VEGFA-targeting Gene Therapy to Treat Retinal and Choroidal Neovascularization Diseases

A Safety and Efficacy Study of VEGFA-targeting Gene Therapy to Treat Refractory Retinal and Choroidal Neovascularization Diseases

Patients who respond to anti-VEGF therapy but with refractory retinal and choroidal neovascularization diseases including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion-Macular edema (RVO-ME).

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetic Macular Edema; Retinal Vein Occlusion; Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Genetic: BD311

Detailed Description

Choroidal and retinal angiogenesis diseases are a group of diseases characterized by choroidal or retinal angiogenesis. These diseases are often correlated with the macular area, which may lead to significant visual loss. In this study, The IDLV vector is engineered to carry the VEGFA antibody gene. The gene is delivered to the RPE cells to express the VEGFA antibody which neutralizes the VEGFA activity in the posterior segment of the eye of individuals who have progressed to various forms of neovascular macular degeneration.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Eye & ENT Hospital of Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with nAMD at the age ≥50; Or patients with diabetic macular edema (DME) at the age ≥18; Or patients with macular edema following retinal vein occlusion (RVO-ME) at the age ≥18.
2. Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity ≤63 and letter score ≥19 Corresponding Snellen vision ≤20/63 and ≥20/400).
3. OCT confirms the presence of intraretinal fluid or subretinal fluid in the fovea.
4. Have received anti-VEGF therapy in the past and have responded to anti-VEGF therapy.
5. With refractory conditions: repeated anti-VEGF treatments are required due to the disease condition. When the treatment is interrupted, the disease condition recurs (OCT examination indicates increased subretinal/inner effusion in the macula)
6. For patients with both eyes suffered, enroll the one with more severe condition.
7. Routine blood test, liver and kidney function, coagulation index of patients is normal：AST/ALT < 2.5 × ULN; TB < 1.5 × ULN; PT < 1.5 × ULN; Hb > 10 g/dL (male) and > 9 g/dL (female); PLT > 100 × 10^3/µL; eGFR > 30 mL/min/1.73 m^2.

Subjects voluntarily join the study, sign an informed consent form, have good compliance, and cooperate with follow-up.

Exclusion Criteria:

1. Choroidal neovascularization or macular edema induced by other diseases.
2. Any other factors that affect vision improvement in the study eye, such as fibrosis, atrophy, or RPE tear in the fovea of the macula.
3. The study eye already has severe proliferative retinopathy, such as retinal neovascularization, traction retinal detachment, etc. (only for DME and RVO-ME patients) .
4. Retinal detachment or advanced glaucoma in the study eye.
5. Implants in the study eye (except intraocular lenses).
6. Received internal eye surgery within 3 months prior to enrollment.
7. Vitrectomy surgery on the study eye.
8. Received intravitreal glucocorticoid or other clinical research drugs (except anti-VEGF therapy) within 6 months prior to enrollment.
9. Myocardial infarction, cerebrovascular accident or transient ischemic attack occurred within 6 months prior to enrollment.
10. Poorly controlled hypertension under maximum medication (systolic blood pressure>180 mmHg, diastolic blood pressure>100 mmHg).
11. Poor blood glucose control under medication (fasting blood glucose is greater than or equal to 10.0 umol/L).
12. Women who are willing to give birth; pregnant/breastfeeding women Have received gene therapy in the past.

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: BD311 Adults single group; Administered by suprachoroidal injection. Dosage form: injection solution. Dose: 500uL. Frequency of administration: one time injection.	Genetic: BD311; Integration-deficient lentiviral vector (IDLV) expressing VEGFA antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-related adverse events	Observe and record incidences of AE and SAE related to VEGFA-targeting gene therapy drug BD311 (IDLV expressing VEGFA antibody) administration.	At multiple timepoints after infusion up to 12 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in macular intraretinal fluid (IRF)	The presence of macular intraretinal fluid (IRF) will be determined by optical coherence tomography (OCT).	At multiple timepoints after infusion up to 12 months.
Changes in subretinal fluid (SRF)	The presence of subretinal fluid (SRF) will be determined by optical coherence tomography (OCT).	At multiple timepoints after infusion up to 12 months.
Change in central retinal thickness (CRT)	Central retinal thickness will be measured by Optical Coherence Tomography (OCT).	At multiple timepoints after infusion up to 12 months.
Changes in the area of choroidal neovascularization	Using Fluorescein angiography (FFA) and indocyanine green angiography (ICGA) to assess the areas of choroidal neovascularization. Only for patients with nAMD.	At multiple timepoints after infusion up to 12 months.
Changes in the area of fluorescein leakage	Using Fluorescein angiography (FFA) and indocyanine green angiography (ICGA) to assess the areas of fluorescein leakage. Only for patients with nAMD.	At multiple timepoints after infusion up to 12 months.
The number of rescue treatments	Rescue treatments that require vitreous anti-VEGF injections due to illness.	At multiple timepoints after infusion up to 12 months.
Evaluate the visual improvement	Subjects will be examined for best corrected visual acuity (BCVA).	At multiple timepoints after infusion up to 12 months.

Collaborators and Investigators

• Sponsor: Shanghai BDgene Co., Ltd.
• Collaborators: Eye & ENT Hospital of Fudan University
• Investigators: Study Director: Gezhi Xu, Dr, Eye & ENT Hospital of Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2021
• Primary Completion (Actual): November 30, 2024
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: September 18, 2021
• First Submitted That Met QC Criteria: October 28, 2021
• First Posted (Actual): October 29, 2021

Study Record Updates

• Last Update Posted (Actual): May 18, 2025
• Last Update Submitted That Met QC Criteria: May 14, 2025
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Diabetic macular edema; neovascular age-related macular degeneration; Retinal diseases; Neovascularization; DME; nAMD; Choroidal diseases; RVO-ME; Retinal vein occlusion-Macular edema
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Eye Diseases; Embolism and Thrombosis; Uveal Diseases; Retinal Diseases; Retinal Degeneration; Choroid Diseases; Metaplasia; Venous Thrombosis; Thrombosis; Macular Degeneration; Choroidal Neovascularization; Neovascularization, Pathologic; Macular Edema; Wet Macular Degeneration; Retinal Vein Occlusion
• Other Study ID Numbers: BD311

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