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

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]

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.

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.

Anti-VEGF treatment-experienced study participants meeting the eligibility criteria that 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 5 years from baseline.

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
• Vision of the study eye at Baseline: BCVA in the range of 25 - 83 ETDRS letters, inclusive (approximate Snellen equivalent visual acuity range of 20/25 - 20/320)
• Vision of the non-study eye at Baseline: BCVA ≥ 35 ETDRS letters (approximate Snellen equivalent of 20/200 or better)

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
• 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