NG101 AAV Gene Therapy in Subjects With Wet Age-Related Macular Degeneration
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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 6 sites in Canada and the USA.
Study Design
Arms and Interventions
| 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:
|
| 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:
|
| 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:
|
Outcome Measures
Primary Outcome Measures
- Adverse Events [Day 0 (pre-treatment) and Week 24]
Incidence and severity of ocular and non-ocular adverse events (AEs) for each cohort
Secondary Outcome Measures
- Ocular and Non -Ocular Adverse Events after week 24 [Day 0 (pre-treatment) and from Week 24 to Week 260]
Incidence and severity of ocular and non-ocular AEs after Week 24 to Week 260 for each cohort
- Systemic Immunogenic Response [Day 0, Week 12, 24, 52, and 104]
Change in concentration of expressed aflibercept protein in vitreous samples
- Systemic Immunogenic Response [Day -7 Weeks 4, 12, and 104]
Change in concentration of expressed aflibercept protein in serum samples
- Systemic Immunogenic Response [Day -7, Week 4, and week 12]
Change in AAV vector (NG101) genome copies as measured by PCR in blood samples
- Systemic Immunogenic Response [Day -7, Week 4, week 8, week 12, week 24, week 52, and week 104]
Change in concentration of Anti-NG101 Transgene protein antibodies, Anti-AAV8 Neutralizing antibodies, and Anti-AAV8 Antibodies in serum samples
- Signs of CNV Activity [At every visit from Screening through Week 104]
Change of 1 or more signs of CNV activity assessed by Optical coherence tomography
- Central Retinal Thickness (CRT) [from Screening to Weeks 260]
Change in CRT assessed with OCT
- Best Corrected Visual Acuity (BCVA) [from Screening to Weeks 260]
Change in BCVA assessed with Early Treatment Diabetic Retinopathy Study (ETDRS) scale
- Cumulative Number of Rescue Therapy Injections [From Week 24 to Week 260]
The cumulative number of rescue therapy injections per subject to maintain CNV control
Eligibility Criteria
Criteria
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 20/63 and 20/400 in the Study Eye, with BCVA decrement primarily attributable to wAMD
-
Administration of at least 3 anti-VEGF injections in the past 6 months, the most recent of which was within 2 months prior to Screening.
-
Must be pseudo phakic (status post cataract surgery) in the Study Eye
-
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:
-
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 in the center of the macula
-
Any ophthalmic condition that precludes adequate ophthalmic examination or requires ancillary testing
-
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
-
Any prior treatment with photodynamic therapy or retinal laser for the treatment of wAMD
-
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
-
Any 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 severe cardiovascular, cerebrovascular, and neurodegenerative diseases, including active malignancy and immunocompromised conditions.
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Vitreous Retina Macula Specialists of Toronto | Toronto | Ontario | Canada | M8X 2X3 |
Sponsors and Collaborators
- Neuracle Genetics, Inc
- ORA, Inc.
Investigators
- Principal Investigator: Christopher D Riemann, MD, Neuracle Genetics, Inc. Medical Director
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NG101WA-01