Efficacy, Safety, pharmacokinetiсs, Immunogenicity of GNR-067 and Lucentis®

Inclusion Criteria:

1. Men and women aged 50 years and older;
2. The signed informed consent obtained from the patient, or, in cases of severe visualimpairment in the patient, with the participation of an impartial witness, prior toany study-related procedures. Ophthalmic inclusion criteria (must be present in one eye, which will be consideredthe examined eye)
3. The previously diagnosed neovascular (wet) age-related macular degeneration confirmedat the Screening Visit: untreated, except for food supplement, vitamins, mineral additives (one examined eyein one patient); Types 1 and 2 (occult and classical) choroidal neovascularization (CNV) with the following activity signs: accumulation of intraretinal and/orsubretinal (under the neurosensory retina or pigment epithelium) fluid, extravasal dyeexit from the newly formed vessels, and the presence of a subfoveal and/or juxtafovealmembrane and the presence of CNV foci of more than 50% of the total lesion area;
4. The best-corrected visual acuity within a range from 34 to 83 letters (20/200 to 20/25) measured using the ETDRS chart Early Treatment Diabetic Retinopathy StudyResearch Group protocol (chart at a distance of 4 m) before pupil dilation;
5. The willingness and ability of the patient to perform all planned study visits andprocedures (according to the Investigator);
6. IOP ≤21 mmHg (actual);
7. An ECG within normal values or clinically insignificant findings.

Exclusion Criteria:

1. Medical history of CNV treatment with intravitreal injections of VEGF inhibitors (ranibizumab, bevacizumab, aflibercept, or pegaptanib, etc.), or any otherinvestigational poducts into the examined eye;
2. Medical history of subretinal laser photocoagulation or other surgical interventionsfor ARMD in any eye;
3. Preexisting and current lesions, diseases, or interventions in the eyes.: In the examined eye: Keratoplasty or corneal dystrophy Capsulotomy performed 4 weeks prior to screeningAphakia, vitrectomy Presence of a macular hole at any stage Past rhegmatogenousretinal detachment Any other past intraocular surgical interventions in the examinedeye (including cataract extraction in the examined eye) within 3 months prior to theScreening Visit In any eye: Choroidal neovascularization in any eye due to reasons not related to ARMD (forexample, multifocal choroiditis, ocular histoplasmosis syndrome, injury, etc.) Pastidiopathic or autoimmune uveitis in any eye Scleromalacia Diagnosed diabeticretinopathy Current conditions and diseases identified at the screening stage: High degree myopia (over 8 diopters) in any eye; Presence of progressive glaucoma (intraocular pressure ≥21 mmHg against performed antihypertensive glaucoma therapy) oroptic neuropathy that affect or endanger the central field of view in the examined eyeat the screening stage; Subretinal hemorrhage and/or hemorrhage in the retinal tissueoccupying ≥50% of the total affected area in the examined eye; Presence of a rupture (solution of continuity) of the retinal pigment epithelium (RPE) also extending to themacula in any eye; A scar or subretinal fibrosis in the macular area occupying morethan 50% of the total affected area in any eye; Presence of vitreomacular traction orepiretinal membrane significantly affecting central vision; Other than ARMDprogressive retinal diseases in the examined or fellow eye that may complicate theassessment of visual acuity; The total size of the lesion is more than 12 disc areas (DA: 30.5 mm2 including areas occupied by blood, neovascularization, or fibrosis),based on a FAG performed at screening; Confirmed or assumed (within 28 days prior tothe Screening Visit) intraocular, extraocular, and periocular inflammation orinfection in any eye.
4. Any intravitreal injections of corticosteroids (e.g., triamcinolone acetonide) for ≥30days in a row in the examined eye 90 days prior to the Screening Visit and/orinjection of an intravitreal corticosteroid implant with a gradual release of themedicinal product into the examined eye within 180 days prior to the Screening Visit;
5. Known allergic reactions and/or hypersensitivity to Lucentis® (ranibizumab) or anyingredients of GNR-067;
6. Known allergic reactions and/or hypersensitivity to fluorescein sodium (forinjections);
7. Uncontrolled arterial hypertension (BP ≥180/90 mmHg);
8. Diseases of the immune and endocrine system, not controlled by drug therapy (includingdecompensated diabetes mellitus and thyroid diseases);
9. Medical history or current (active cancer)of oncological diseases with the exceptionof cured basal cell carcinoma;
10. Vaccination (any vaccine) within 30 days prior to the Screening Visit and/or the needfor vaccination during the study period;
11. Systemic treatment with corticosteroids (more than 10 mg of prednisolone equivalent)within 6 months prior to the Screening Visit;
12. Use of systemic medicinal products known to be toxic for the eye lens, retina, oroptic nerve during the study.
13. Medical history of a clinically significant pathology identified during the screeningperiod including, but not limited to: Unstable angina pectoris, myocardial infarction, arrhythmia requiring drug therapy,Class III or IV congestive heart failure according to the New York Heart Associationclassification within one year before the Screening Visit; Brain injury, stroke, ortransient ischemic attack within one year prior to the Screening Visit; Severe renalfailure (estimated glomerular filtration rate according to the CKD-EPI formula <40mL/min/1.73 m2); Severe hepatic impairment (serum alanine aminotransferase (ALT)and/or aspartate aminotransferase (AST) activity of 2.5 or more times higher than thelaboratory upper limit of normal (ULN), and/or the level of total bilirubin of 1.5 ormore times higher than the laboratory ULN); Variation of peripheral blood parameters: Leukocytes: <3.8 × 109/L Platelets: <100 × 109 cells/L Hemoglobin: ≥10.0 g/dL
14. Pregnancy and breastfeeding;
15. Patients who received blood or blood component transfusions within 10 days prior tothe Screening Visit;
16. History (within three years prior to the Screening Visit) of tuberculosis, alcoholism,narcotic, drug dependence and/or substance abuse, or presence of the above at theScreening stage;
17. Acute hepatitis or liver cirrhosis of any etiology; antibodies to hepatitis C or HBsAgat the Screening Visit; acquired immune deficiency syndrome or infection with humanimmunodeficiency virus (HIV) confirmed by test results;
18. Participation of the patient in any clinical studies and/or use of experimentalmedicinal products within 3 months prior to the Screening Visit.