Overview

This is a Phase 1 study, first-in-human (FIH), open label study to evaluate the safety, tolerability and identify the maximum tolerated dose (MTD) of PMC-403 and determine the recommended phase 2 dose (RP2D).

Eligibility

Inclusion Criteria:

        To be eligible for study participation, subjects must meet all of the following inclusion
        criteria.
        * Criteria for the selection of the study eye
        If both eyes meet the criteria, the study eye will be selected according to the following
        criteria:
          1. The eye with lower (severer) best corrected visual acuity (BCVA) at baseline will be
             selected as the study eye.
          2. If both eyes have the same BCVA, the right eye will be selected as the study.
               1. Male and female ≥50 years of age at the time of written informed consent.
               2. Treatment required, based on the judgment of the investigator, due to
                  insufficient therapeutic efficacy despite ≥ 3 repeated doses of anti-vascular
                  endothelial growth factor (anti-VEGF) intravitreal injection (IVT) for nAMD in
                  the study eye, and the subject's agreement to receive the study drug instead of
                  conventional standard therapy
               3. >12 weeks must have elapsed since the last dose of anti-VEGF IVT at the time of
                  screening.
               4. Active subfoveal or parafoveal choroidal neovascularization (CNV)* confirmed by
                  fundus fluorescein angiography (FFA), spectral domain-optical coherence
                  tomography (SD-OCT), and IndoCyanine Green (ICG) angiography.
                  *Active CNV (confirmed by the central reading center) is defined as the presence
                  of subretinal fluid (SRF) or intraretinal fluid (IRF) in consequence of vascular
                  leakage.
               5. The size of the entire lesion in the study eye (including blood, atrophy,
                  fibrosis, and neovascularization) must be ≤ 9-disc areas, and the area of CNV in
                  the study eye must account for ≥ 50% of the total area of the lesion, as
                  confirmed by FFA and ICG angiography.
               6. BCVA measured in the study eye must be between ≥ 23 letters and ≤ 78 letters
                  based on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart (Snellen
                  visual acuity 20/25 - 20/320).
               7. Voluntary written informed consent to study participation.
        Exclusion Criteria:
        Subjects who meet any of the following exclusion criteria are not eligible for study
        participation.
          1. At the screening visit:
               1. Uncontrolled ocular hypertension (≥ 25 mmHg) despite drug therapy;
               2. Retinal pigment epithelium (RPE) tears involving the macula;
               3. Improvement in visual acuity is not expected due to scars, fibrosis, or atrophy
                  involving the fovea;
               4. Presence of vitreous hemorrhage;
               5. Aphakia or absence of posterior capsule (with the exception of pseudophakic eyes
                  treated with laser posterior capsulotomy);
               6. Presence of any causes of CNV other than nAMD, such as ocular histoplasmosis,
                  trauma, pathological myopia, angioid streak, choroidal rupture, or uveitis; or
               7. Macular pathology that is unrelated to nAMD, but may affect visual acuity or
                  study drug treatment (e.g., macular hole, epiretinal membrane, vitreomacular
                  traction, macular telangiectasia, central serous chorioretinopathy, retinal
                  vascular occlusion, etc.).
          2. Any of the following conditions or medical history in either eye:
               1. Current or known history of at least moderate diabetic retinopathy or diabetic
                  macular edema;
               2. Active intraocular or periocular infections or inflammations (e.g., infectious
                  conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis,
                  etc.); or
               3. History of idiopathic or autoimmune uveitis.
          3. Any of the following systemic diseases:
               1. Unstable or serious cardiovascular disorders such as congestive heart failure
                  (New York Heart Association Functional Class III or IV), ventricular tachycardia
                  requiring continuous treatment, unstable angina pectoris, or critical limb
                  ischemia;
               2. Uncontrolled hypertension with systolic or diastolic blood pressure > 160/100
                  mmHg;
               3. Stroke or myocardial infarction within 24 weeks prior to screening;
               4. Dementia or neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's
                  disease) that might affect study results during the study period;
               5. History of malignant tumors within 5 years prior to screening; or
               6. Weakened immunity or requiring immunotherapy.
               7. Clinically significant liver/kidney disease or any of the following hematologic
                  test results:
                    -  Serum creatinine ≥1.5 x upper limit of normal
                    -  Aspartate transaminase (AST) or alanine transaminase (ALT) ≥2 x upper limit
                       of normal
          4. Treatment with any of the following systemic drug therapy:
               1. Systemic anti-VEGF therapy within 12 weeks prior to baseline;
               2. Systemic corticosteroids for ≥2 consecutive weeks
                    -  ≤ 10 mg/day prednisolone or equivalent for less than 2 consecutive weeks
                       will be allowed
                    -  Inhaled, nasal, and topical steroids will also be allowed
               3. Ongoing treatment with any drugs with potential toxicity to the lens, retina, and
                  optic nerves (e.g., deferoxamine, chloroquine/hydroxychloroquine, tamoxifen,
                  phenothiazines, vigabatrin, or ethambutol).
          5. Any of the following medical history (surgical or procedural):
               1. Intraocular or periocular injection of corticosteroids (e.g., triamcinolone
                  acetonide, etc.) to the study eye within 24 weeks prior to screening;
               2. Intraocular surgery or laser therapy (e.g., cataract surgery, laser posterior
                  capsulotomy, etc.) to the study eye within 12 weeks prior to screening;
               3. Eyelid surgery within 4 weeks prior to screening;
               4. History of vitrectomy, glaucoma surgery, macular laser treatment, keratoplasty,
                  or retinal detachment surgery; or
               5. History of treatment with radiotherapy around the study eye including radiation
                  retinopathy
          6. Any concurrent ophthalmic abnormalities that, based on the judgment of the
             investigator, may affect the assessment of safety and therapeutic efficacy or may need
             medical or surgical treatment during the study period (e.g., cloudy ocular media,
             optic neuropathy, amblyopia, etc.).
          7. Hypersensitivity to any of the components of IP or to contrast agents used for FFA and
             ICG angiography.
          8. Pregnant and/or breastfeeding women.
          9. Men and women of childbearing potential who are unwilling to use adequate methods of
             contraception* or who are planning a pregnancy during the study period and for 12
             weeks from the last dose of IP
             -Methods of contraception: hormone contraceptives (oral contraceptives, contraceptive
             patch, etc.), intrauterine device (IUD) (copper IUD, hormonal intrauterine system),
             double barrier method (both male [condom] and female [diaphragm, vaginal sponge, or
             cervical cap]), surgical sterilization (tubal sterilization, vasectomy, etc.)
         10. Having participated in another clinical trial and treated with an IP within 12 weeks
             prior to screening
         11. Distance vision test result of <0.1 for the fellow eye
         12. Other reasons based on which individuals are determined by the investigator to be
             ineligible for study participation.