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

NCT ID: NCT05099094

Last Updated: 2025-05-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-25
• Study Completion Date: 2025-09-30

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).

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.

Conditions

Neovascular Age-related Macular Degeneration; Diabetic Macular Edema; Retinal Vein Occlusion

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BD311 Adults single group

Administered by suprachoroidal injection. Dosage form: injection solution. Dose: 500uL. Frequency of administration: one time injection.

Group Type: EXPERIMENTAL

BD311

Intervention Type: GENETIC

Integration-deficient lentiviral vector (IDLV) expressing VEGFA antibody

Interventions

BD311

Integration-deficient lentiviral vector (IDLV) expressing VEGFA antibody

Intervention Type: GENETIC

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eye & ENT Hospital of Fudan University

OTHER

Sponsor Role: collaborator

Shanghai BDgene Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gezhi Xu, Dr

Role: STUDY_DIRECTOR

Eye & ENT Hospital of Fudan University

Locations

Eye & ENT Hospital of Fudan University

Shanghai, SH, China

Countries

China

References

Romano F, Lamanna F, Gabrielle PH, Teo KYC, Battaglia Parodi M, Iacono P, Fraser-Bell S, Cornish EE, Nassisi M, Viola F, Agarwal A, Samanta A, Chhablani J, Staurenghi G, Invernizzi A. Update on Retinal Vein Occlusion. Asia Pac J Ophthalmol (Phila). 2023 Mar-Apr 01;12(2):196-210. doi: 10.1097/APO.0000000000000598. Epub 2023 Feb 14.

Reference Type: DERIVED

PMID: 36912792 (View on PubMed)

Other Identifiers

BD311

Identifier Type: -

Identifier Source: org_study_id