Eligibility Criteria
Inclusion Criteria:
* Participant agrees not to participate in another interventional study until the 52-week visit has been completed.
* Participant is able and willing to comply with the study requirements and capable of completing the assessments, including all scheduled visits.
* Participant has open-angle glaucoma (OAG) defined as rate of MD ≤ -0.5 dB/year and consisting of all of the following:
* Presence of glaucomatous VF defects in the study eye with corresponding damage to the optic nerve head (ONH) (confirmed by an independent central image reading center at screening)
* An open iridocorneal drainage angle observed on gonioscopy (Shaffer grade ≥ 3)
* Moderate to advanced VF loss, assessed by standard automated perimetry, and confirmed by the central image reading center and in the study eye:
* Phase 1 - Dose-Escalation part: advanced VF loss, defined as MD between -12 and -20 dB
* Phase 2 - Dose-Expansion part: moderate to advanced VF loss, defined as MD between -6 and -20 dB
* At least 3 reliable VF tests (≤ 33% FLs and ≤ 15% FP) within the preceding 84 months, confirmed by the central image reading center, and excluding fields obtained before incisional glaucoma or cataract surgeries
* Evidence of VF function in at least 1 quadrant in the study eye
* BCVA ≥ 20/200 (≥ 35 ETDRS letters) at screening and confirmed on day 1 in the study eye
* At least 3 consecutive reliable optical coherence tomography (OCT) scans (peripapillary RNFL, GCC/macula) in the study eye within the preceding 84 months, confirmed by the central image reading center.
* Participant must have an IOP ≤ 21 mmHg on current therapy in the study eye (or participant's IOP is considered well controlled and will not require any additional medical or surgical treatment in the next 12 months).
* Female participant is not pregnant and at least 1 of the following conditions apply:
* Not a women of childbearing potential (WOCBP) o. WOCBP who has a negative serum pregnancy test at screening, or urine pregnancy test on day 1, agrees to follow the contraceptive guidance from the time of informed consent.
* Female participant must not be breastfeeding or lactating starting at screening and throughout the study period.
* Female participant must not donate ova starting at first administration of study intervention and throughout the study period.
* Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period.
* Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period.
* Male participant must not donate sperm during the treatment period (up to week 52).
Exclusion Criteria:
* Participant has other optic nerve or retinal degenerative disease-causing vision loss, irrespective of whether it is currently treated or untreated.
* Participant has other known or suspected molecular diagnosis of macular, retinal, or optic nerve disease (e.g., pathogenic mutations in other genes) that could confound the interpretation of the outcome of the study, that could cause a concomitant retinal disease and/or point to an alternate etiology of macular or optic nerve disease.
* Participant has visually significant cataract in the study eye.
* Participant has active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis (mild stable blepharitis is permitted).
* Participant is expected to require a change in IOP-lowering treatment within 6 weeks of screening and/or is anticipated to require a change in IOP-lowering treatment during the study in the study eye.
* Participant has history of
* closed or narrow angle (Shaffer grade ≤ 2), pigment dispersion, uveitic glaucoma, or congenital glaucoma
* cyclophotocoagulation laser treatment for glaucoma in the study eye
* ocular herpetic disease (including herpes simplex and zoster viruses) or disseminated/visceral herpes zoster infection
* allergy to fluorescein or povidone iodine
* history of steroid response (historic evidence of IOP increase with corticosteroid use)
* Participant has presence of IOI (≥ trace anterior chamber \[AC\] cell or flare), has active or has a history of idiopathic or autoimmune-associated uveitis in either eye.
* Participant has evidence of corneal opacification or lack of optical clarity in the study eye.
* Participant has refractive error greater than 8 diopters of spherical equivalent at screening in the study eye.
* Participant has choroidal neovascularization, central serous retinopathy, or any other type of retinal degeneration/diseases that may interfere with the study procedures, evaluations and outcome assessments.
* Participant has undergone any laser or intraocular surgery (i.e., cataract surgery or minimally invasive glaucoma surgery) in the study eye within 12 weeks and/or yttrium aluminum garnet capsulotomy within 4 weeks prior to screening.
* Participant has a history of vitrectomy surgery in the study eye.
* Participant has a history of, or currently has, optic neuropathy not due to glaucoma, including traumatic or anterior ischemic optic neuropathy.
* Participant has presence of any other concurrent ocular disease in the study eye that would affect or confound study outcomes.
* Participant has any of the following medical conditions
* diabetes mellitus hemoglobin A1c (HbA1c) value of \> 7% at screening, with the following exception: If the HbA1c value is \> 7% and the participant has a normal creatinine, has no diabetic retinopathy, or diabetic macular edema, then the participant may be enrolled at the discretion of the investigator after consultation with the medical monitor
* uncontrolled hypertension defined as an average systolic blood pressure \> 160 mmHg or an average diastolic blood pressure \> 100 mmHg (second set of measurements is permitted if the first average exceeds the values during the same visit). Additional repeat measurement may be obtained within the screening window
* history of malignancy other than basal cell carcinoma, unless it was treated successfully at least 2 years prior to inclusion in the study
* history of multiple sclerosis or other severe autoimmune conditions
* history of uncontrolled hepatitis, pancreatitis, cirrhosis, asthma, liver/kidney/heart failure, or uncontrolled thyroid disease or intracranial hypertension
* Participant is currently receiving systemic steroids (other than those related to the study), chemotherapy, immunosuppressive medications, monoclonal antibodies, or glucagon-like peptide-1 treatment.
* Participant is currently using drugs with known ocular toxicity or confounding effects on VF assessments (including but not limited to hydroxychloroquine \[Plaquenil\], chloroquine, amiodarone, ethambutol, isoniazid, anticholinergics, sulfonamides \[including TMP-SMX/Bactrim\], and linezolid) unless these were stopped prior to screening and all possible ocular reactions were completely resolved without sequelae.
* Participant has received any prior treatment including gene therapy, stem cell therapy, surgical implantation of prosthetic retinal chips, or prior IVT treatment for any indication in either eye that may be considered to potentially interfere with the study participation or its conduction.
* Participant is currently participating in an interventional clinical study or has received an investigational agent by ocular or systemic administration within 3 months or 5 half-lives, whichever is longer prior to the screening.
* Participant has any severe acute or chronic medical condition, psychiatric condition, physical examination finding or laboratory abnormality may interfere with the study procedures, evaluation and outcome assessments and would make the participant unsuitable for study participation.