Neovascular Age-related Macular Degeneration, Wet Age-related Macular Degeneration
Conditions
Keywords
Choroidal Neovascularizatio, ADVM-022, CNV, ADVM-022-01, AAV.7m8, Anti-VEGF therapy, Blindness, Gene therapy, Aflibercept (Eylea), Age-Related Macular Degeneration, Wet Macular Degeneration, Retinal Degeneration, Retinal Diseases, Eye Diseases, AAV Vector, Adverum, wAMD, AMD, wet AMD
Brief summary
ADVM-022 (AAV.7m8-aflibercept) is a gene therapy product developed for the treatment of neovascular (wet) age-related macular degeneration (wet AMD). Wet AMD is a serious condition and the leading cause of blindness in the elderly. The available therapies for treating wet AMD require life-long intravitreal (IVT) injections every 4-12 weeks to maintain efficacy. A one-time IVT administration of ADVM-022 has the potential to treat wet AMD by providing durable expression of therapeutic levels of intraocular anti-VEGF protein (aflibercept) and maintaining the vision of patients. ADVM-022 is designed to reduce the current treatment burden which often results in undertreatment and vision loss in patients with wet AMD receiving anti-VEGF therapy in clinical practice.
Detailed description
This open-label, multicenter, dose-ranging study will evaluate 2 dose levels in up to 30 subjects (15 per dose) with active choroidal neovascularization (CNV) secondary to AMD. Subjects who are under active anti-VEGF treatment and have demonstrated a meaningful response to anti-VEGF therapy will be considered for participation in this study. The primary endpoint for this study is safety and tolerability of ADVM-022. All subjects will continue to be assessed for 104 weeks following treatment with ADVM-022.
Interventions
BIOLOGICALADVM-022
ADVM-022 (AAV.7m8-aflibercept) is a recombinant, replication-deficient adeno-associated virus (AAV.7m8) gene therapy vector carrying a coding sequence for aflibercept
Sponsors
Adverum Biotechnologies, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label, dose-ranging clinical study to evaluate the safety and tolerability of ADVM-022 in subjects with wet AMD.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 50 * Diagnosis of neovascular (wet) AMD * BCVA ETDRS Snellen equivalent between ≤20/32 and ≥20/320 for each cohort * Subjects must be under active anti-VEGF treatment for wAMD and received a minimum of 2 injections within 4 months prior to screening * Demonstrated a meaningful response to anti-VEGF therapy * Willing and able to provide consent
Exclusion criteria
* History of retinal disease in the study eye other than wet AMD * Fibrosis or atrophy, retinal epithelial tear in the center of the fovea in the study eye, or any condition preventing visual acuity improvement * History of retinal detachment (with or without repair) in the study eye * History of vitrectomy, trabeculectomy, or other filtration surgery in the study eye * Uncontrolled glaucoma in the study eye * Any prior treatment with photodynamic therapy or retinal laser for the treatment of wet AMD and any previous therapeutic radiation in the region of the study eye * Any previous intraocular or periocular surgery on the study eye within 6 months * Acute coronary syndrome, myocardial infarction or coronary artery revascularization, CVA, TIA in the last 6 months * Uncontrolled hypertension defined as average SBP ≥160 mmHg or an average DBP ≥100 mmHg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Type, severity, and incidence of ocular and systemic adverse events (AEs) | 104 weeks | Type, severity, and incidence of ocular and systemic adverse events (AEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in central subfield thickness (CST) and macular volume measured by SD-OCT | 104 weeks | Change in central subfield thickness (CST) and macular volume measured by SD-OCT |
| Percentage of subjects requiring anti-VEGF injections over time | 104 weeks | Percentage of subjects requiring anti-VEGF injections over time |
| Change in best corrected visual acuity (BCVA) | 104 weeks | Change in best corrected visual acuity (BCVA) |
| Percentage of subjects without intraretinal fluid over time | 104 weeks | Percentage of subjects without intraretinal fluid over time |
| Percentage of subjects without subretinal fluid over time | 104 weeks | Percentage of subjects without subretinal fluid over time |
| Mean number of anti-VEGF injections over time | 104 weeks | Mean number of anti-VEGF injections over time |
Countries
United States
Outcome results
None listed