A Study to Compare GNR-139 and Eylea® in Patients With nAMD

• 1. Men and women aged ≥ 50 years at the time of signing the Informed Consent Form.

  2. Written informed consent obtained from the patient or, in the case of severe visual impairment in the patient, with the participation of an impartial witness, prior to the initiation of any study-related procedures.

  3. Willingness of a patient of childbearing potential to adhere to adequate methods of contraception throughout the study (from the signing of the Informed Consent Form) and for at least 120 days after the last IVI of aflibercept.

  4. Patient's willingness and ability to adhere to the schedule of visits and perform the procedures required by the protocol.

Ophthalmic inclusion criteria:

Study eye 5. Previously untreated active MNV secondary to nAMD (i.e., presence of FFA leakage, as well as IRF and/or SRF and/or subretinal hyperreflective material and/or serous or fibrovascular RPE detachment based on OCT data) meeting the following criteria: 5.1. Any subtype of secondary MNV (classic, occult, predominantly classic or minimally classic, with a classic component, retinal angiomatous proliferation, and polypoidal choroidal vasculopathy); 5.2. Sub foveal or juxta foveal location, but with a sub foveal component related to MNV activity (e.g., IRF or SRF detected by OCT, or RPE detachment); 5.3. Total lesion area (including hemorrhage, scarring, and neovascularization) ≤ 12 disc areas (DA) based on FFA data; 5.4. Total MNV area must comprise ≥ 50 % of the total lesion area based on FFA results, including all subtypes of neovascular AMD (nAMD); 5.5. Presence of IRF and/or SRF involving the central sub foveal zone (1 mm diameter), or presence of sub retinal hyperreflective material or neovascular RPE detachment in this zone based on OCT data.

6. BCVA score between 74 and 24 letters (inclusive) on the ETDRS chart at screening and prior to randomization on Day 1 (before pupil dilation).

7. CST at screening ≥ 300 µm based on OCT data.

Exclusion Criteria:

• 1. Known hypersensitivity to aflibercept or to any of the excipients contained in GNR-139 or Eylea®.

  2. Known hypersensitivity to sodium fluorescein for injection used for FFA. 3. Uncontrolled arterial hypertension at screening: systolic blood pressure > 160 mmHg or diastolic blood pressure > 95 mmHg.

  4. Traumatic brain injury, transient ischemic attack, or stroke within 180 days prior to randomization.

  5. Unstable angina, myocardial infarction, clinically significant arrhythmia (e.g., atrial fibrillation Class III-IV according to the modified European Heart Rhythm Association (EHRA) scale), or congestive heart failure Class III or IV according to the New York Heart Association (NYHA) classification within 180 days prior to randomization.

  6. History or current malignancy (except for adequately treated basal cell carcinoma, cervical carcinoma in situ, or any malignancy with complete remission for at least 5 years).

  7. History of a medical condition or any disease (somatic, neurological, and/or psychiatric) that, in the opinion of the investigator, is a contraindication to the administration of the investigational or reference medicinal product, or may contribute to the misinterpretation of study results, or places the patient at high risk of developing complications during treatment (e.g., history of organ transplantation, immunocompromised status, etc.) and/or may interfere with the scheduled study visits.

  8. Blood or blood component transfusion within 10 days prior to signing the Informed Consent Form and/or at Screening.

  9. History of tuberculosis (within 3 years prior to signing the informed consent form) and/or at screening; history of alcoholism, drug dependence, or substance abuse.

  10. Acute hepatitis or liver cirrhosis of any etiology. 11. Positive test results for HIV, hepatitis B and/or C. 12. Participation in any clinical studies and/or use of an investigational medicinal product within 90 days prior to signing the Informed Consent Form.

  13. History of systemic anti-angiogenic therapy (e.g., use of anti-angiopoietin, bevacizumab, aflibercept, ranibizumab, pegaptanib, cetuximab, panitumumab, etc.).

  14. Systemic use of glucocorticosteroids within 180 days prior to randomization (more than 10 mg of prednisone equivalent received daily).

  15. Pregnancy or breast-feeding.

Ophthalmic criteria:

Study eye:

16. Causes of MNV other than nAMD (e.g., ocular histoplasmosis, multifocal choroiditis, angioid streaks, history of choroidal rupture, pathologic myopia, post-traumatic MNV, etc.).

17. Irreversible structural damage involving the foveal zone (e.g., subretinal fibrosis or atrophy comprising > 50 % of the total lesion area, or macular ischemia).

18. RPE tear involving the center of the macula. 19. Sub- or intraretinal hemorrhage comprising ≥ 50 % of the total lesion area, or subfoveal hemorrhage with a size ≥ 1 disc area (DA).

20. Uncontrolled glaucoma likely to progress during the study, or glaucoma with uncompensated IOP during therapy (IOP ≥ 25 mmHg despite treatment with anti-glaucoma medications).

21. Any concomitant macular disorder other than AMD that, in the opinion of the investigator, may affect central vision or the efficacy of the treatment administered, including severe epiretinal fibrosis with a significant tractional component, macular telangiectasia, etc.

22. History of Stage 2 or higher macular holes. 23. Aphakia or pseudophakia with absence of the posterior lens capsule (except for cases of YAG capsulotomy performed more than 30 days prior to signing the Informed Consent Form).

24. Myopia with a spherical equivalent ≥ 8 diopters prior to any surgical intervention.

25. Significant opacities of the optical media (including cataract) interfering with BCVA assessment, fundus photography, or OCT.

26. Any concomitant intraocular disease of the study eye (e.g., glaucoma, cataract, or diabetic retinopathy) that, in the opinion of the investigator, will either require surgical intervention during the study to prevent or treat potential vision loss resulting from such disease, or will affect the interpretation of study results.

27. Use of prohibited medications and/or treatment methods: 27.1. Prior treatment of the study eye with verteporfin (photodynamic therapy), transpupillary thermotherapy, radiation therapy, or laser retinal treatment (e.g., panretinal laser photocoagulation, macular laser photocoagulation, or focal laser photocoagulation).

27.2. History of vitrectomy, macular surgery, or any other surgical intervention in the structures of the study eye secondary to AMD.

27.3. History of corneal transplantation. 27.4. Prior vitreoretinal surgery and/or scleral buckling. 27.5. Any other intraocular surgical intervention (including cataract surgery) in the structures of the study eye within 90 days prior to signing the Informed Consent Form.

27.6. Any prior anti-angiogenic therapy (e.g., anti-angiopoietin, bevacizumab, aflibercept, ranibizumab, pegaptanib, etc.) or treatment of AMD with any investigational medicinal product.

27.7. YAG capsulotomy in the study eye within 30 days prior to signing the Informed Consent Form.

27.8. Intraocular or periocular administration of glucocorticosteroids within 120 days prior to randomization, or any treatment using an intraocular implant, gene therapy, or cell therapy at any time.

27.9. Use of topical (eye drops) glucocorticosteroids for ≥ 30 consecutive days or for ≥ 60 non-consecutive days within 90 days prior to signing the Informed Consent Form.

27.10. Use of medicinal products with established toxicity to the lens, retina, or optic nerve, including deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines, vigabatrin, and ethambutol, within 60 days prior to signing the Informed Consent Form.

27.11. History of ocriplasmin use.

Fellow eye:

28. Any ocular disease, including AMD, that, in the opinion of the investigator, may require anti-angiogenic therapy within 8 weeks after randomization (aflibercept IVIs will be permitted after Week 8 procedures have been performed).

29. Use of prohibited medications and/or treatment methods: 29.1. Any prior anti-angiogenic therapy (e.g., anti-angiopoietin, bevacizumab, aflibercept, ranibizumab, pegaptanib, etc.) or treatment of AMD with any investigational medicinal product within 180 days or 5 t1/2 (whichever is longer) prior to signing the informed consent form.

29.2. Any treatment using an intraocular implant, gene therapy, or cell therapy at any time.

29.3. Use of medicinal products with established toxicity to the lens, retina, or optic nerve, including deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines, vigabatrin, and ethambutol, within 60 days prior to signing the informed consent form.

Both eyes:

30. History and/or presence at screening of clinical manifestations of diabetic retinopathy (except for mild non-proliferative diabetic retinopathy), DME, or any other retinal vascular disease (RVO, etc.).

31. Active neovascularization of the iris, vitreous hemorrhage, or tractional retinal detachment.

32. History of idiopathic or autoimmune uveitis. 33. Active or suspected periocular, extraocular, or intraocular infection, including infectious blepharitis, keratitis, scleritis, or conjunctivitis, within 14 days prior to signing the informed consent form and/or at screening.