Clinical trial NCT05984927: NG101 AAV Gene Therapy in Subjects With Wet Age-Related Macular Degeneration
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Age-Related Macular Degeneration
Keywords: Wet macular degeneration
Neovascular Age-Related Macular Degeneration
Macular Degeneration
Choroidal Neovascularization
Retinal Degeneration
Eye Diseases
Retinal Diseases
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Gene Therapy
Anti-vascular endothelial growth factor therapy
Anti-VEGF therapy
Lead sponsor: Neuracle Genetics, Inc
Sponsor class: INDUSTRY
Collaborators: name: ORA, Inc.
First posted: 2023-08-09
Enrollment: 18
Sex: ALL
Minimum age (years): 50
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose Escalation Study with 3 dose cohorts
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Adverse Events
timeFrame: From Day 0 (pre-treatment) through Week 24
Secondary outcomes:
measure: Ocular and Non -Ocular Adverse Events after week 24
timeFrame: From Day 0 (pre-treatment) and through Weeks 52, 104, 156, 208 and 260
measure: Systemic Immunogenic Response
timeFrame: From Day -14 to Weeks 4, 8, 12, 24, 52, and 104
measure: Systemic Immunogenic Response
timeFrame: From Day -14 to Weeks 4, 12, and 104
measure: Systemic Immunogenic Response
timeFrame: From Day -14 to Day 7, and Weeks 2, 4, and week 12.
measure: Systemic Immunogenic Response
timeFrame: From Day 0 (pre-treatment) to Weeks 24, 52, and 104
measure: Signs of CNV (choroidal neovascularization) Activity
timeFrame: From Day -7 to Weeks 8, 24, 52, and 104
measure: Central Subfield Thickness (CST)
timeFrame: From Day -7 to Weeks 24, 52, 104, 156, 208, and 260
measure: Best Corrected Visual Acuity (BCVA)
timeFrame: From Day -7 to Weeks 24, 52, 104, 156, 208 and 260
measure: Cumulative Number of Rescue Therapy Injections
timeFrame: Through Weeks 24, 52, 104, 156, 208, and 260
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Eye Institute
state: Ohio
city: Vancouver
country: Canada
facility: Vancouver Coastal Health Research Institute
state: British Columbia
city: Toronto
country: Canada
facility: Sunnybrook Ophthalmology and Vision Services
state: Ontario
city: Toronto
country: Canada
facility: Vitreous Retina Macula Specialists of Toronto
state: Ontario
Study officials:
affiliation: Neuracle Genetics, Inc. Medical Director
name: Christopher D Riemann, MD
role: PRINCIPAL_INVESTIGATOR
References: