NG101 AAV Gene Therapy in Subjects With Wet Age-Related Macular Degeneration

NCT ID: NCT05984927

Last Updated: 2026-01-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-08
• Study Completion Date: 2030-01-31

Brief Summary

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).

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.

Conditions

Age-Related Macular Degeneration

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NG101 Gene Therapy Group 1

Single subretinal injection of 1x10\^9 vector genomes of NG101 AAV gene therapy

Group Type: EXPERIMENTAL

NG101 AAV gene therapy

Intervention Type: GENETIC

Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector

NG101 Gene Therapy Group 2

Single subretinal injection of 3x10\^9 vector genomes of NG101 AAV gene therapy

Group Type: EXPERIMENTAL

NG101 AAV gene therapy

Intervention Type: GENETIC

Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector

NG101 Gene Therapy Group 3

Single subretinal injection of 8x10\^9 vector genomes of NG101 AAV gene therapy

Group Type: EXPERIMENTAL

NG101 AAV gene therapy

Intervention Type: GENETIC

Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector

Interventions

NG101 AAV gene therapy

Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector

Intervention Type: GENETIC

Other Intervention Names

NG101

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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ORA, Inc.

INDUSTRY

Sponsor Role: collaborator

Elisigen, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher D Riemann, MD

Role: PRINCIPAL_INVESTIGATOR

Neuracle Genetics, Inc. Medical Director

Locations

Cincinnati Eye Institute

Cincinnati, Ohio, United States

Retina Consultants of Texas

Bellaire, Texas, United States

Vancouver Coastal Health Research Institute

Vancouver, British Columbia, Canada

Sunnybrook Ophthalmology and Vision Services

Toronto, Ontario, Canada

Vitreous Retina Macula Specialists of Toronto

Toronto, Ontario, Canada

Countries

United States; Canada

Other Identifiers

NG101WA-01

Identifier Type: -

Identifier Source: org_study_id