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

Diabetic Macular Edema Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05099094
• Other study ID #: BD311
• Status: Recruiting
• Phase: Early Phase 1
• Start date: November 25, 2021
• Est. completion date: September 2023

Study information

• Verified date: August 2022
• Source: Shanghai BDgene Co., Ltd.
• Contact: Yujia Cai, PhD
• Phone: 17721291876
• Email: yujia.cai[@]bdgene.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: September 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Choroidal Neovascularization
• Diabetic Macular Edema
• Macular Degeneration
• Macular Edema
• Neovascular Age-related Macular Degeneration
• Neovascularization, Pathologic
• Retinal Vein Occlusion
• Wet Macular Degeneration

Intervention

Genetic:
• BD311
Integration-deficient lentiviral vector (IDLV) expressing VEGFA antibody

Locations

Country	Name	City	State
China	Eye & ENT Hospital of Fudan University	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai BDgene Co., Ltd.	Eye & ENT Hospital of Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	Evaluate the visual improvement	Subjects will be examined for best corrected visual acuity (BCVA).	At multiple timepoints after infusion up to 12 months.