This is a Phase 1A, first in human, randomized, double-blinded, placebo-controlled, dose escalation study of PMG1015 in healthy adult volunteers. PMG1015 is a monoclonal antibody, being developed as a novel therapeutic treatment for patients with Idiopathic Pulmonary fibrosis (IPF). This study aims to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of PMG1015 after Single ascending doses (SAD).
Participants will be enrolled and randomized into 1 of 7 cohorts in a double-blind manner.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
54
Dose level 1 of PMG1015
Dose level 2 of PMG1015
Dose level 3 of PMG1015
Q-Pharm Pty Ltd, Clive Berghofer Cancer Research Centre
Herston, Queensland, Australia
The incidence of Treatment-emergent adverse events (TEAEs)
An Adverse Event (AE) is any event, side-effect or any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs are AEs that occur following the start of treatment.
Time frame: Day 1-Day 85
The severity of Treatment-emergent adverse events (TEAEs)
TEAEs are AEs that occur following the start of treatment.
Time frame: Day 1-Day 85
The incidence of Serious adverse events (SAEs)
A serious adverse event (SAE) is defined as an AE occurring during any study phase and at any dose of IP (active or placebo) that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect.
Time frame: Day 1-Day 85
The severity of Serious adverse events (SAEs)
A serious adverse event (SAE) is defined as an AE occurring during any study phase and at any dose of IP (active or placebo) that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect.
Time frame: Day 1- Day 85
Number of participants with abnormally clinical vital signs
Vital signs include pulse rate (PR), blood pressure (BP), respiratory rate (RR) and tympanic temperature (T)
Time frame: Day 1- Day 85
Number of participants with abnormal clinically significant 12-lead electrocardiogram (ECG) parameters
All ECG tracings will be reviewed by the PI or designee and assessed for clinical significance.
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Dose level 4 of PMG1015
Dose level 5 of PMG1015
Dose level 6 of PMG1015
Placebo to match
Dose level 7 of PMG1015
Time frame: Day 1-Day 85.
Number of participants with abnormal clinically significant clinical laboratory results
Clinical laboratory test include hematology, coagulation, biochemistry, and urinalysis.
Time frame: Day 1- Day 85
MTD of PMG1015 in healthy participants
Maximum tolerated dose of PMG1015 in healthy participants
Time frame: Day 1- Day 85
Number of patients with abnormal clinically significant results from physical examination
Complete physical examination include, general appearance, head, eyes, ears, nose, throat, dentition, thyroid, chest (heart, lungs), abdomen, skin, neurological, extremities, back, neck, musculoskeletal, and lymph nodes.
Time frame: Day 1-Day 85
Area under the serum-concentration time curve (AUC) from time zero (from the start of infusion time) to the last time point with measurable analyte concentration (AUC0-t)
Area under the plasma concentration versus time curve (AUC) from time 0 to time of last quantifiable concentration
Time frame: Day 1-Day 85.
AUC from time zero to infinity (AUC0-∞)
Area under the plasma concentration versus time curve (AUC) from time 0 (from the start of infusion) extrapolated to infinity
Time frame: Day 1-Day 85.
To determine %AUCexp
The percentage of the AUC that has been extrapolated beyond the last observed data point
Time frame: Day 1-Day 85.
To determine Cmax
Maximum observed serum PMG1015 concentration
Time frame: Day 1-Day 85.
To determine Tmax, derived from serum concentration of each dose of PMG1015
Time to maximum observed concentration
Time frame: Day 1-Day 85.
To determine t1/2
Terminal elimination half life summarized by dosing regimen
Time frame: Day 1-Day 85.
Apparent total body clearance (CL)
CL is the measure of the rate at which a drug is metabolized or eliminated by normal biological processes
Time frame: Day 1-Day 85.
Apparent volume of distribution during the terminal phase (Vz)
Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time frame: Day 1-Day 85.
Apparent terminal elimination rate constant (λz or kel)
λz is calculated using log-linear regression of the terminal portions of the plasma concentrations versus time curves.
Time frame: Day 1-Day 85.
Levels of ADA
Anti-drug antibody levels in blood
Time frame: Day 1-Day 85