First-In-Human Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Escalating Single And Multiple Doses Of CSL040 In Healthy Subjects
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
62
Nucleus Network Pty Ltd
Herston, Queensland, Australia
Number of participants with treatment emergent adverse events (TEAEs), adverse events of special interests (AESIs), and serious adverse events (SAEs)
Time frame: Part A (SAD): Up to 105 days; Part B (MAD): Up to 174 days
Percentages of participants with TEAEs, AESIs, and SAEs
Time frame: Part A (SAD): Up to 105 days; Part B (MAD): Up to 174 days
The Number of Clinically Significant Changes from Baseline in Clinical Laboratory Tests Reported as AE
Clinical laboratory tests include hematology, biochemistry, coagulation, and urinalysis collected during the study. The investigator determines if the changes in laboratory test results are clinically significant.
Time frame: Baseline and up to 69 days
Number of participants with vital signs out of normal range
Blood pressure (systolic and diastolic), pulse rate, respiratory rate and tympanic temperature will be assessed.
Time frame: Baseline and up to 69 days
Change from Baseline in corrected QT interval using Fridericia's formula (QTcF) values of triplicate electrocardiograms
Time frame: Baseline and up to 69 days
Absolute values of QTcF on electrocardiograms
Time frame: Baseline and up to 69 days
Number of participants with abnormal electrocardiogram findings
Time frame: Baseline and up to 69 days
Part A (SAD): Maximum concentration (Cmax)
Time frame: Up to 56 days
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Part A (SAD): Time to reach maximum concentration (Tmax)
Time frame: Up to 56 days
Part A (SAD): Time to Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last)
Time frame: Up to 56 days
Part A (SAD): Area under the concentration-time curve from time 0 to infinity (AUC0-infinity)
Time frame: Up to 56 days
Part A (SAD): Total systemic clearance (CL)
Time frame: Up to 56 days
Part A (SAD): Volume of distribution (V)
Time frame: Up to 56 days
Part A (SAD): Terminal elimination half-life (T1/2)
Time frame: Up to 56 days
Part B (MAD): Maximum concentration (Cmax)
Time frame: Up to 69 days
Part B (MAD): Time to reach maximum concentration (Tmax)
Time frame: Up to 69 days
Part B (MAD): Time to Area under the concentration-time curve in 1 dosing interval (AUCtau)
Time frame: Up to 69 days
Part B (MAD): Accumulation index (accumulation ratio determined by the ratio of steady state AUCtau to single dose AUCtau)
Time frame: Up to 69 days
Part B (MAD): Lowest concentration prior to dosing (Ctrough)
Time frame: Up to 69 days
Part B (MAD): Total systemic clearance (CL)
Time frame: Up to 69 days
Part B (MAD): Volume of distribution at steady state (Vss)
Time frame: Up to 69 days
Part A (SAD) and Part B (MAD): Percent change from Baseline in pharmacodynamic (PD) parameters
Levels of Wieslab ex vivo pathway activity for classical, lectin and alternative complement pathways, CH50 (hemolysis of sheep erythrocytes) and ApH50 (hemolysis of rabbit erythrocytes) will be measured and for each PD parameter presented as percent change from baseline over time profiles.
Time frame: Up to 56 days (Part A) and up to 69 days (Part B)
Part A (SAD) and Part B (MAD): Maximum percent change from Baseline (Emax) in PD parameters
Levels of Wieslab ex vivo pathway activity for classical, lectin and alternative complement pathways, CH50 and ApH50 will be measured and for each PD parameter the maximum percent change from Baseline (Emax) will be determined.
Time frame: Up to 56 days (Part A) and up to 69 days (Part B)
Part A (SAD) and Part B (MAD): Time to maximum percent change from Baseline (TEmax) in PD parameters
Levels of Wieslab ex vivo pathway activity for classical, lectin and alternative complement pathways, CH50 and ApH50 will be measured and for each PD parameter the Time to maximum percent change from Baseline (TEmax) will be determined.
Time frame: Up to 56 days (Part A) and up to 69 days (Part B)
Part A (SAD) and Part B (MAD): Time below Baseline in PD parameters
Levels of Wieslab ex vivo pathway activity for classical, lectin and alternative complement pathways, CH50 and ApH50 will be measured and for each PD parameter the Time below Baseline will be determined.
Time frame: Up to 56 days (Part A) and up to 69 days (Part B)
Part A (SAD) and Part B (MAD): AUC below Baseline in PD parameters
Levels of Wieslab ex vivo pathway activity for classical, lectin and alternative complement pathways, CH50 and ApH50 will be measured and for each PD parameter the AUC below Baseline will be determined.
Time frame: Up to 56 days (Part A) and up to 69 days (Part B)
Part A (SAD) and Part B (MAD): Number of serum samples with Positive antidrug antibodies (ADAs) binding to CSL040
Time frame: Up to 56 days (Part A) and up to 69 days (Part B)
Part A (SAD) and Part B (MAD): Number of participants with presence of treatment-emergent ADAs
Time frame: Up to 56 days (Part A) and up to 69 days (Part B)