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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Neovascular Glaucoma; Neovascularization
• Intervention / Treatment: Drug: 4mg/ml KDR2-2 suspension eyedrop; Drug: 16mg/ml KDR2-2 suspension eyedrop

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 51000
      • Zhongshan Ophthalmic Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: KDR2-2 group; 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; 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.; Other Names: Low-dose KDR2-2; Drug: 16mg/ml KDR2-2 suspension eyedrop; 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.; Other Names: High-dose KDR2-2

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Xiulan Zhang, MD, PhD, Zhongshan Ophthalmic Center, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: April 13, 2021
• First Submitted That Met QC Criteria: April 13, 2021
• First Posted (Actual): April 14, 2021

Study Record Updates

• Last Update Posted (Estimated): December 11, 2024
• Last Update Submitted That Met QC Criteria: December 6, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: anti-VEGF; Neovascularization; vascular endothelial growth factor; Neovascular Glaucoma
• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Metaplasia; Ocular Hypertension; Neovascularization, Pathologic; Glaucoma; Glaucoma, Neovascular; Pharmaceutical Solutions; Ophthalmic Solutions
• Other Study ID Numbers: 2021KYPJ080

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No