Study of AR-14034 in Participants With Neovascular Age-Related Macular Degeneration (nAMD)

A Phase 1/2 Two-Stage Dose Escalation and Randomized Parallel-Group Study to Evaluate the Safety, Preliminary Treatment Effects, and Durability of AR-14034 Sustained Release Implant Compared to Intravitreal Anti-Vascular Endothelial Growth Factor Treatment in Participants With Neovascular Age-Related Macular Degeneration

The primary purpose of this study is to evaluate the safety and durability of single- and repeat administration of AR-14034 Sustained Release (SR) in subjects with neovascular age-related macular degeneration (nAMD).

This study will be conducted in two stages. Stage 1 is a 48-week, dose-escalation, open-label evaluation of AR-14034 SR. Two cohorts will be enrolled, for an approximate total of 10 subjects. Subjects will receive AR-14034 SR in one of two dose levels and attend visits through Week 48 for assessment of safety and preliminary treatment effects.

Stage 2 is a 56-week (plus extension) double-masked, active comparator, randomized, parallel group evaluation of AR-14034 SR compared with aflibercept. Approximately 130 subjects will be enrolled and randomized 2:2:1 to AR-14034 SR one injection, AR-14034 SR two injections, or aflibercept dosed as labelled. Subjects will attend visits through Week 56 for assessment of safety and treatment effects. A 16-week open label extension phase will be conducted thereafter.

Key Inclusion Criteria [Stage 1 and Stage 2]:

• Presence of an active choroidal neovascularization (CNV) lesion secondary to age-related macular degeneration (AMD);
• Best corrected visual acuity (BCVA) between 80 and 35 letters (20/25 to 20/200 Snellen equivalent) in the study eye;
• BCVA greater than 20 letters (approximately 20/400 Snellen equivalent) in the non-study eye;
• Media clarity and pupillary dilation in the study eye sufficient for all planned study procedures;
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol;
• Other protocol-specified inclusion criteria may apply.

[Stage 1]:

• Greater than or equal to 3 and less than or equal to 6 prior treatments of an ocular anti-VEGF medication within the 8 months prior to Screening in the study eye, with demonstrated anatomic response, as assessed by the Investigator.

[Stage 2]:

• Treatment-naïve, or diagnosis of exudative neovascular age-related macular degeneration (nAMD) in the study eye.

Key Exclusion Criteria [Stage 1 and Stage 2]:

• History or current ocular disease in the study eye other than nAMD, that, might require medical or surgical intervention during the study;
• Structural damage to the macula that is likely to preclude improvement in visual acuity in the study eye after resolution of the nAMD;
• Any active intraocular or periocular infection or active intraocular inflammation;
• Treatment with ocular anti-VEGF product in the study eye within 28 days before Week 1 [Stage 1] or within 56 days before Screening [Stage 2].
• Uncontrolled glaucoma in the study eye;
• Uncontrolled blood pressure;
• Females of child-bearing potential who are pregnant, intending to become pregnant, nursing, or who are not willing to use an acceptable form of contraception for the duration of the study;
• Other protocol-specified exclusion criteria may apply.