ADVM-022 Intravitreal Gene Therapy for Wet AMD

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open Label Phase 1 Study of ADVM-022 (AAV.7m8-aflibercept) in Neovascular (Wet) Age-Related Macular Degeneration

Conditions
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Wet Age-related Macular Degeneration, Neovascular Age-related Macular Degeneration

Intervention / Treatment
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* Biological: ADVM-022


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Open-label, dose-ranging clinical study to evaluate the safety and tolerability of ADVM-022 in subjects with wet AMD.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose 1<br>6E11 vg of ADVM-022 | Biological: ADVM-022<br>* ADVM-022 (AAV.7m8-aflibercept) is a recombinant, replication-deficient adeno-associated virus (AAV.7m8) gene therapy vector carrying a coding sequence for aflibercept<br>* Other names: AAV.7m8-aflibercept;|
| Experimental: Dose 2<br>2E11 vg of ADVM-022 | Biological: ADVM-022<br>* ADVM-022 (AAV.7m8-aflibercept) is a recombinant, replication-deficient adeno-associated virus (AAV.7m8) gene therapy vector carrying a coding sequence for aflibercept<br>* Other names: AAV.7m8-aflibercept;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Type, severity, and incidence of ocular and systemic adverse events (AEs) | Type, severity, and incidence of ocular and systemic adverse events (AEs) | 104 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in best corrected visual acuity (BCVA) | Change in best corrected visual acuity (BCVA) | 104 weeks | 
| Change in central subfield thickness (CST) and macular volume measured by SD-OCT | Change in central subfield thickness (CST) and macular volume measured by SD-OCT | 104 weeks | 
| Percentage of subjects requiring anti-VEGF injections over time | Percentage of subjects requiring anti-VEGF injections over time | 104 weeks | 
| Mean number of anti-VEGF injections over time | Mean number of anti-VEGF injections over time | 104 weeks | 
| Percentage of subjects without intraretinal fluid over time | Percentage of subjects without intraretinal fluid over time | 104 weeks | 
| Percentage of subjects without subretinal fluid over time | Percentage of subjects without subretinal fluid over time | 104 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CNV, Choroidal Neovascularizatio, ADVM-022, 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