NG101 AAV Gene Therapy in Subjects With 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 will evaluate the safety, tolerability, and preliminary efficacy of NG101 AAV gene therapy administered by subretinal injections into a single selected eye as a single selected dose for patients with wet age-related macular degeneration (wAMD).

Study Overview

• Status: Active, not recruiting
• Conditions: Age-Related Macular Degeneration
• Intervention / Treatment: Genetic: NG101 AAV gene therapy

Detailed Description

This is a Phase 1/2a, multicenter, open-label, dose escalation study to evaluate the safety, tolerability, and preliminary efficacy of NG101 AAV gene therapy, administered by subretinal injection in patients with active wAMD symptoms. The study will be conducted at approximately 5 sites in Canada and the USA.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 3N9
      • Vancouver Coastal Health Research Institute
  • Ontario
    • Toronto, Ontario, Canada, M8X 2X3
      • Vitreous Retina Macula Specialists of Toronto
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Ophthalmology and Vision Services
• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Cincinnati Eye Institute
  • Texas
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NG101 Gene Therapy Group 1; Single subretinal injection of 1x10^9 vector genomes of NG101 AAV gene therapy	Genetic: NG101 AAV gene therapy; Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector; Other Names: NG101
Experimental: NG101 Gene Therapy Group 2; Single subretinal injection of 3x10^9 vector genomes of NG101 AAV gene therapy	Genetic: NG101 AAV gene therapy; Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector; Other Names: NG101
Experimental: NG101 Gene Therapy Group 3; Single subretinal injection of 8x10^9 vector genomes of NG101 AAV gene therapy	Genetic: NG101 AAV gene therapy; Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector; Other Names: NG101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Incidence and severity of ocular and non-ocular adverse events (AEs) for each cohort	From Day 0 (pre-treatment) through Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ocular and Non -Ocular Adverse Events after week 24	Incidence and severity of ocular and non-ocular AEs from Day 0 (pre-treatment) through Weeks 52 and Week 260 for each cohort	From Day 0 (pre-treatment) and through Weeks 52, 104, 156, 208 and 260
Systemic Immunogenic Response	Change in concentration of expressed aflibercept protein in serum samples	From Day -14 to Weeks 4, 12, and 104
Central Subfield Thickness (CST)	Change in CST assessed with OCT	From Day -7 to Weeks 24, 52, 104, 156, 208, and 260
Best Corrected Visual Acuity (BCVA)	Change in BCVA assessed with Early Treatment Diabetic Retinopathy Study (ETDRS) scale	From Day -7 to Weeks 24, 52, 104, 156, 208 and 260
Systemic Immunogenic Response	Change in concentration of Anti-NG101 Transgene protein (aflibercept) antibodies, Anti-AAV8 Neutralizing antibodies, and Anti-AAV8 Antibodies in serum samples	From Day -14 to Weeks 4, 8, 12, 24, 52, and 104
Systemic Immunogenic Response	Change in AAV vector (NG101) genome copies as measured by qPCR (quantitative polymerase chain reaction) in blood samples	From Day -14 to Day 7, and Weeks 2, 4, and week 12.
Systemic Immunogenic Response	Change in concentration of expressed aflibercept protein in vitreous samples	From Day 0 (pre-treatment) to Weeks 24, 52, and 104
Signs of CNV (choroidal neovascularization) Activity	Change of 1 or more signs of CNV activity assessed by OCT (Optical coherence tomography)	From Day -7 to Weeks 8, 24, 52, and 104
Cumulative Number of Rescue Therapy Injections	The cumulative number of rescue therapy injections per subject to maintain CNV control in the Study Eye	Through Weeks 24, 52, 104, 156, 208, and 260

Collaborators and Investigators

• Sponsor: Elisigen, Inc.
• Collaborators: ORA, Inc.
• Investigators: Principal Investigator: Christopher D Riemann, MD, Neuracle Genetics, Inc. Medical Director

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2023
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: July 24, 2023
• First Submitted That Met QC Criteria: August 2, 2023
• First Posted (Actual): August 9, 2023

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Gene Therapy; Eye Diseases; Antineoplastic Agents; Retinal Diseases; Macular Degeneration; Choroidal Neovascularization; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Anti-VEGF therapy; Retinal Degeneration; Neovascular Age-Related Macular Degeneration; Growth Substances; Growth Inhibitors; Wet macular degeneration; Anti-vascular endothelial growth factor therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases, Hereditary; Uveal Diseases; Choroid Diseases; Metaplasia; Neovascularization, Pathologic; Pathological Conditions, Signs and Symptoms; Retinal Diseases; Eye Diseases; Retinal Degeneration; Macular Degeneration; Choroidal Neovascularization; Wet Macular Degeneration
• Other Study ID Numbers: NG101WA-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes