NG101 AAV Gene Therapy in Subjects with Wet Age-Related Macular Degeneration
Phase 1
Recruiting
- Conditions
- Age-Related Macular Degeneration
- Interventions
- Genetic: NG101 AAV gene therapy
- Registration Number
- NCT05984927
- Lead Sponsor
- Neuracle Genetics, Inc
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 18
Inclusion Criteria
- Subjects ≥ 50 and ≤ 89 years of age with a diagnosis of active subfoveal CNV secondary to wAMD in the Study Eye
- BCVA between 20/40 and 20/400 in the Study Eye, with BCVA decrement primarily attributable to wAMD
- 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).
- Must be pseudo phakic (status post cataract surgery) in the Study Eye
- 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.
- 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)
- 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
- Willingness and ability to comply with schedule for follow-up visits and postoperative evaluations
Exclusion Criteria
- CNV or macular edema in the Study Eye secondary to any causes other than AMD
- 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
- Any ophthalmic condition that precludes adequate ophthalmic examination or requires treatment
- Retinal detachment or history of retinal detachment in the Study Eye
- 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
- 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
- History of vitrectomy, trabeculectomy, glaucoma tube-shunt procedure, minimally invasive glaucoma surgery (MIGS) device, or other filtration surgery in the Study Eye
- Photodynamic therapy or retinal laser for the treatment of wAMD within the last 6 months
- 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
- Any previous intraocular or refractive surgery on the Study Eye within 6 months
- Any previous gene therapy in the Study Eye
- Presence of an ocular implant in the Study Eye at Screening, excluding intraocular lens and custom flex iris prosthesis
- 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
- Medically uncontrolled diabetes, defined as HbA1C > 8.0
- History of ocular melanoma
- History of any known inherited retinal disease
- 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
- 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
- Active hepatitis B or C
- History of human immunodeficiency virus (HIV), active tuberculosis, and/or syphilis
- Any significant illness that would preclude study compliance and follow-up
- Subjects who, in the Investigator's opinion, lack the mental capacity to provide written informed consent for study participation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description NG101 Gene Therapy Group 2 NG101 AAV gene therapy Single subretinal injection of 3x10\^9 vector genomes of NG101 AAV gene therapy NG101 Gene Therapy Group 1 NG101 AAV gene therapy Single subretinal injection of 1x10\^9 vector genomes of NG101 AAV gene therapy NG101 Gene Therapy Group 3 NG101 AAV gene therapy Single subretinal injection of 8x10\^9 vector genomes of NG101 AAV gene therapy
- Primary Outcome Measures
Name Time Method Adverse Events From Day 0 (pre-treatment) through Week 24 Incidence and severity of ocular and non-ocular adverse events (AEs) for each cohort
- Secondary Outcome Measures
Name Time Method Ocular and Non -Ocular Adverse Events after week 24 From Day 0 (pre-treatment) and through Weeks 52, 104, 156, 208 and 260 Incidence and severity of ocular and non-ocular AEs from Day 0 (pre-treatment) through Weeks 52 and Week 260 for each cohort
Systemic Immunogenic Response From Day 0 (pre-treatment) to Weeks 24, 52, and 104 Change in concentration of expressed aflibercept protein in vitreous samples
Signs of CNV (choroidal neovascularization) Activity From Day -7 to Weeks 8, 24, 52, and 104 Change of 1 or more signs of CNV activity assessed by OCT (Optical coherence tomography)
Central Subfield Thickness (CST) From Day -7 to Weeks 24, 52, 104, 156, 208, and 260 Change in CST assessed with OCT
Best Corrected Visual Acuity (BCVA) From Day -7 to Weeks 24, 52, 104, 156, 208 and 260 Change in BCVA assessed with Early Treatment Diabetic Retinopathy Study (ETDRS) scale
Cumulative Number of Rescue Therapy Injections Through Weeks 24, 52, 104, 156, 208, and 260 The cumulative number of rescue therapy injections per subject to maintain CNV control in the Study Eye
Trial Locations
- Locations (4)
Sunnybrook Ophthalmology and Vision Services
🇨🇦Toronto, Ontario, Canada
Cincinnati Eye Institute
🇺🇸Cincinnati, Ohio, United States
Vancouver Coastal Health Research Institute
🇨🇦Vancouver, British Columbia, Canada
Vitreous Retina Macula Specialists of Toronto
🇨🇦Toronto, Ontario, Canada