A Study to Compare JL14002 to Lucentis® in Subjects With Wet Age-related Macular Degeneration (wAMD)

Prior treatment

• Previous treatment with photodynamic therapy (PDT) or any combination therapy involving PDT in either eye.
• Any intravitreal anti-VEGF therapy (e.g., bevacizumab, aflibercept, ranibizumab, conbercept) in either eye within 90 days before the first dose.
• Previous ocular surgery in the study eye, including but not limited to: macular translocation, glaucoma filtration surgery, subfoveal laser photocoagulation, vitrectomy, transpupillary thermotherapy, or any other surgery for AMD.
• Any concurrent ocular disease (other than wAMD) or history thereof in the study eye that could confound assessment of the macula or central vision (e.g., diabetic retinopathy, retinal vein occlusion, central serous chorioretinopathy, macular hole, epiretinal membrane, vitreomacular traction).
• Intraocular or periocular surgery in the study eye within 90 days before the first dose (excluding uncomplicated eyelid surgery \>28 days prior). Parafoveal laser or cataract surgery within this period is excluded.
• Current vitreous hemorrhage in the study eye or history thereof within 28 days before the first dose.
• Current or anticipated use of medications with known retinal, lens, or optic nerve toxicity (e.g., chloroquine/hydroxychloroquine, ethambutol, tamoxifen, phenothiazines).
• Positive syphilis screening \[Treponema pallidum antibody (Tp-Ab)\].
• Known positive history or positive screening for Human Immunodeficiency Virus (HIV).
  • 30.Pregnancy, lactation, or unwillingness to use highly effective contraception from screening until 180 days after last dose.
  • 31.Participation in another investigational drug/device trial within 90 days before screening (excluding vitamin/mineral studies).
  • 32.Uncontrolled major systemic illness at screening; history of stroke, myocardial infarction, or cerebral infarction within 180 days.
  • 33.Major surgery within 1 month before first dose, or presence of unhealed wounds/ulcers/fractures.
  • 34.Any other condition that, in the investigator's opinion, renders the subject unsuitable for trial participation.

Other illness

• Subretinal hemorrhage in the study eye involving the fovea, with an area ≥4 disc areas (DA) on FFA.
• Any ocular condition in the study eye that, per investigator judgment, may require treatment during the study, lead to vision loss, or preclude adequate fundus imaging/assessment (e.g., significant media opacity, pupillary miosis).
• History of corneal transplantation in the study eye.
• Active ocular infection in either eye at screening (e.g., conjunctivitis, keratitis, scleritis, endophthalmitis, uveitis).
• History of idiopathic or autoimmune-associated uveitis in either eye.
• History of severe allergic reaction to biologics, or known hypersensitivity to JL14002, ranibizumab, fluorescein/ICG, mydriatics, or related topical agents.
• Active systemic infection requiring therapy.
• Poorly controlled autoimmune disease.
• Hepatitis B: Positive for Hepatitis B surface antigen (HBsAg). Note: Subjects with positive HBsAg but undetectable Hepatitis B virus deoxyribonucleic acid (HBV-DNA) are eligible.
• Hepatitis C: Positive for Hepatitis C virus (HCV) antibody. Note: Subjects with positive HCV antibody but undetectable HCV ribonucleic acid (HCV-RNA) are eligible.

Lab values

• Any condition that, per investigator judgment, poses a high risk for complications or confounds results (e.g., uncontrolled hypertension \[SBP≥160 or DBP≥100 mmHg\], HbA1c ≥8%).
• Recent corticosteroid use meeting any of the following:
  • 1\) Study eye (intraocular/subconjunctival): Intermediate-/short-acting (e.g., triamcinolone) within 90 days; long-acting/sustained-release (e.g., dexamethasone implant) within 180 days.
  • 2\) Study eye (periocular): Injection within 28 days before screening; topical ocular use for ≥30 continuous days within 90 days.
  • 3\) Systemic: Within 5 days before screening or anticipated need during study (excluding topical, inhaled, intranasal, intra-articular, or short-term oral \[\<2 weeks\] use).
  • 24.Fellow eye BCVA \<24 letters (Snellen \<20/320) or presence of other potentially blinding conditions.
  • 25.Systemic anti-VEGF therapy within 90 days before the first dose. 26.History of malignancy within 5 years (exceptions: adequately treated basal/squamous cell skin cancer, carcinoma in situ of cervix/breast).
  • 27.Clinically significant abnormal liver or renal function:1) ALT or AST ≥2 × ULN;2) Creatinine or BUN ≥1.5 × ULN 28.Coagulopathy (PT ≥ ULN +3 sec; aPTT ≥ ULN +10 sec). 29.Positive serology for:

Other

• Presence of subfoveal fibrosis, scar, geographic atrophy, or dense subfoveal hard exudates in the study eye.
• Choroidal neovascularization (CNV) in the study eye due to causes other than wAMD (e.g., ocular histoplasmosis, pathologic myopia, angioid streaks, trauma).
• Active intraocular, extraocular, or periocular inflammation in either eye at screening.
• Aphakia (excluding pseudophakia) or rupture of the posterior lens capsule in the study eye (except status post YAG laser capsulotomy).
• Advanced glaucoma or optic neuropathy involving/threatening the central visual field in the study eye; or uncontrolled intraocular pressure (IOP ≥25 mmHg despite treatment).
• High myopia (spherical equivalent ≤ -6 diopters) in the study eye.

• 1.Ability to understand and voluntarily sign the informed consent form, and willingness to comply with all trial protocol-specified follow-up visits.
• 2.Aged 50 to 80 years (inclusive), male or female. 3.The study eye must meet all the following criteria:
• Diagnosis of wet Age-related Macular Degeneration (wAMD) with active disease at screening, defined by the presence of ≥1 of the following macular lesions:a) Intraretinal fluid; b) Intraretinal lipid exudation or subretinal fluid; c) Subretinal fluid; d) Subretinal hemorrhage; e) Retinal pigment epithelial detachment (PED).
• Best Corrected Visual Acuity (BCVA) score between 75 and 24 letters (inclusive) as measured by ETDRS chart at screening (Snellen equivalent: 20/32 to 20/320).