A Prospective Longitudinal Analysis of Faricimab (Vabysmo 6mg) For Choroidal Neovascularization in Presumed Ocular Histoplasmosis Syndrome

Inclusion criteria

• Age ≥18 years at the time of signing the Informed Consent Form
• Ability to comply with study protocol requirements, in the investigator's judgment
• Willingness to comply with study visits and procedures for the full duration of the 52-week study period
• For women of childbearing potential: agreement to use highly effective contraception methods or practice complete abstinence during the study and for at least 3 months following the last dose of the investigational product, in accordance with local regulatory guidelines
• For men with partners of childbearing potential: agreement to use effective contraception or practice complete abstinence during the study and for at least 3 months following the last dose of the investigational product
• Presence of choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis syndrome (POHS), confirmed by funduscopic examination and supported by OCT imaging
• Best-Corrected Visual Acuity (BCVA) between 20/40 and 20/400, inclusive, using the ETDRS letter score system at screening
• Central macular subfield thickness (CST) >300 microns, as measured by spectral-domain OCT
• No prior treatment with anti-VEGF agents in the study eye within 6 months prior to screening
• No presence of other ocular diseases or conditions in the study eye that could confound visual outcomes, interfere with assessment of treatment efficacy, or pose a safety risk (see exclusion criteria)

Exclusion criteria

• Known hypersensitivity to faricimab or any of its excipients Faricimab
• Known hypersensitivity to contrast agents (e.g., fluorescein), dilating eye drops, disinfectants (e.g., iodine), anesthetics, or antimicrobial preparations used during the study
• History of other significant systemic disease, non-diabetic metabolic dysfunction, abnormal physical examination findings, or clinical laboratory abnormalities that, in the opinion of the investigator, could pose a risk to the patient, interfere with study participation, or confound interpretation of study results
• Active malignancy within 12 months prior to Day 1, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin cancer, or prostate cancer with a Gleason score ≤6 and stable PSA for >12 months
• History of stroke (cerebrovascular accident) or myocardial infarction within 12 months prior to Day 1
• Febrile illness within 1 week prior to Day 1
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of faricimab

o Women of childbearing potential must have a negative urine pregnancy test within 28 days prior to initiation and again at the baseline (Day 1) visit

• Uncontrolled hypertension, defined as systolic BP >180 mmHg and/or diastolic BP >100 mmHg at rest; a repeat measurement ≥30 minutes later on the same day is permitted if the initial reading is elevated
• Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis within 6 months prior to Day 1, or anticipated need for dialysis during the study
• Participation in another investigational trial involving treatment with any drug or device (excluding vitamins/minerals) within 3 months or 5 half-lives (whichever is longer) prior to Day 1, or during the study
• Clinically significant substance abuse within 12 months prior to screening, in the investigator's judgment
• Use of systemic immunomodulatory treatments (e.g., IL-6 inhibitors) within 6 months or 5 half-lives (whichever is longer) prior to Day 1
• Use of systemic corticosteroids within 1 month prior to Day 1
• Systemic treatment for suspected or active systemic infection

o Note: Ongoing prophylactic antibiotic therapy is allowed

• Any prior or concomitant systemic anti-VEGF treatment within 6 months or 5 half-lives (whichever is longer) prior to Day 1
• Use of systemic medications known to be toxic to the lens, retina, or optic nerve (e.g., deferoxamine, chloroquine/hydroxychloroquine, tamoxifen, phenothiazines, or ethambutol) within 6 months or 5 half-lives (whichever is longer) prior to Day 1
• Receipt of any treatment resulting in systemic immunosuppression within 6 months or 5 half-lives (whichever is longer) prior to Day 1
• Requirement for continuous use of medications or therapies listed as prohibited by the protocol

Ocular exclusion criteria for study eye:

Patients will be excluded if the study eye meets any of the following criteria:

• Prior intravitreal anti-VEGF therapy within 6 months prior to Day 1 Faricimab
• Presence of significant ocular pathology other than POHS that may affect visual outcomes or confound study assessments (e.g., retinal vein occlusion, proliferative diabetic retinopathy, central serous chorioretinopathy, or advanced age-related macular degeneration)
• Presence of a visually significant cataract or other media opacity expected to affect visual acuity or interfere with fundus imaging or OCT evaluation
• Active intraocular inflammation (e.g., iritis, uveitis, vitritis) in the study eye at screening
• History of endophthalmitis in the study eye
• Intraocular pressure >25 mmHg in the study eye at screening despite maximum tolerated medical therapy
• History of vitrectomy or glaucoma filtration surgery in the study eye
• Any planned ocular surgery in the study eye during the course of the study

Ocular exclusion criteria for non-study eye:

Patients will be excluded if the non-study eye meets any of the following criteria:

• Presence of any ocular condition that could interfere with study assessments or the safety of the patient, including but not limited to:

• Active ocular infection or inflammation
• Uncontrolled glaucoma or intraocular pressure ≥ 25 mmHg despite treatment
• Advanced diabetic retinopathy requiring immediate treatment
• Significant media opacity preventing adequate fundus examination or imaging (e.g., dense cataract, vitreous hemorrhage)
• History of vitrectomy or ocular surgery in the past 3 months
• Any condition likely to require intraocular injections or ocular surgery during the study period
• Any known hypersensitivity or allergy to components of faricimab or agents used in ocular procedures (e.g., fluorescein dye, dilating drops)
• Any ocular comorbidity that, in the investigator's opinion, could confound the evaluation of the study eye or impact patient safety