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

Exclusion Criteria

• •1. Medical history of CNV treatment with intravitreal injections of VEGF inhibitors (ranibizumab, bevacizumab, aflibercept, or pegaptanib, etc.), or any other investigational poducts into the examined eye;
• •2. Medical history of subretinal laser photocoagulation or other surgical interventions for 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 screening Aphakia, vitrectomy Presence of a macular hole at any stage Past rhegmatogenous retinal detachment Any other past intraocular surgical interventions in the examined eye (including cataract extraction in the examined eye) within 3 months prior to the Screening Visit
• •In any eye:
• •Choroidal neovascularization in any eye due to reasons not related to ARMD (for example, multifocal choroiditis, ocular histoplasmosis syndrome, injury, etc.) Past idiopathic or autoimmune uveitis in any eye Scleromalacia Diagnosed diabetic retinopathy
• •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) or optic neuropathy that affect or endanger the central field of view in the examined eye at the screening stage; Subretinal hemorrhage and/or hemorrhage in the retinal tissue occupying ≥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 the macula in any eye; A scar or subretinal fibrosis in the macular area occupying more than 50% of the total affected area in any eye; Presence of vitreomacular traction or epiretinal membrane significantly affecting central vision; Other than ARMD progressive retinal diseases in the examined or fellow eye that may complicate the assessment 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 to the Screening Visit) intraocular, extraocular, and periocular inflammation or infection in any eye.
• •4. Any intravitreal injections of corticosteroids (e.g., triamcinolone acetonide) for ≥30 days in a row in the examined eye 90 days prior to the Screening Visit and/or injection of an intravitreal corticosteroid implant with a gradual release of the medicinal product into the examined eye within 180 days prior to the Screening Visit;
• •5. Known allergic reactions and/or hypersensitivity to Lucentis® (ranibizumab) or any ingredients of GNR-067;
• •6. Known allergic reactions and/or hypersensitivity to fluorescein sodium (for injections);
• •7. Uncontrolled arterial hypertension (BP ≥180/90 mmHg);
• •8. Diseases of the immune and endocrine system, not controlled by drug therapy (including decompensated diabetes mellitus and thyroid diseases);
• •9. Medical history or current (active cancer)of oncological diseases with the exception of cured basal cell carcinoma;
• •10. Vaccination (any vaccine) within 30 days prior to the Screening Visit and/or the need for 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, or optic nerve during the study.
• •13. Medical history of a clinically significant pathology identified during the screening period 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 Association classification within one year before the Screening Visit; Brain injury, stroke, or transient ischemic attack within one year prior to the Screening Visit; Severe renal failure (estimated glomerular filtration rate according to the CKD-EPI formula \<40 mL/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 the laboratory upper limit of normal (ULN), and/or the level of total bilirubin of 1.5 or more 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 to the 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 the Screening stage;
• •17. Acute hepatitis or liver cirrhosis of any etiology; antibodies to hepatitis C or HBsAg at the Screening Visit; acquired immune deficiency syndrome or infection with human immunodeficiency virus (HIV) confirmed by test results;
• •18. Participation of the patient in any clinical studies and/or use of experimental medicinal products within 3 months prior to the Screening Visit.