Safety and Efficacy of ADVM-022 in Treatment-Experienced Patients With Neovascular Age-related Macular Degeneration [LUNA]

Study Overview
=================
Brief Summary
-----------------
Neovascular or wet age-related macular degeneration (nAMD) is a degenerative ocular disease associated with the infiltration of abnormal blood vessels in the retina from the underlying choroid layer and is a leading cause of blindness in patients over 65 years of age. The abnormal angiogenic process in nAMD is stimulated and modulated by vascular endothelial growth factor (VEGF). Treatment of nAMD requires frequent intravitreal (IVT) injections of VEGF inhibitors (anti-VEGF) administered every 4-16 weeks. ADVM-022 (AAV.7m8-aflibercept) is a gene therapy product being developed for the treatment of nAMD and offers the potential for sustained intraocular expression of aflibercept following a single IVT injection. ADVM-022 is designed to reduce the current treatment burden which often results in undertreatment and vision loss in patients with nAMD receiving anti-VEGF therapy in clinical practice.

Detailed Description
-----------------
This Phase 2, multi-center, randomized, double-masked, parallel group study is designed to evaluate the safety, tolerability, and efficacy of a single IVT injection of ADVM-022 at one of two doses (2 × 10^11 vg/eye [2E11] or 6 × 10^10 vg/eye [6E10]) accompanied by one of four prophylactic corticosteroid treatment regimens. Up to 72 anti-VEGF treatment-experienced study participants meeting the eligibility criteria will be randomized between the 2E11 vg/eye and 6E10 vg/eye ADVM-022 doses each with 4 prophylaxis arms for a total of 8 treatment arms, and only one eye per study participant will be selected as the study eye. Safety, tolerability, and efficacy will be evaluated for a period of approximately 1 year from baseline.

Official Title
-----------------
A Multi-Center, Randomized, Double-Masked Phase 2 Study to Assess Safety and Efficacy of ADVM-022 (AAV.7m8-aflibercept) in Anti-VEGF Treatment-Experienced Patients With Neovascular (Wet) Age-related Macular Degeneration (nAMD) [LUNA]

Conditions
-----------------
Neovascular Age-related Macular Degeneration

Intervention / Treatment
-----------------
* Genetic: ADVM-022
* Genetic: ADVM-022


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female participants, ≥ 50 years of age Willing and able to provide written, signed informed consent for this study Demonstrated a meaningful response to anti-VEGF therapy Participants must be under active anti-VEGF treatment for wet AMD and received a minimum of 2 injections within 4 months prior to screening for the treatment of choroidal neovascularization secondary to nAMD in the study eye BCVA ETDRS Snellen equivalent between ≤20/25 and ≥20/320 Exclusion Criteria: Any condition that could affect the interpretation of results or render the participant at high risk of treatment complications in the opinion of the Investigator Ocular or periocular infection or intraocular inflammation in either eye within 1 month prior to or at the Randomization Visit (Day -7) Uncontrolled diabetes or HbA1c ≥ 7.0 % History or evidence of significant uncontrolled concomitant disease within 6 months of the Screening visit Any history of ongoing bleeding disorders or INR >3.0 History or evidence of macular or retinal disease other than nAMD History or evidence of retinal detachment or retinal pigment epithelium rip/tear Uncontrolled ocular hypertension or glaucoma Prior treatment with photodynamic therapy or retinal laser for the treatment of nAMD Any history of vitrectomy or any other vitreoretinal surgery within 3 months prior to the Randomization Visit (Day -7) Prior treatment with gene therapy at any time or any non-gene therapy investigational treatment or medical device in the study eye within 3 months of the Screening Visit or 5 half-lives of the investigational medicinal product

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose 1<br>A single intravitreal injection of ADVM-022 2E11 vg/eye | Genetic: ADVM-022<br>* A single IVT injection of 2E11 vg/eye ADVM-022 dose in combination with one (1) of four (4) corticosteroid treatment regimens<br>|
| Experimental: Dose 2<br>A single intravitreal injection of ADVM-022 6E10 vg/eye | Genetic: ADVM-022<br>* A single IVT injection of 6E10 vg/eye ADVM-022 dose in combination with one (1) of four (4) corticosteroid treatment regimens<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of ocular and non-ocular adverse events | Incidence of ocular and non-ocular adverse events | From Baseline to Week 52 | 
| Incidence of ocular and non-ocular adverse events | Incidence of ocular and non-ocular adverse events | From Baseline to Week 52 | 
| Mean change in best corrected visual acuity (BCVA) from Baseline | BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS) | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants from Baseline who lose/gain at least 5, 10 or 15 letters in Best Corrected Visual Acuity (BCVA) | BCVA measured by ETDRS | Week 52 | 
| Mean change in BCVA from Baseline | BCVA measured by ETDRS | Week 26 | 
| Percentage of participants who are supplemental aflibercept injection-free | Supplemental anti-VEGF treatments required post therapy | Week 52 | 
| Percentage reduction in anti-VEGF injections | Supplemental anti-VEGF treatments required post therapy to the year prior | Week 52 | 
| Mean change in Central Subfield Thickness (CST) from Baseline | To evaluate the effect of ADVM-022 on CST | Week 52 | 
| Percentage of participants without CST fluctuations > 50 μm | To evaluate the effect of ADVM-022 on CST | Week 52 | 
| Mean number of CST fluctuations > 50 μm from Baseline | To evaluate the effect of ADVM-022 on CST | Week 52 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aflibercept, Best Corrected Visual Acuity, Adverum, ADVM, ADVM-022, ADVM-022-11, Age-related macular degeneration, Wet macular degeneration, Wet AMD, Choroidal neovascularization, CNV, AAV.7m8, Anti-VEGF therapy, Gene therapy, Blindness, AAV, AAV vector, nAMD, wAMD, Eye disease, Eye diseases