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).
In this study, Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) will be carried out in a sequential manner. \- PART 1- SAD The SAD part of the study will be conducted in a step-wise manner for a total of 4 dose levels (0.7 mg, 2 mg, 3 mg, 4 mg). To each dose group, 3 subjects at minimum or 6 subjects at maximum will be recruited. In the SAD part, dose escalation will be performed up to 4 mg/eye (50 uL/eye) until the MTD is identified. In the SAD part, a maximum of 24 participants are to be enrolled. \- PART 2- MAD 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 (3 mg, 4 mg). In the MAD part will begin with dose level 1 (3 mg). Subjects will be given a total of 3 doses of IP at 4-week intervals over a total period of 12 weeks and will be assessed for safety and tolerability according to study procedures. While a total of 6 subjects are to be recruited per dose group in the MAD part. Dose escalation will be performed up to 4 mg/eye (50 uL/eye) until the MTD is identified. In the MAD part, a maximum of 12 participants are to be enrolled.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
17
PMC-403 will be administered Intravitreal.
Seoul National University Bundang Hospital
Seoul, Bundang-gu, South Korea
Yeungnam University
Daegu, Nam-gu, South Korea
Yonsei University Health System
Seoul, Seodaemun-gu, South Korea
ASAN Medical Center
Seoul, Songpa-gu, South Korea
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline upto 5 months
Change in best corrected visual acuity (BCVA)
It is measured by early treatment of diabetic retinopathy study (ETDRS) chart at each point of visit. For BCVA 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.
Time frame: Baseline upto 5 months
Change in central retinal thickness (CRT)
It is measured by SD-OCT at each point of visit. For CRT 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.
Time frame: Baseline upto 5 months
Presence of intraretinal fluid (IRF)
It is measured by SD-OCT at each point of visit. For presence of IRF frequency, percentage, and 95% confidence interval will be presented by dose group.
Time frame: Baseline upto 5 months
Presence of subretinal fluid (SRF)
It is measured by SD-OCT at each point of visit. For presence of SRF frequency, percentage, and 95% confidence interval will be presented by dose group.
Time frame: Baseline upto 5 months
Presence of sub-RPE fluid
It is measured by SD-OCT at each point of visit. For presence of sub-RPE fluid frequency, percentage, and 95% confidence interval will be presented by dose group.
Time frame: Baseline upto 5 months
Change from baseline in choroidal neovascularization (CNV) lesion size as measured by Fundus Fluorescein Angiography (FFA)
FFA will be performed to measure the size of CNV lesions and to assess vascular leakage. For CNV lesion size 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.
Time frame: Baseline upto 5 months
Change from baseline in CNV lesion size as measured by ICG angiography
ICG angiography will be performed to measure the size of CNV lesions and to assess vascular leakage. For CNV lesion size 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.
Time frame: Baseline upto 5 months