Biomarkers, Effectiveness, and Safety of Aflibercept 8mg Modified Fixed Dose Regimen in Treatment-Naïve nAMD Patients

Prior treatment

• Patients who have received other investigational treatments (including anti-VEGF, corticosteroids, laser photocoagulation treatments \[panretinal photocoagulation or macular photocoagulation\], and photodynamic therapy \[PDT\]) or approved nAMD drugs/therapies;
• Patients with allergies or hypersensitivity reactions to any component/excipient of the investigational product;
• Uncontrolled hypertension (defined as systolic blood pressure \>160 mmHg or diastolic blood pressure \>95 mmHg). Subjects may be treated with up to three known antihypertensive drugs to achieve adequate blood pressure control. This restriction applies to drugs that can be used for treating hypertension, even if the primary purpose of taking the drug for the subject is not blood pressure control. Any medication known to affect blood pressure must have a stable regimen for 12 weeks prior to screening;
• Any intraocular disease that the investigator believes may reduce vision improvement or require medical or surgical intervention during the study (such as amblyopia, aphakia, retinal detachment, cataract, diabetic retinopathy or maculopathy, epiretinal membrane with traction):
  • Presence of vitreous hemorrhage during the screening or baseline period;
  • Uncontrolled glaucoma (intraocular pressure still \>25 mmHg despite anti-glaucoma medication);
  • Any cataract surgery or treatment for cataract surgery complications with steroids or yttrium-aluminum garnet (YAG) laser capsulotomy within 3 months prior to Day 1 of the study;
  • Any prior intraocular surgery (e.g., vitrectomy, glaucoma surgery, corneal transplantation, or radiation therapy);
  • Prior periocular or intravitreal drug injections (including anti-VEGF agents) for other retinal diseases;
  • Presence of intraocular inflammation/infection in any eye within 12 weeks prior to the screening visit;
  • History of idiopathic or autoimmune-related uveitis in the study eye.

Other illness

• Any condition that, in the opinion of the investigator, may affect the patient's ability to provide informed consent, comply with the study protocol, complete the study according to study procedures, or for which the patient's participation may affect the study results or their own safety; Exclusion criteria for study eye
• Any eye with diabetic retinopathy (DR), diabetic macular edema (DME), or any retinal vascular disease other than nAMD;
• Presence of extraocular/periocular infection or inflammation in any eye during the screening or baseline period;
• Fluorescein angiography (FA)/fundus photography (FP) showing:
  • Total lesion area (including hemorrhage, scarring, and neovascularization) greater than 12 disc areas (30.5 mm²);
  • Fibrosis or atrophy \>50% of the total lesion area, and/or involving the fovea.

Lab values

• History of other diseases, metabolic dysfunctions, abnormal physical examinations, or clinical laboratory abnormalities that reasonably suggest a contraindication to the investigational drug, may interfere with the interpretation of study results, or could place the patient at high risk for treatment-related complications;

Other

• Presence of retinal pigment epithelium (RPE) tear or rupture, scarring, fibrosis, or atrophy involving the fovea;

• Patients who fully understand the content, procedures, and possible adverse events (AEs) of this study and are able to provide written informed consent;
• Male or female patients aged ≥50 years at the time of signing the informed consent;
• Women of childbearing potential (WOCBP) must agree to use dual contraception during the study and for 4 months after discontinuation of study treatment, consisting of one medically recognized contraceptive method with a failure rate of less than 1% per year (see Appendix 1 for Contraceptive Measures, Definitions and Requirements for Women of Childbearing Potential) combined with a barrier method (e.g., condom). Women who have undergone surgical sterilization (such as hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or menopause for more than 1 year are considered not of childbearing potential. Women of childbearing potential must have a negative pregnancy test at screening and must not become pregnant, breastfeed, lactate, or plan pregnancy, breastfeeding, or egg donation during the study and for 4 months after discontinuation of study treatment;
• Male subjects whose partners are of childbearing potential must agree to use dual contraception during the study and for 4 months after the end of treatment, consisting of one medically recognized contraceptive method with a failure rate of less than 1% per year (see Appendix 1 for Contraceptive Measures, Definitions and Requirements for Women of Childbearing Potential) combined with a barrier method (e.g., condom), and must agree not to donate sperm during the study and for 4 months after the end of treatment.
• Subjects included in this study must meet all of the following ocular inclusion criteria for the study eye:
• Have sufficiently clear ocular media and adequately dilated pupils to obtain high-quality retinal images for diagnosis;
• Untreated nAMD with active subfoveal choroidal neovascularization (CNV), with total CNV area accounting for more than 50% of the total lesion area.
• SD-OCT examination showed the presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF) in the foveal center of the retina.
• During the screening and baseline periods, BCVA scores measured using the ETDRS visual acuity chart at an initial testing distance of 4 meters ranged from 78 to 24 ETDRS letters (inclusive) (approximately equivalent to Snellen visual acuity 20/32 to 20/320), and the vision loss was caused by nAMD.