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

Sponsor

Shanghai BDgene Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05099094

Collaborator

Eye & ENT Hospital of Fudan University (Other)

Enrollment

Location

Arm

21.2

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Neovascular Age-related Macular Degeneration Diabetic Macular Edema Retinal Vein Occlusion	Genetic: BD311	Early Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 25, 2021

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity ≤63 and letter score ≥19 Corresponding Snellen vision ≤20/63 and ≥20/400).
OCT confirms the presence of intraretinal fluid or subretinal fluid in the fovea.
Have received anti-VEGF therapy in the past and have responded to anti-VEGF therapy.
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)
For patients with both eyes suffered, enroll the one with more severe condition.
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:

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