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).
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector
Cincinnati Eye Institute
Cincinnati, Ohio, 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
Adverse Events
Incidence and severity of ocular and non-ocular adverse events (AEs) for each cohort
Time frame: From Day 0 (pre-treatment) through Week 24
Ocular and Non -Ocular Adverse Events after week 24
Incidence and severity of ocular and non-ocular AEs from Day 0 (pre-treatment) through Weeks 52 and Week 260 for each cohort
Time frame: From Day 0 (pre-treatment) and through Weeks 52, 104, 156, 208 and 260
Systemic Immunogenic Response
Change in concentration of Anti-NG101 Transgene protein (aflibercept) antibodies, Anti-AAV8 Neutralizing antibodies, and Anti-AAV8 Antibodies in serum samples
Time frame: From Day -14 to Weeks 4, 8, 12, 24, 52, and 104
Systemic Immunogenic Response
Change in concentration of expressed aflibercept protein in serum samples
Time frame: From Day -14 to Weeks 4, 12, and 104
Systemic Immunogenic Response
Change in AAV vector (NG101) genome copies as measured by qPCR (quantitative polymerase chain reaction) in blood samples
Time frame: From Day -14 to Day 7, and Weeks 2, 4, and week 12.
Systemic Immunogenic Response
Change in concentration of expressed aflibercept protein in vitreous samples
Time frame: From Day 0 (pre-treatment) to Weeks 24, 52, and 104
Signs of CNV (choroidal neovascularization) Activity
Change of 1 or more signs of CNV activity assessed by OCT (Optical coherence tomography)
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Time frame: From Day -7 to Weeks 8, 24, 52, and 104
Central Subfield Thickness (CST)
Change in CST assessed with OCT
Time frame: From Day -7 to Weeks 24, 52, 104, 156, 208, and 260
Best Corrected Visual Acuity (BCVA)
Change in BCVA assessed with Early Treatment Diabetic Retinopathy Study (ETDRS) scale
Time frame: From Day -7 to Weeks 24, 52, 104, 156, 208 and 260
Cumulative Number of Rescue Therapy Injections
The cumulative number of rescue therapy injections per subject to maintain CNV control in the Study Eye
Time frame: Through Weeks 24, 52, 104, 156, 208, and 260