Age-Related Macular Degeneration
Conditions
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
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.
Interventions
GENETICNG101 AAV gene therapy
Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector
Sponsors
Elisigen, Inc.
ORA, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose Escalation Study with 3 dose cohorts
Eligibility
Sex/Gender
ALL
Age
50 Years to 89 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 -14 to Weeks 4, 8, 12, 24, 52, and 104 | Change in concentration of Anti-NG101 Transgene protein (aflibercept) antibodies, Anti-AAV8 Neutralizing antibodies, and Anti-AAV8 Antibodies in serum 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 |
Countries
Canada, United States
Contacts
PRINCIPAL_INVESTIGATORChristopher D Riemann, MD
Neuracle Genetics, Inc. Medical Director
Outcome results
None listed