KDR2-2 Suspension Eyedrop in the Treatment of Neovascular Glaucoma (KDR-NVG) Trial

Study Overview
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Brief Summary
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The clinical trial is aimed to evaluate the anti-neovascular effect of KDR2-2 suspension eyedrop in the treatment of neovascular glaucoma. Fourty subjects would receive either 0.96 or 3.84 mg/per day/eye, in a QID fashion, ×7 days (those without complications can continue to 28 days). The anti-neovascular effect of KDR2-2 on iris neovascularization would be evaluated at day 1, day 7, day 14, day 28 after KDR2-2 usage.

Detailed Description
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Neovascular glaucoma (NVG) has a high blinding rate and poor prognosis. Anti-glaucoma surgery is the main stake of saving visual function and relieving pain, but the proliferation of iris neovascularization (NVI) makes it difficult to treat NVG. Normally, the patients need an intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents prior to glaucoma surgery to control the NVI proliferation. KDR2-2, a novel small-molecule tyrosine kinase inhibitor targeting VEGF receptor 2 (VEGFR2), has demonstrated anti-neovascular effect without obvious side-effects or complications in animal studies and a Phase I clinical trial (NCT04620109). In this study, 40 patients with NVG will be included to evaluate the effectiveness of KDR2-2 suspension eyedrop on NVI in NVG eyes. The included subjects would receive either 0.96 or 3.84 mg/day/eye, in a QID fashion, ×7 days (those without complications can continue to 28 days). This study aims to and propose a novel, non-invasive and more compliant method for the treatment of NVG.

Official Title
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Evaluation of Effectiveness of KDR2-2 Suspension Eyedrop on Neovascular Regression in the Treatment of Neovascular Glaucoma: an Exploratory Clinical Trial

Conditions
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Neovascular Glaucoma, Neovascularization

Intervention / Treatment
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* Drug: 4mg/ml KDR2-2 suspension eyedrop
* Drug: 16mg/ml KDR2-2 suspension eyedrop


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75; The best-corrected visual acuity (BCVA) of the included eyes was <0.01 (Snellen chart); The BCVA of the contralateral eye of the included subjects was >0.1; Patients with clinically diagnosed neovascular glaucoma; The diagnostic criteria for neovascularization glaucoma were as follows: Intraocular pressure > 21mmHg measured by Goldmann applanation tonometer; Neovascularization is seen in the iris or anterior chamber angle, with or without corneal edema; Compliance with follow up for more than 28 days and written informed consent obtained; Exclusion Criteria: Intravitreal injection of anti-VEGF drugs within 3 month before enrollment; Participation in other clinical trials within 1 month; Suffering from other ocular diseases that affect ocular examinations (e.g. keratopathy, uveitis, intraocular infection, etc.); Those who plan to receive ocular surgery during the follow-up period; Premenopausal women without birth control; Having other systemic diseases such as severe liver and kidney function damage, cardiovascular disorders, respiratory disorders, etc.) that may affect the anti-neovascular effect of KDR2-2 or more likely to develop adverse events ; Systemic infections under treatment; Any study in which the physician believes that the patient's condition will interfere with the clinical trial (e.g., the patient is prone to stress, mood disorders, depression, etc.);

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KDR2-2 group<br>The patients with NVG will receive 4.0 mg/ml or 16.0mg/ml KDR2-2 suspension eyedrop and the anti-neovascular effect of KDR2-2 would be evaluated during the follow-up visits. | Drug: 4mg/ml KDR2-2 suspension eyedrop<br>* KDR2-2 is a synthetic anti-angiogenic chemical compound with highly effective inhibition on vascular endothelial growth factor receptor-2 (VEGFR2), and an additional, moderate inhibitory effect on platelet-derived growth factor receptor β (PDGFRβ). KDR2-2 suspension eyedrop is developed for the treatment of iris neovascularization.<br>* Other names: Low-dose KDR2-2;Drug: 16mg/ml KDR2-2 suspension eyedrop<br>* KDR2-2 is a synthetic anti-angiogenic chemical compound with highly effective inhibition on vascular endothelial growth factor receptor-2 (VEGFR2), and an additional, moderate inhibitory effect on platelet-derived growth factor receptor β (PDGFRβ). KDR2-2 suspension eyedrop is developed for the treatment of iris neovascularization.<br>* Other names: High-dose KDR2-2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of iris neovascularization | Changes of the iris neovascularization using anterior photography or anterior optical coherence tomography angiography. | Day 0 and 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraocular pressure | Measurement of intraocular pressure using non-contact tonometer or iCare tonometer | Day 0，7 and 28 | 
| Best-corrected visual acuity | Measurement of best-corrected visual acuity with Snellen LogMAR Chart | Day 0，7 and 28 | 
| Adverse events | Adverse events related with the anti-angiogenic effect of KDR2-2 | Day 0，7 and 28 | 
| Changes of iris neovascularization | Changes of the iris neovascularization using anterior photography or anterior optical coherence tomography angiography. | Day 0，7 and 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neovascular Glaucoma, Neovascularization, anti-VEGF, vascular endothelial growth factor