The Safety and Efficacy of KDR2-2 Suspension Eye Drops in the Treatment of Corneal Neovascularization

Phase 1

• Conditions: Corneal Neovascularization
• Interventions: Drug: KDR2-2 suspension eye drops

• Registration Number: NCT05011916
• Lead Sponsor: Zhongshan Ophthalmic Center, Sun Yat-sen University

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2021-08
• Study First Submitted: 2021-08-07
• Study Start: 2021-08-10
• Study First Submitted QC: 2021-08-17
• Last Update Submitted: 2021-08-17
• Study First Posted: 2021-08-18
• Last Update Posted: 2021-08-18
• Primary Completion: 2022-08-09
• Study Completion: 2022-08-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. voluntarily participate in the trial, sign the informed consent form, and follow up according to the time specified by the trial;
2. 18~75 years old, without gender limit;
3. 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

1. Obvious corneal epithelial defects (>1mm), or a history of persistent corneal epithelial defects in the past 3 months (>1mm, ≥14 days);
2. 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;
3. Recent eye surgery (except for keratoplasty) within 3 months, or planned eye surgery during the trial period;
4. Systemic use of glucocorticoid drugs, or intraocular or periocular injection of glucocorticoid drugs within 1 month;
5. Contact lenses use within the past 2 weeks (except bandage lenses);
6. Stable corneal neovascularization: > 6 months;
7. 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);
8. 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%;
9. Unwillingness/inability to take effective contraceptive measures during the trial period;
10. Female subjects have a positive blood pregnancy test;
11. Participated in a drug clinical trial within 3 months;
12. The investigator believes that it is not suitable for inclusion.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low-concentration group	KDR2-2 suspension eye drops	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.
Medium-concentration group	KDR2-2 suspension eye drops	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.
High-concentration group	KDR2-2 suspension eye drops	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.

Primary Outcome Measures

Name	Time	Method
the changes of the size and extent of corneal neovascularization	Baseline, 1 week, 2 weeks, 4 weeks and 6 weeks after medication, and 4 weeks after drug withdrawal	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

Name	Time	Method
the changes of central corneal thickness	Baseline, 1 week, 2 weeks, 4 weeks and 6 weeks after medication, and 4 weeks after drug withdrawal	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	Baseline, 1 week, 2 weeks, 4 weeks and 6 weeks after medication, and 4 weeks after drug withdrawal	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	Baseline, 1 week, 2 weeks, 4 weeks and 6 weeks after medication, and 4 weeks after drug withdrawal	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 morphological changes of corneal subepithelial nerve	Baseline and 4 weeks after drug withdrawal	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	1 week, 2 weeks, 4 weeks and 6 weeks after medication	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.
the changes of visual acuity	Baseline, 1 week, 2 weeks, 4 weeks and 6 weeks after medication, and 4 weeks after drug withdrawal	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	Baseline, 1 week, 2 weeks, 4 weeks and 6 weeks after medication, and 4 weeks after drug withdrawal	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 corneal sensation	Baseline and 4 weeks after drug withdrawal	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.

Trial Locations

Locations (2)

Zhongshan Ophthalmic Center, Sun Yat-Sen University; 🇨🇳 Guangzhou, China

Zhongshan Opthalmic Center; 🇨🇳 Guangzhou, Guangdong, China