Gene therapy for wet age-related macular degeneration

A Phase 1/2a Open-label Study to Evaluate Safety, Tolerability and Preliminary Efficacy of NG101 AAV Gene Therapy in Subjects With Wet Age-Related Macular Degeneration

This study is testing a new gene therapy for people with wet age-related macular degeneration to see if it can safely improve their vision symptoms.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 50 Years to 89 Years
• Sex: All
• Sponsor: Neuracle Genetics, Inc (Industry-sponsored)
• Drugs / interventions: radiation
• Locations: 4 sites (Cincinnati, Ohio and 3 other locations)
• Trial ID: NCT05984927 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, tolerability, and preliminary efficacy of NG101 AAV gene therapy administered via subretinal injections in patients with wet age-related macular degeneration (wAMD). It is a Phase 1/2a, multicenter, open-label, dose escalation study involving approximately 5 sites across Canada and the USA. Participants will receive a single selected dose of the therapy in one eye, with the aim of assessing its effects on active symptoms of wAMD.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 50 to 89 with active subfoveal choroidal neovascularization due to wAMD who have previously received anti-VEGF injections.

Not a fit: Patients with stable or inactive wAMD or those who do not meet the age and treatment history criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option that may improve vision and quality of life for patients suffering from wet age-related macular degeneration.

How similar studies have performed: Other studies have shown promise with gene therapy approaches for retinal diseases, indicating potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

1. Subjects ≥ 50 and ≤ 89 years of age with a diagnosis of active subfoveal CNV secondary to wAMD in the Study Eye
2. BCVA between 20/40 and 20/400 in the Study Eye, with BCVA decrement primarily attributable to wAMD
3. Administration of at least 3 anti-VEGF (vascular endothelial growth factor) injections in the study eye in the past 6 months for clinically active wAMD, the most recent of which was within 1 month prior to Screening Day -14 (Visit 1).
4. Must be pseudo phakic (status post cataract surgery) in the Study Eye
5. Female and Male reproductive status: Female subjects must be either: (1) of non-childbearing potential; or (2) of childbearing potential and using an acceptable method of birth control with a negative pregnancy test. Male subjects agree to refrain from sperm donations and practice contraception to avoid any pregnancy for 3 months after administration of NG101.
6. Normal blood pressure (BP) and heart rate (HR), or near normal BP and HR not considered clinically significant (NCS) by the Investigator at the Screening Day -14 (Visit 1) and Day -7 (Visit 2)
7. Willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to the performance of any study-related procedures
8. Willingness and ability to comply with schedule for follow-up visits and postoperative evaluations

Exclusion Criteria:

1. CNV or macular edema in the Study Eye secondary to any causes other than AMD
2. Any condition preventing visual acuity improvement in the Study Eye, e.g., fibrosis, atrophy, or retinal pigment epithelial tear involving the center of the macula
3. Any ophthalmic condition that precludes adequate ophthalmic examination or requires treatment
4. Retinal detachment or history of retinal detachment in the Study Eye
5. Active uncontrolled glaucoma with intraocular pressure (IOP) ≥ 30 mmHg despite treatment with more than 2 glaucoma medications, advanced glaucoma with cup-to-disc ratio of ≥ 0.9, visual field defects secondary to glaucoma that involve the macula, and/or optic atrophy from glaucoma
6. History of intravitreal therapy in the Study Eye, such as intravitreal steroid injection or an investigational product, other than anti-VEGF therapy, in the 6 months prior to Screening
7. History of vitrectomy, trabeculectomy, glaucoma tube-shunt procedure, minimally invasive glaucoma surgery (MIGS) device, or other filtration surgery in the Study Eye
8. Photodynamic therapy or retinal laser for the treatment of wAMD within the last 6 months
9. Any prior therapeutic radiation in the region of the Study Eye such as whole brain radiation, proton beam radiation, gamma knife treatment, or plaque brachytherapy
10. Any previous intraocular or refractive surgery on the Study Eye within 6 months
11. Any previous gene therapy in the Study Eye
12. Presence of an ocular implant in the Study Eye at Screening, excluding intraocular lens and custom flex iris prosthesis
13. Any diabetic retinopathy or other retinal vascular disease including retinal vein occlusion, retinal artery occlusion, retinal arterial macro aneurysm, ocular ischemic syndrome, retinal vasculitis, vitritis, posterior uveitis
14. Medically uncontrolled diabetes, defined as HbA1C \> 8.0
15. History of ocular melanoma
16. History of any known inherited retinal disease
17. Currently taking any anticoagulant therapy, which is deemed medically necessary and cannot be permanently stopped at least 2 weeks prior to NG101 injection, excluding prophylactic low-dose aspirin therapy
18. Any underlying systemic diseases as unstable or severe cardiovascular, cerebrovascular, dementia or neurodegenerative diseases of a level that prevents adequate evaluation of the subject during the study, active malignancy or currently undergoing treatment for active malignancy at Screening or a history of malignancy that precludes completion of this 260 week study, and immunocompromised conditions and/or need for immunosuppressive therapy
19. Active hepatitis B or C
20. History of human immunodeficiency virus (HIV), active tuberculosis, and/or syphilis
21. Any significant illness that would preclude study compliance and follow-up
22. Subjects who, in the Investigator's opinion, lack the mental capacity to provide written informed consent for study participation

Where this trial is running

Cincinnati, Ohio and 3 other locations

• Cincinnati Eye Institute — Cincinnati, Ohio, United States (Recruiting)
• Vancouver Coastal Health Research Institute — Vancouver, British Columbia, Canada (Recruiting)
• Sunnybrook Ophthalmology and Vision Services — Toronto, Ontario, Canada (Recruiting)
• Vitreous Retina Macula Specialists of Toronto — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Principal investigator: Christopher D Riemann, MD — Neuracle Genetics, Inc. Medical Director
• Study coordinator: Sheila Yi

Conditions Age-Related Macular Degeneration; Wet macular degeneration; Neovascular Age-Related Macular Degeneration; Macular Degeneration; Choroidal Neovascularization; Retinal Degeneration; Eye Diseases; Retinal Diseases