
Arm Type
Experimental
Arm Description
Patients in the medium-concentration group applied 4mg/ml KDR2-2 suspension eye drops 4 times daily for 6 weeks. The rest of the medication regimen is the same as the control group.
Arm Title
High-concentration group
Arm Type
Experimental
Arm Description
Patients in the High-concentration group applied 4mg/ml KDR2-2 suspension eye drops 4 times daily for 6 weeks. The rest of the medication regimen is the same as the control group.
Intervention Type
Drug
Intervention Name(s)
KDR2-2 suspension eye drops
Intervention Description
All patients were instructed to instill one drop four times per day in the study eye for 6 weeks.
Primary Outcome Measure Information:
Title
the changes of the size and extent of corneal neovascularization
Description
The efficacy of KDR2-2 eye drops treatment on corneal neovascularization was evaluated by comparing corneal anterior segment photographs acquired at baseline with photographs acquired on the follow-up visits. Size and extent of CNV was investigated by four primary metrics: (1) neovascular area ratio, the ration of the area of the neovascularization to the area of the cornea, (2) vessel length (VL), the total length of the vessels projected into the cornea, (3) vessel caliber, the mean diameter of the corneal vessels, and (4) Corneal neovascularization progression/stabilization/regression rate
Time Frame
Baseline, 1 week, 2 weeks, 4 weeks and 6 weeks after medication, and 4 weeks after drug withdrawal
Secondary Outcome Measure Information:
Title
the changes of visual acuity
Description
The uncorrected visual acuity and best corrected visual acuity were assessed through ETDRs chart at baseline and all the follow-up visits. The alterations in visual acuity were evaluated in all patients.
Time Frame
Baseline, 1 week, 2 weeks, 4 weeks and 6 weeks after medication, and 4 weeks after drug withdrawal
Title
the changes of intraocular pressure
Description
The intraocular pressure of the patients was assessed by iCARE at baseline and all the follow-up visits. The alterations of intraocular pressure were evaluated.
Time Frame
Baseline, 1 week, 2 weeks, 4 weeks and 6 weeks after medication, and 4 weeks after drug withdrawal
Title
the changes of central corneal thickness
Description
The central corneal thickness was assessed by anterior segment OCT at baseline and all the follow-up visits. The alterations in central corneal thickness were evaluated.
Time Frame
Baseline, 1 week, 2 weeks, 4 weeks and 6 weeks after medication, and 4 weeks after drug withdrawal
Title
the changes of conjunctival hyperemia score
Description
The conjunctival hyperemia score was assessed by severity from 0 (no signs of conjunctival hyperemia) to 3 (serious conjunctival hyperemia) by the clinician at baseline and all the follow-up visits.The changes of conjunctival hyperemia score were evaluated.
Time Frame
Baseline, 1 week, 2 weeks, 4 weeks and 6 weeks after medication, and 4 weeks after drug withdrawal
Title
the changes of corneal fluorescein staining score
Description
The corneal fluorescein staining score was assessed by NEI grading system by the clinician at baseline and all the follow-up visits.The NEI grading system divides the cornea into 5 zones: central, superior, temporal, nasal, and inferior. For each zone, the amount of corneal fluorescein staining is graded on a scale of 0 to 3: 0=normal or negative slit-lamp findings; 1=milder superfacial stippling; 2=moderate or punctate staining, including superfacial abrasion of the cornea; and 3=severe abrasion or corneal erosion, deep corneal abrasion, or recurrent erosion. The alterations in corneal fluorescein staining score were evaluated.
Time Frame
Baseline, 1 week, 2 weeks, 4 weeks and 6 weeks after medication, and 4 weeks after drug withdrawal
Title
the changes of corneal sensation
Description
The corneal sensation was assessed through Cochet-Bonnet aesthesiometer by the clinician at baseline and 4 weeks after drug withdrawal. The corneal sensation was assessed at five points on the cornea, including the central, superior, temporal, nasal, and inferior points.
Time Frame
Baseline and 4 weeks after drug withdrawal
Title
the morphological changes of corneal subepithelial nerve
Description
In vivo confocal laser scanning microscopy was performed by the clinician at baseline and 4 weeks after drug withdrawal. The density and length of the corneal subepithelial nerve were analysed.
Time Frame
Baseline and 4 weeks after drug withdrawal
Title
the changes of ocular tolerability score
Description
Ocular tolerability score (including ocular tolerability, burning sensation, pain, itching and blurred vision) was assessed by severity from 0 (absent) to 3 (severe) by questionnaire.
Time Frame
1 week, 2 weeks, 4 weeks and 6 weeks after medication
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
voluntarily participate in the trial, sign the informed consent form, and follow up according to the time specified by the trial;
18~75 years old, without gender limit;
Superficial or deep corneal progressive neovascularization induced by trauma, chemical burns, corneal transplantation and inflammation: the growth of corneal new vessels≥ 2 mm from the limbus within 1 week to 2 months.
Exclusion Criteria:
Obvious corneal epithelial defects (>1mm), or a history of persistent corneal epithelial defects in the past 3 months (>1mm, ≥14 days);
Anti-VEGF drugs have been injected locally in the target eye within 3 months, or anti-VEGF drugs have been used systemically within 2 months;
Recent eye surgery (except for keratoplasty) within 3 months, or planned eye surgery during the trial period;
Systemic use of glucocorticoid drugs, or intraocular or periocular injection of glucocorticoid drugs within 1 month;
Contact lenses use within the past 2 weeks (except bandage lenses);
Stable corneal neovascularization: > 6 months;
History of coagulation abnormalities (such as end-stage liver disease), or current anticoagulant drugs other than aspirin (such as warfarin, heparin, enoxaparin or similar anticoagulants);
Uncontrolled clinical problems (such as tumors, HIV infection, hepatitis C virus infection, active hepatitis B or other serious chronic infections, serious mental, neurological, cardiovascular, urinary, respiratory and other system diseases, etc.); Uncontrolled hypertension: systolic blood pressure ≥150mmHg or diastolic blood pressure ≥90mmHg; uncontrolled diabetes: A1C>7%;
Unwillingness/inability to take effective contraceptive measures during the trial period;
Female subjects have a positive blood pregnancy test;
Participated in a drug clinical trial within 3 months;
The investigator believes that it is not suitable for inclusion.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qian Wang, PhD
Phone
18843014719
Email
419059130@qq.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jin Yuan, PhD
Phone
13825141659
Email
yuanjincornea@163.com
Facility Information:
Facility Name
Zhongshan Opthalmic Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuan Jin, Professor
Phone
8602087333391
Email
yuanjincornea@126.com
Facility Name
Zhongshan Ophthalmic Center, Sun Yat-Sen University
City
Guangzhou
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qian Wang, MD
Phone
86-018843014719
Email
419059130@qq.com
First Name & Middle Initial & Last Name & Degree
Jin Yuan, PHD
12. IPD Sharing Statement
Learn more about this trial
The Safety and Efficacy of KDR2-2 Suspension Eye Drops in the Treatment of Corneal Neovascularization
We'll reach out to this number within 24 hrs