A Phase II/III Multicenter, Randomized, Masked, Active Comparator-Controlled Study to Evaluate the Safety and Efficacy of Two Doses of OCUL101, an Anti-VEGF and Anti-Complement C5, Bi-specific Humanized Antibody-Like “trap” in Participants with Neovascular Age-Related Macular Degeneration with or without Geographic Atrophy – STAT Study

Prior treatment

• For participants who have undergone prior refractive or cataract surgery, the preoperative refractive error should not have exceeded -8 diopters of myopia in the study eye.
• Any prior or concomitant treatment for CNV, GA or vitreomacular-interface abnormalities, including, but not restricted to, IVT treatment (e.g., anti-VEGF, complement therapy, steroids, tissue plasminogen activator, ocriplasmin, C3F8, air), periocular pharmacological intervention, argon laser photocoagulation, verteporfin photodynamic therapy, diode laser, transpupillary thermotherapy, or ocular surgical intervention in the study eye.
• Any cataract surgery or treatment for complications of cataract surgery with steroids or YAG (yttrium-aluminum-garnet) laser capsulotomy within 3 months prior to Screening in the study eye
• Any other intraocular surgery or intervention (e.g., pars plana vitrectomy, glaucoma surgery, including minimally invasive glaucoma surgery [MIGS], corneal transplant, or radiotherapy)
• Any major illness or major surgical procedure within 1 month before screening
• Active cancer within the 12 months prior to Screening except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of < 6 and a stable prostate-specific antigen for > 12 months
• Requirement for continuous use of any medications and treatments indicated in Section 6.6.1, Prohibited Therapy
• Stroke (cerebral vascular accident) or myocardial infarction within 6 months prior to Screening.
• Participation in an investigational trial that involves treatment with any drug or device (with the exception of vitamins and minerals), including gene therapy or cell therapies, within 3 months prior to Screening
• Any concurrent intraocular condition (e.g., amblyopia, aphakia, retinal detachment, cataract, diabetic retinopathy or maculopathy, or epiretinal membrane with traction) that, in the opinion of the investigator, could either reduce the potential for visual improvement or require medical or surgical intervention during the study in the study eye.
• Uncontrolled glaucoma, defined as intraocular pressure >25 mmHg while on two or more pressure lowering medications and/or will require surgical intervention or laser treatment during the study in the study eye.

Other illness

• History of idiopathic or autoimmune-associated uveitis in either eye
• Active ocular inflammation or suspected or active ocular or periocular infection in either eye at the Screening visit.
• Any history of macular pathology unrelated to AMD affecting vision or contributing to the presence of intraretinal or subretinal fluid in the study eye.
• Systemic treatment for suspected or active systemic infection at Screening. a. Ongoing use of prophylactic antibiotic therapy may be acceptable if approved after discussion with the Medical Monitor
• History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of OCUL101 or aflibercept injections, study-related procedure preparations (including fluorescein), dilating drops, or any of the anesthetic and antimicrobial preparations used by a participant during the study
• Current vitreous hemorrhage at Screening and Day 1 in the study eye.

Lab values

• History of other disease, metabolic dysfunction, physical examination finding, or historical or current clinical laboratory findings giving reasonable suspicion of a condition that contraindicates the use of the investigational drug or that might affect interpretation of the results of the study or renders the participant at high risk for treatment complications in the opinion of the investigator

Other

• CNV due to causes other than AMD, such as ocular histoplasmosis, trauma, pathological myopia, angioid streaks, choroidal rupture, or uveitis in either eye.
• Non-functioning non-study eye, defined as either: a. BCVA of hand motion or worse b. No physical presence of non- study eye (i.e., monocular)
• Uncontrolled blood pressure, defined as systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg while a participant is at rest at the Screening visit.
• Pregnancy or breastfeeding, or intention to become pregnant during the study
• Presence at screening of central serous chorioretinopathy in the study eye.
• Retinal pigment epithelial tear involving the macula.
• On FA/CFP/OCT/FAF: Inactive nAMD in the study eye.
• Spherical equivalent of refractive error demonstrating more than 8 diopters of myopia in the study eye.

• Signed Informed Consent
• Age ≥50 and ≤89 years on Day 1/Baseline
• Treatment-naive CNV secondary to AMD (nAMD), with or without geographic atrophy in the study eye.
• BCVA of 70 to 24 letters, inclusive (20/40 to 20/320 approximate Snellen equivalent), using the ETDRS protocol (see the BCVA manual for additional details) at Screening and Baseline in the study eye
• Participants with confirmed underlying geographic AMD in the study eye at Screening or Baseline will be included in the study if all of the other criterion are met
• Sufficiently clear ocular media and adequate pupillary dilatation to allow acquisition of good quality retinal images to confirm diagnosis in the study eye
• Male participants engaged in a sexual relationship with a woman of childbearing potential must be willing to use a medically accepted method of contraception from the duration of their participation in the study.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive measures that result in failure rate <1% per year during the treatment period and for at least 3 months after the final dose of study treatment