A Phase II Trial of G01 Eye Drops for Glaucomatous Optic Neuropathy

A Randomized, Double-Masked, Placebo-Controlled Phase II Clinical Trial Evaluating the Efficacy and Safety of G01 Eye Drops in the Treatment of Optic Nerve Injury Associated With Open-Angle Glaucoma

This is a randomized, double-masked, placebo-controlled Phase II clinical trial. The primary objective is to explore the efficacy of G01 Eye Drops in the treatment of optic nerve injury associated with open-angle glaucoma, providing supportive evidence for the design of subsequent clinical trials. The secondary objectives are to evaluate the safety, pharmacokinetic profiles, and immunogenicity of G01 Eye Drops in the target patient population.

Eligible patients with open-angle glaucoma and concomitant optic nerve injury will be randomized to receive either topical G01 Eye Drops or matched placebo. Multiple assessments of efficacy, safety, pharmacokinetics (PK), and immunogenicity are conducted at predefined time points following the first administration of the study drug.

The primary efficacy endpoint is the change from baseline in visual field mean deviation (MD) at Day 168. Secondary efficacy endpoints include changes from baseline in visual field MD at Days 28, 84, 252, and 336, as well as changes from baseline in retinal nerve fiber layer (RNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness, and P100 wave amplitude and latency of pattern visual evoked potential (PVEP) at Days 28, 84, 168, 252, and 336.

Additional secondary endpoints encompass pharmacokinetic characterization through plasma and tear drug concentration measurements, evaluation of anti-drug antibody (ADA) positive rates and neutralizing antibody levels, and comprehensive safety assessments throughout the study, including adverse events, vital signs, physical examinations, laboratory tests, and ophthalmic evaluations. All participants will complete the scheduled assessments according to the protocol to systematically evaluate the overall clinical profile of G01 Eye Drops.

Inclusion Criteria:

• Age from 18 to 80 years (inclusive) at the time of signing the informed consent form, regardless of gender.
• Diagnosis of primary open-angle glaucoma (POAG) in one or both eyes.
• Goal eye demonstrates disease progression as shown by Guided Progression Analysis (GPA) visual field testing at screening.
• Mean Deviation (MD) of the visual field in the goal eye ≥-16 dB and ≤-3 dB.
• Best-corrected visual acuity of the goal eye ≥0.3; spherical equivalent refraction ≥-8 D (spherical equivalent = spherical refraction + 1/2 cylindrical refraction) OR axial length ≤28 mm in the goal eye.
• Intraocular pressure of the goal eye ranges from 10 mmHg to 21 mmHg (inclusive) under hypotensive medication, post-glaucoma surgery, or no medication; and the intraocular pressure is judged stably controlled by the investigator.
• Subjects and their partners agree to use effective physical and/or pharmacological contraception from screening through 3 months after study completion; no plan for sperm/egg donation or pregnancy.
• Voluntarily sign the informed consent form for participation in this clinical trial and comply with investigator-provided instructions.

Exclusion Criteria:

• Goal eye diagnosed as angle-closure glaucoma, glaucomatocyclitic crisis, ocular hypertension, or secondary glaucoma.
• Active herpetic keratitis in the goal eye within 1 year prior to screening, or receiving antiviral therapy at screening.
• Active or recurrent ocular infection in either eye that may interfere with trial evaluations (e.g., iridocyclitis, conjunctivitis, keratitis, uveitis, endophthalmitis).
• Disease in either eye preventing adequate examination of the fundus or anterior segment.
• Fundus disorders in the goal eye that may cause severe visual loss or interfere with efficacy/safety assessments (e.g., pathological myopia, diabetic retinopathy, central retinal vein/artery occlusion, retinal detachment, retinitis pigmentosa, non-glaucomatous optic neuropathy, choroidal melanoma, hematological or vascular diseases).
• Monocular subjects.
• Ocular infection or corneal-iris-lens lesions in the goal eye judged by the investigator to interfere with efficacy or safety evaluations of the study.
• Corneal surgery on the goal eye within 3 months before screening (e.g., PRK, LASIK, SMILE, corneal cross-linking, radial keratotomy); or other conditions affecting intraocular pressure measurement (e.g., corneal edema, corneal scar, keratoconus).
• History of retinal laser surgery covering the macular region in the goal eye.
• Intraocular surgery on the goal eye (e.g., cataract surgery, fundus surgery) or ocular trauma within 3 months before screening; or planned ocular surgery during the study period.
• Glaucoma laser therapy (e.g., laser trabeculoplasty) performed on the goal eye within 1 year prior to screening.
• Filtering surgery for glaucoma on the goal eye within 1 year prior to screening (e.g., trabeculectomy, non-penetrating trabeculectomy, glaucoma drainage device implantation, cyclophotocoagulation).
• Known or suspected allergy to any component of the study drug or placebo.
• Initiation of neurotrophic medications within 28 days before screening or anticipated during the trial (e.g., nerve growth factor other than study drug, brimonidine eye drops, coenzyme Q, ginkgo biloba extract, citicoline, nicotinamide, mecobalamin, autologous serum eye drops, deproteinized calf blood extract-related preparations).
• Discontinuation period of prior growth-factor-based therapy does not exceed 5 half-lives AND/OR 14 days (the longer of 5 half-lives and 14 days shall be applied).
• Unwilling or unable to discontinue contact lens wear (including cosmetic contact lenses) throughout the study.
• Receiving systemic corticosteroids or other immunosuppressive agents.
• Poorly-controlled hypertension: systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥100 mmHg despite pharmacological treatment.
• Severe cardiovascular, hepatic, renal, or hematological disorders; poorly-controlled diabetes (random blood glucose >11.1 mmol/L at screening, HbA1c >8%, or insulin-dependent glycemic control).
• Positive for HBeAg, HCV-Ab, HIV antibody, or TP-Ab.
• Unable to complete trial procedures due to severe psychiatric or language barriers.
• Participation in another clinical trial within 30 days prior to screening.
• Cigarette consumption >10 cigarettes per day within 3 months before screening, or alcohol intake >14 alcohol units per week (1 unit =10 mL ethanol =200 mL 5%-ABV beer =25 mL 40%-ABV spirits =83 mL 12%-ABV wine).
• History of malignancy (excluding basal cell carcinoma), unless treatment was completed at least 2 years prior to screening.
• Ongoing chemotherapy.
• History of drug dependence, drug abuse, or illicit-drug use within 5 years prior to screening.
• Female subjects who are pregnant, lactating, or with positive serum pregnancy test.
• Subjects deemed unsuitable for participation by the investigator.