Study to Assess Safety and Tolerability of PMC-403 in Subjects With Neovascular Age-related Macular Degeneration

NCT05953012 | Completed Phase 1 DMC

• 1 other identifier: PMC403-A01
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 4

Brief Summary

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).

Conditions

Neovascular Age-related Macular Degeneration

Keywords

PMC-403

Outcome Measures

Primary Outcomes (14)

• Maximum tolerated dose (MTD)

  To identify the maximum tolerated dose (MTD), and determine the recommended phase 2 dose (RP2D) of PMC-403 in patients with nAMD. MTD of PMC-403 will be calculated by incidence of DLT at 4 weeks from the first dosing of PMC-403.

  Baseline upto 4 weeks

• Adverse events

  For Treatment-emergent adverse events (TEAEs), Adverse Drug Reactions (ADRs), Serious Adverse Events (SAEs), Serious Adverse Drug Reactions (SADRs), and Adverse Events (AEs) leading to study withdrawal, number of subjects, incidence, number of events, and 95% two-sided confidence interval will be presented by dose group.

  Baseline upto 5 months

• Vital Signs - Pulse Rate (beats/min)

  At each visit, pulse rate will be measured. Vital signs collected will be assessed for change before and after IP dosing and/or change in normal/abnormal findings. By dose group, values at each time point will be presented with number of subjects, mean, standard deviation, median, minimum, and maximum; and change from baseline at each time point will be presented with number of subjects, mean, standard deviation, median, minimum, and maximum.

  Baseline upto 5 months

• Vital Signs - body temperature

  At each visit, body temperature will be measured. Vital signs collected will be assessed for change before and after IP dosing and/or change in normal/abnormal findings. By dose group, values at each time point will be presented with number of subjects, mean, standard deviation, median, minimum, and maximum; and change from baseline at each time point will be presented with number of subjects, mean, standard deviation, median, minimum, and maximum.

  Baseline upto 5 months

• Vital Signs - systolic/diastolic blood pressure (mmHg)

  At each visit, systolic/diastolic blood pressure will be measured. Vital signs collected will be assessed for change before and after IP dosing and/or change in normal/abnormal findings. By dose group, values at each time point will be presented with number of subjects, mean, standard deviation, median, minimum, and maximum; and change from baseline at each time point will be presented with number of subjects, mean, standard deviation, median, minimum, and maximum.

  Baseline upto 5 months

• Laboratory tests - Hematology

  Hematology will be performed at Visits 1, 2, 5, and 7 and at Follow-up Visits 8 and 9 in the SAD groups and at each visit in the MAD groups. The following Hematology parameters will be recorded: white blood cell (WBC), red blood cell (RBC), hemoglobin, hematocrit, platelet, WBC differential count (neutrophil, lymphocyte, monocyte, eosinophil, basophil) Test results collected will be assessed for change before and after IP dosing and/or change in normal/abnormal findings.

  Baseline upto 5 months

• Laboratory tests - Blood chemistry

  Blood chemistry will be performed at Visits 1, 2, 5, and 7 and at Follow-up Visits 8 and 9 in the SAD groups and at each visit in the MAD groups. The following Blood chemistry parameters will be recorded: glucose, aspartate transaminase (AST; SGOT), alanine transaminase (ALT; SGPT), total bilirubin, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total protein, albumin, blood urea nitrogen (BUN), creatinine, uric acid, sodium, potassium, chloride, calcium, phosphorus, C-reactive protein (CRP), HbA1c (to be tested at the screening visit only) Test results collected will be assessed for change before and after IP dosing and/or change in normal/abnormal findings.

  Baseline upto 5 months

• Laboratory tests - Urinalysis

  Urinalysis will be performed at Visits 1, 2, 5, and 7 and at Follow-up Visits 8 and 9 in the SAD groups and at each visit in the MAD groups. For continuous variables, values at each time point will be presented by dose group with number of subjects, mean, standard deviation, median, minimum, and maximum; and change from baseline at each time point will be presented by dose group with number of subjects, mean, standard deviation, median, minimum, and maximum. Additionally, test results collected will be assessed for change before and after IP dosing and/or change in normal/abnormal findings.

  Baseline upto 5 months

• Laboratory tests - Blood coagulation

  Blood coagulation will be performed at Visits 1, 2, 5, and 7 and at Follow-up Visits 8 and 9 in the SAD groups and at each visit in the MAD groups. For continuous variables, values at each time point will be presented by dose group with number of subjects, mean, standard deviation, median, minimum, and maximum; and change from baseline at each time point will be presented by dose group with number of subjects, mean, standard deviation, median, minimum, and maximum. Additionally, test results collected will be assessed for change before and after IP dosing and/or change in normal/abnormal findings.

  Baseline upto 5 months

• Electrocardiogram (ECG)

  Test results will be classified into normal/NCS and CS, and change from baseline at each time point and at the last visit will be presented with frequency and percentage in a shift table by dose group. The following ECG parameters will be recorded: heart rate, RR interval, HR interval, QTc interval and QRS interval.

  Baseline upto 5 months

• Ophthalmologic examination - Slit lamp examination

  Slit lamp examination measuring will be performed according to Schedule of Events. For continuous variables, values at each time point will be presented by dose group with number of subjects, mean, standard deviation, median, minimum, and maximum. The ophthalmologic examination results will be assessed for change in normal/abnormal status before and after IP dosing.

  Baseline upto 5 months

• Ophthalmologic examination - fundus examination

  fundus examination measuring will be performed according to Schedule of Events. For continuous variables, values at each time point will be presented by dose group with number of subjects, mean, standard deviation, median, minimum, and maximum. The ophthalmologic examination results will be assessed for change in normal/abnormal status before and after IP dosing.

  Baseline upto 5 months

• Ophthalmologic examination - spectral domain-optical coherence tomography (SD-OCT)

  SD-OCT will be performed according to Schedule of Events. For continuous variables, values at each time point will be presented by dose group with number of subjects, mean, standard deviation, median, minimum, and maximum. The ophthalmologic examination results will be assessed for change in normal/abnormal status before and after IP dosing.

  Baseline upto 5 months

• Ophthalmologic examination - intraocular pressure (IOP)

  IOP will be performed according to Schedule of Events. During the study visits involving IP dosing (SAD: Visits 2, MAD: Visits 2, 5, 7), IOP will be measured a total of 3 times (once before dosing and twice after dosing). For continuous variables, values at each time point will be presented by dose group with number of subjects, mean, standard deviation, median, minimum, and maximum. The ophthalmologic examination results will be assessed for change in normal/abnormal status before and after IP dosing.

  Baseline upto 5 months

Secondary Outcomes (7)

• Change in best corrected visual acuity (BCVA)

  Baseline upto 5 months

• Change in central retinal thickness (CRT)

  Baseline upto 5 months

• Presence of intraretinal fluid (IRF)

  Baseline upto 5 months

• Presence of subretinal fluid (SRF)

  Baseline upto 5 months

• Presence of sub-RPE fluid

  Baseline upto 5 months

Other Outcomes (8)

• Pharmacokinetic parameters - Area under the blood concentration-time curve (AUC)

  Baseline upto 5 months

• Pharmacokinetic parameters - Maximum blood concentration (Cmax)

  Baseline upto 5 months

• Pharmacokinetic parameters - Minimum blood concentration (Cmin)

  Baseline upto 5 months

Study Arms (2)

PART 1- SAD

EXPERIMENTAL

The SAD part of the study will be conducted in a step-wise manner for a total of 4 dose levels of PMC-403. * Dose level 1: 0.7 mg/eye, baseline(Day 0) * Dose level 2: 2 mg/eye, baseline(Day 0) * Dose level 3: 3 mg/eye, baseline(Day 0) * Dose level 4: 4 mg/eye, baseline(Day 0)

Drug: PMC-403

PART 2- MAD

EXPERIMENTAL

Upon the end of the SAD part of the study, the MAD part is planned to be conducted in a step-wise manner for a total of 2 dose levels. * Dose level 1: 3 mg/eye, baseline(Day 0), Week 4(Day 28), Week 8(Day 56) * Dose level 2: 4 mg/eye, baseline(Day 0), Week 4(Day 28), Week 8(Day 56)

Drug: PMC-403

Interventions

PMC-403 DRUG

PMC-403 will be administered Intravitreal.

Also known as: Monotherapy

PART 1- SAD; PART 2- MAD

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \* 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:
• The eye with lower (severer) best corrected visual acuity (BCVA) at baseline will be selected as the study eye.
• If both eyes have the same BCVA, the right eye will be selected as the study.
• Male and female ≥50 years of age at the time of written informed consent.
• 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
• \>12 weeks must have elapsed since the last dose of anti-VEGF IVT at the time of screening.
• 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.
• 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.
• 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).
• Voluntary written informed consent to study participation.

You may not qualify if:

• At the screening visit:
• Uncontrolled ocular hypertension (≥ 25 mmHg) despite drug therapy;
• Retinal pigment epithelium (RPE) tears involving the macula;
• Improvement in visual acuity is not expected due to scars, fibrosis, or atrophy involving the fovea;
• Presence of vitreous hemorrhage;
• Aphakia or absence of posterior capsule (with the exception of pseudophakic eyes treated with laser posterior capsulotomy);
• Presence of any causes of CNV other than nAMD, such as ocular histoplasmosis, trauma, pathological myopia, angioid streak, choroidal rupture, or uveitis; or
• 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.).
• Any of the following conditions or medical history in either eye:
• Current or known history of at least moderate diabetic retinopathy or diabetic macular edema;
• Active intraocular or periocular infections or inflammations (e.g., infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, etc.); or
• History of idiopathic or autoimmune uveitis.
• Any of the following systemic diseases:
• 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;
• Uncontrolled hypertension with systolic or diastolic blood pressure \> 160/100 mmHg;

Sponsors & Collaborators

• PharmAbcine: lead
• C&R Research, Inc.: collaborator

Study Sites (4)

Seoul National University Bundang Hospital

Seoul, Bundang-gu, 13620, South Korea

Location

Yeungnam University

Daegu, Nam-gu, 42415, South Korea

Location

Yonsei University Health System

Seoul, Seodaemun-gu, 03722, South Korea

Location

ASAN Medical Center

Seoul, Songpa-gu, 05505, South Korea

Location

Study Officials

• SeJoon Woo

  Seoul National University Bundang Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2023
• First Posted: July 19, 2023
• Study Start: July 20, 2023
• Primary Completion: August 22, 2025
• Study Completion: December 17, 2025
• Last Updated: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

KR (4)