Acute Myocardial Infarction
Conditions
Brief summary
This is a multicenter randomized, double-blind, placebo-controlled, parallel-group, dose-ranging phase 2b study to investigate the hepatic and renal safety and tolerability of multiple dose administration of two dose levels of CSL112 compared with placebo in subjects with acute myocardial infarction (AMI).
Interventions
BIOLOGICALCSL112
CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
BIOLOGICALPlacebo
0.9% weight/volume sodium chloride solution (ie, normal saline)
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women, at least 18 years of age, with evidence of myocardial necrosis in a clinical setting consistent with a type I (spontaneous) acute myocardial infarction (AMI), in the last week.
Exclusion criteria
* Ongoing hemodynamic instability * Evidence of hepatobiliary disease * Evidence of chronic kidney disease (CKD) (Stage III, IV, or V), defined as moderate or severe renal impairment or if subject is receiving dialysis * Evidence of unstable renal function * History of acute kidney injury after previous exposure to an intravenous contrast agent. * Known history of allergies, hypersensitivity or deficiencies to CSL112 or any of its components * Other severe comorbid condition, concurrent medication, or other issue that renders the subject unsuitable for participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With Clinically Important Change in Drug-induced Liver Injury | From baseline (before first infusion) to Day 29. | A clinically important change in drug-induced liver injury is defined as a change (from baseline) in alanine aminotransferase (ALT) greater than 3 times the upper limit of normal (ULN) or a change in total bilirubin greater than 2 times ULN, that is confirmed upon repeat measurement. |
| Percent of Participants With Clinically Important Change in Renal Status | From baseline (before first infusion) to Day 29. | A clinically important change in renal status is defined as a serum creatinine (Cr) increase to ≥ 1.5 x the baseline value that is confirmed upon repeat measurement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Concentrations of Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) at End of First Infusion for All Participants | Before first infusion and end of first infusion | Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) are analytes of CSL112 |
| Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for All Participants | Before first infusion and end of fourth infusion | — |
| Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Normal Renal Function | Before first infusion and end of first infusion | apoA-I and PC are analytes of CSL112 |
| Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Normal Renal Function | Before first infusion and end of fourth infusion | apoA-I and PC are analytes of CSL112 |
| Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Mild Renal Impairment | Before first infusion and end of first infusion | apoA-I and PC are analytes of CSL112 |
| Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Mild Renal Impairment | Before first infusion and end of fourth infusion | apoA-I and PC are analytes of CSL112 |
| Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for All Participants | Before first infusion (baseline) and for up to approximately 7 days after first infusion | Cmax is the maximal plasma concentration. |
| Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for All Participants | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | Cmax is the maximal plasma concentration. |
| Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function | Before first infusion (baseline) and for up to approximately 7 days after first infusion | Cmax is the maximal plasma concentration. |
| Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | Before first infusion (baseline) and for up to approximately 7 days after first infusion | Cmax is the maximal plasma concentration. |
| Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | Cmax is the maximal plasma concentration. |
| Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for All Participants | Before and for 7 days after the first infusion | Tmax is time to maximal plasma concentration |
| Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for All Participants | Before and for 7 days after the fourth infusion | Tmax is time to maximal plasma concentration |
| Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function | Before and for 7 days after the first infusion | Tmax is time to maximal plasma concentration |
| Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | Before and for 7 days after the fourth infusion | Tmax is time to maximal plasma concentration |
| Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | Before and for 7 days after the first infusion | Tmax is time to maximal plasma concentration |
| Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | Before and for 7 days after the fourth infusion | Tmax is time to maximal plasma concentration |
| Change From Baseline in Plasma Area Under the Curve (AUC) AUC0 - Last for apoA-I and PC After First Infusion for All Participants | Before first infusion (baseline) and for up to approximately 7 days after first infusion | Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\] |
| Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for All Participants | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\] |
| Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Participants With Normal Renal Function | Before first infusion (baseline) and for up to approximately 7 days after first infusion | Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\] |
| Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\] |
| Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Subjects With Mild Renal Impairment | Before first infusion (baseline) and for up to approximately 7 days after first infusion | Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\] |
| Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\] |
| Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | Before first infusion (baseline) and for up to approximately 7 days after first infusion | AUC from baseline to time point t (AUC0-t) |
| Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | AUC from baseline to time point t (AUC0-t) |
| Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | Before first infusion (baseline) and for up to approximately 7 days after first infusion | AUC from baseline to time point t (AUC0-t) |
| Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | AUC from baseline to time point t (AUC0-t) |
| Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | Before first infusion (baseline) and for up to approximately 7 days after first infusion | AUC from baseline to time point t (AUC0-t) |
| Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | AUC from baseline to time point t (AUC0-t) |
| Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for All Participants | Before first infusion (baseline) and for up to approximately 7 days after first infusion | AUC0-∞ is plasma area under the curve (AUC0-infinity) |
| Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for All Participants | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | AUC0-∞ is plasma area under the curve (AUC0-infinity) |
| Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Normal Renal Function | Before first infusion (baseline) and for up to approximately 7 days after first infusion | AUC0-∞ is plasma area under the curve (AUC0-infinity) |
| Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | AUC0-∞ is plasma area under the curve (AUC0-infinity) |
| Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | Before first infusion (baseline) and for up to approximately 7 days after first infusion | AUC0-∞ is plasma area under the curve (AUC0-infinity) |
| Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | AUC0-∞ is plasma area under the curve (AUC0-infinity) |
| Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for All Participants | Before first infusion (baseline) and for up to approximately 7 days after first infusion | — |
| Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for All Participants | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | — |
| Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Normal Renal Function | Before first infusion (baseline) and for up to approximately 7 days after first infusion | — |
| Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | — |
| Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | Before first infusion (baseline) and for up to approximately 7 days after first infusion | — |
| Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | — |
| Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for All Participants | Before first infusion (baseline) and for up to approximately 7 days after first infusion | — |
| Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for All Participants | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | — |
| Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Normal Renal Function | Before first infusion (baseline) and for up to approximately 7 days after first infusion | — |
| Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | — |
| Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | Before first infusion (baseline) and for up to approximately 7 days after first infusion | — |
| Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | — |
| Change From Baseline in Plasma Volume of Distribution at Steady State (Vss) for apoA-I and PC After First Infusion for All Participants | Before first infusion (baseline) and for up to approximately 7 days after first infusion | — |
| Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for All Participants | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | — |
| Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Normal Renal Function | Before first infusion (baseline) and for up to approximately 7 days after first infusion | — |
| Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | — |
| Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | Before first infusion (baseline) and for up to approximately 7 days after first infusion | — |
| Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | — |
| The Percentage of Participants With a Time-to-first Major Adverse Cardiovascular Event (MACE) | From the start of the first infusion up to approximately 382 days | The MACE is a 4-component composite comprised of the time to the first of the following events: CV death, nonfatal myocardial infarction, ischemic stroke (non-hemorrhagic), and hospitalization for unstable angina. |
| Percent of Participants With Any Adverse Event (AE) | From the start of first infusion, up to approximately Day 382 | — |
| Percent of Participants Who Experience Bleeding Events | From the start of first infusion, up to approximately Day 112 | The number of subjects who experience bleeding events as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al, 2011) |
| Change From Baseline in Serum Antibodies to CSL112 and apoA-I | Before first infusion, up to approximately Day 112 | — |
| Number of Participants With Positive Serology Results for IgG and IgM Antibodies to Parvovirus B19 | Study Day 112 | — |
| Number of Participants With Parvovirus B19 DNA in Serum | Study Day 112 | — |
| Percent of Participants With the Occurrence of Suspected Adverse Drug Reactions | From the start of first infusion, up to approximately Day 382 | The overall percentage of subjects: * with adverse events (AEs), including local tolerability events, that begin during or within 1 hour of an infusion; or * with AEs considered to be causally related to the test product; or * who experience an AE for which the incidence rate in an active treatment arm exceeds the exposure-adjusted incidence rate in the placebo arm by 30% or more, provided the difference in incidence rates is 1% or more. |
| Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | Before first infusion (baseline) and for up to approximately 7 days after fourth infusion | Cmax is the maximal plasma concentration. |
Countries
Australia, Austria, Bulgaria, Canada, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Safety Lead-in [CSL112 (2 g)] In the safety lead-in, a small number of subjects (evenly stratified between subjects with normal renal function or mild renal impairment) were administered a single, 2 g infusion of CSL112. | 9 |
| CSL112 (2 g) CSL112 (2 g) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks.
CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles. | 419 |
| CSL112 (6 g) CSL112 (6 g) is to be administered as an IV infusion once weekly for 4 consecutive weeks.
CSL112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles. | 421 |
| Placebo Placebo is to be administered as an IV infusion at the same frequency, volume and duration as either the low dose or high dose CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline) | 418 |
| Total | 1,267 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 11 | 6 | 12 |
| Overall Study | Death | 0 | 2 | 2 | 1 |
| Overall Study | Distance to center | 0 | 1 | 1 | 0 |
| Overall Study | Due to key hepatic values | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Overall Study | Missed IV due to pharmacy error | 0 | 0 | 1 | 0 |
| Overall Study | Non-compliance | 0 | 2 | 1 | 1 |
| Overall Study | Patient decision | 0 | 7 | 9 | 14 |
| Overall Study | Patient did not want another infusion | 0 | 3 | 3 | 2 |
| Overall Study | Patient unable to come to site/attend visit | 0 | 6 | 11 | 6 |
| Overall Study | Physician Decision | 0 | 0 | 2 | 0 |
| Overall Study | Randomized by error/screen failure | 0 | 0 | 1 | 0 |
| Overall Study | Unable to contact patient | 0 | 3 | 1 | 2 |
| Overall Study | Vacation | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 7 | 3 | 4 |
Baseline characteristics
| Characteristic | Safety Lead-in [CSL112 (2 g)] | CSL112 (2 g) | CSL112 (6 g) | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 113 Participants | 125 Participants | 117 Participants | 357 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 306 Participants | 296 Participants | 301 Participants | 910 Participants |
| Age, Continuous | 59.0 years STANDARD_DEVIATION 7.19 | 57.7 years STANDARD_DEVIATION 10.15 | 59.2 years STANDARD_DEVIATION 9.87 | 58.1 years STANDARD_DEVIATION 10.57 | 58.3 years STANDARD_DEVIATION 10.21 |
| Region of Enrollment Australia | 0 participants | 6 participants | 6 participants | 6 participants | 18 participants |
| Region of Enrollment Austria | 0 participants | 2 participants | 3 participants | 2 participants | 7 participants |
| Region of Enrollment Bulgaria | 0 participants | 47 participants | 47 participants | 46 participants | 140 participants |
| Region of Enrollment Canada | 0 participants | 9 participants | 9 participants | 7 participants | 25 participants |
| Region of Enrollment Czechia | 0 participants | 33 participants | 35 participants | 36 participants | 104 participants |
| Region of Enrollment Denmark | 0 participants | 8 participants | 10 participants | 10 participants | 28 participants |
| Region of Enrollment France | 0 participants | 0 participants | 2 participants | 1 participants | 3 participants |
| Region of Enrollment Germany | 0 participants | 28 participants | 30 participants | 28 participants | 86 participants |
| Region of Enrollment Hungary | 9 participants | 66 participants | 67 participants | 69 participants | 211 participants |
| Region of Enrollment Israel | 0 participants | 27 participants | 27 participants | 27 participants | 81 participants |
| Region of Enrollment Italy | 0 participants | 7 participants | 7 participants | 8 participants | 22 participants |
| Region of Enrollment Netherlands | 0 participants | 48 participants | 48 participants | 49 participants | 145 participants |
| Region of Enrollment Poland | 0 participants | 70 participants | 69 participants | 65 participants | 204 participants |
| Region of Enrollment Spain | 0 participants | 6 participants | 5 participants | 6 participants | 17 participants |
| Region of Enrollment United Kingdom | 0 participants | 3 participants | 2 participants | 4 participants | 9 participants |
| Region of Enrollment United States | 0 participants | 59 participants | 54 participants | 54 participants | 167 participants |
| Renal function from Interactive Web Response System (IWRS) Mild renal impairment | 5 participants | 224 participants | 229 participants | 227 participants | 685 participants |
| Renal function from Interactive Web Response System (IWRS) Normal renal function | 4 participants | 195 participants | 192 participants | 191 participants | 582 participants |
| Sex: Female, Male Female | 2 Participants | 82 Participants | 98 Participants | 77 Participants | 259 Participants |
| Sex: Female, Male Male | 7 Participants | 337 Participants | 323 Participants | 341 Participants | 1008 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 9 | 5 / 415 | 4 / 416 | 1 / 413 |
| other Total, other adverse events | 2 / 9 | 15 / 415 | 23 / 416 | 9 / 413 |
| serious Total, serious adverse events | 1 / 9 | 66 / 415 | 54 / 416 | 55 / 413 |
Outcome results
Primary
Percent of Participants With Clinically Important Change in Drug-induced Liver Injury
A clinically important change in drug-induced liver injury is defined as a change (from baseline) in alanine aminotransferase (ALT) greater than 3 times the upper limit of normal (ULN) or a change in total bilirubin greater than 2 times ULN, that is confirmed upon repeat measurement.
Time frame: From baseline (before first infusion) to Day 29.
Population: The Safety population (SP) comprised all subjects who were randomized into the main study or PK/PD substudy and received at least a partial infusion of the investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL112 (2 g) | Percent of Participants With Clinically Important Change in Drug-induced Liver Injury | 1.0 percentage of participants |
| CSL112 (6 g) | Percent of Participants With Clinically Important Change in Drug-induced Liver Injury | 0.5 percentage of participants |
| Placebo | Percent of Participants With Clinically Important Change in Drug-induced Liver Injury | 0 percentage of participants |
p-value: =0.124195% CI: [-0.1, 2.5]Newcombe-Wilson score method
p-value: =0.499495% CI: [-0.5, 1.7]Newcombe-Wilson score method
Primary
Percent of Participants With Clinically Important Change in Renal Status
A clinically important change in renal status is defined as a serum creatinine (Cr) increase to ≥ 1.5 x the baseline value that is confirmed upon repeat measurement.
Time frame: From baseline (before first infusion) to Day 29.
Population: SP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL112 (2 g) | Percent of Participants With Clinically Important Change in Renal Status | 0 percentage of participants |
| CSL112 (6 g) | Percent of Participants With Clinically Important Change in Renal Status | 0.7 percentage of participants |
| Placebo | Percent of Participants With Clinically Important Change in Renal Status | 0.2 percentage of participants |
p-value: =0.498895% CI: [-1.4, 0.7]Newcombe-Wilson score method
p-value: =0.624195% CI: [-0.7, 1.9]Newcombe-Wilson score method
Secondary
Change From Baseline in Concentrations of Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) at End of First Infusion for All Participants
Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) are analytes of CSL112
Time frame: Before first infusion and end of first infusion
Population: The pharmacokinetic population (PK) comprised all subjects who received at least 1 infusion of investigational product and had at least 1 post baseline measurable plasma concentration of apoA-I or PC.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Concentrations of Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) at End of First Infusion for All Participants | apoA-I | 35.9 mg/dL | Standard Deviation 22.13 |
| CSL112 (2 g) | Change From Baseline in Concentrations of Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) at End of First Infusion for All Participants | PC | 57.7 mg/dL | Standard Deviation 31.12 |
| CSL112 (6 g) | Change From Baseline in Concentrations of Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) at End of First Infusion for All Participants | apoA-I | 136.1 mg/dL | Standard Deviation 54.37 |
| CSL112 (6 g) | Change From Baseline in Concentrations of Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) at End of First Infusion for All Participants | PC | 180.4 mg/dL | Standard Deviation 74.4 |
| Placebo | Change From Baseline in Concentrations of Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) at End of First Infusion for All Participants | apoA-I | -4.7 mg/dL | Standard Deviation 13.46 |
| Placebo | Change From Baseline in Concentrations of Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) at End of First Infusion for All Participants | PC | -1.2 mg/dL | Standard Deviation 20.43 |
Secondary
Change From Baseline in Plasma Area Under the Curve (AUC) AUC0 - Last for apoA-I and PC After First Infusion for All Participants
Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\]
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Area Under the Curve (AUC) AUC0 - Last for apoA-I and PC After First Infusion for All Participants | apoA-I | 1703 mg•h/dL | Standard Deviation 2149 |
| CSL112 (2 g) | Change From Baseline in Plasma Area Under the Curve (AUC) AUC0 - Last for apoA-I and PC After First Infusion for All Participants | PC | -66.12 mg•h/dL | Standard Deviation 3653 |
| CSL112 (6 g) | Change From Baseline in Plasma Area Under the Curve (AUC) AUC0 - Last for apoA-I and PC After First Infusion for All Participants | apoA-I | 4819 mg•h/dL | Standard Deviation 2580 |
| CSL112 (6 g) | Change From Baseline in Plasma Area Under the Curve (AUC) AUC0 - Last for apoA-I and PC After First Infusion for All Participants | PC | 869 mg•h/dL | Standard Deviation 3796 |
| Placebo | Change From Baseline in Plasma Area Under the Curve (AUC) AUC0 - Last for apoA-I and PC After First Infusion for All Participants | apoA-I | -766 mg•h/dL | Standard Deviation 2248 |
| Placebo | Change From Baseline in Plasma Area Under the Curve (AUC) AUC0 - Last for apoA-I and PC After First Infusion for All Participants | PC | -2096 mg•h/dL | Standard Deviation 3372 |
Secondary
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for All Participants
AUC0-∞ is plasma area under the curve (AUC0-infinity)
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for All Participants | apoA-I | 1425 mg•h/dL | Standard Deviation 1297 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for All Participants | PC | 1850 mg•h/dL | Standard Deviation 3120 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for All Participants | apoA-I | 6090 mg•h/dL | Standard Deviation 3642 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for All Participants | PC | 1678 mg•h/dL | Standard Deviation 651 |
| Placebo | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for All Participants | PC | 6979 mg•h/dL | Standard Deviation 0 |
Secondary
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment
AUC0-∞ is plasma area under the curve (AUC0-infinity)
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I | 1842 mg•h/dL | Standard Deviation 1451 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC | 3210 mg•h/dL | Standard Deviation 4052 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I | 8032 mg•h/dL | Standard Deviation 4220 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC | 1761 mg•h/dL | Standard Deviation 566 |
| Placebo | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC | 6979 mg•h/dL | Standard Deviation 0 |
Secondary
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Normal Renal Function
AUC0-∞ is plasma area under the curve (AUC0-infinity)
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I | 589 mg•h/dL | Standard Deviation 17 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC | 490 mg•h/dL | Standard Deviation 1540 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I | 4505 mg•h/dL | Standard Deviation 2528 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC | 1596 mg•h/dL | Standard Deviation 785 |
Secondary
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for All Participants
AUC0-∞ is plasma area under the curve (AUC0-infinity)
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 15540 mg•h/dL | Standard Deviation 19437 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for All Participants | PC | 2015 mg•h/dL | Standard Deviation 2855 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 13570 mg•h/dL | Standard Deviation 6965 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for All Participants | PC | 12863 mg•h/dL | Standard Deviation 16731 |
| Placebo | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 4615 mg•h/dL | Standard Deviation 0 |
Secondary
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment
AUC0-∞ is plasma area under the curve (AUC0-infinity)
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 11951 mg•h/dL | Standard Deviation 7374 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC | 4769 mg•h/dL | Standard Deviation 4128 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 13157 mg•h/dL | Standard Deviation 6734 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC | 12827 mg•h/dL | Standard Deviation 18453 |
Secondary
Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function
AUC0-∞ is plasma area under the curve (AUC0-infinity)
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 17079 mg•h/dL | Standard Deviation 23224 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC | 638 mg•h/dL | Standard Deviation 566 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 12422 mg•h/dL | Standard Deviation 7399 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC | 16142 mg•h/dL | Standard Deviation 17777 |
| Placebo | Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 4615 mg•h/dL | Standard Deviation 0 |
Secondary
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Participants With Normal Renal Function
Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\]
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I | 1278 mg•h/dL | Standard Deviation 1742 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC | -1382 mg•h/dL | Standard Deviation 2853 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I | 3762 mg•h/dL | Standard Deviation 2367 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC | -137 mg•h/dL | Standard Deviation 4057 |
| Placebo | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I | -516 mg•h/dL | Standard Deviation 2091 |
| Placebo | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC | -1337 mg•h/dL | Standard Deviation 2590 |
Secondary
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Subjects With Mild Renal Impairment
Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\]
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Subjects With Mild Renal Impairment | apoA-I | 2205 mg•h/dL | Standard Deviation 2543 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Subjects With Mild Renal Impairment | PC | 1489 mg•h/dL | Standard Deviation 4003 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Subjects With Mild Renal Impairment | apoA-I | 5917 mg•h/dL | Standard Deviation 2568 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Subjects With Mild Renal Impairment | PC | 1828 mg•h/dL | Standard Deviation 3661 |
| Placebo | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Subjects With Mild Renal Impairment | apoA-I | -1416 mg•h/dL | Standard Deviation 2763 |
| Placebo | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Subjects With Mild Renal Impairment | PC | -4068 mg•h/dL | Standard Deviation 4634 |
Secondary
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for All Participants
Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\]
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 4579 mg•h/dL | Standard Deviation 2705 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for All Participants | PC | 70.7 mg•h/dL | Standard Deviation 5327 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 8985 mg•h/dL | Standard Deviation 4263 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for All Participants | PC | 2499 mg•h/dL | Standard Deviation 7662 |
| Placebo | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 747 mg•h/dL | Standard Deviation 3226 |
| Placebo | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for All Participants | PC | -2185 mg•h/dL | Standard Deviation 5189 |
Secondary
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment
Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\]
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 4659 mg•h/dL | Standard Deviation 2854 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC | 2712 mg•h/dL | Standard Deviation 5010 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 8786 mg•h/dL | Standard Deviation 4201 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC | 1541 mg•h/dL | Standard Deviation 5815 |
| Placebo | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | -1376 mg•h/dL | Standard Deviation 2205 |
| Placebo | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC | -6128 mg•h/dL | Standard Deviation 4998 |
Secondary
Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function
Area under the plasma concentration time curve (AUC) from time point zero (baseline) to the last quantifiable time-point before the analyte first returns to baseline \[AUC0 - last\]
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 4513 mg•h/dL | Standard Deviation 2701 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC | -2130 mg•h/dL | Standard Deviation 4691 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 8609 mg•h/dL | Standard Deviation 4500 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC | 3609 mg•h/dL | Standard Deviation 10232 |
| Placebo | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 1632 mg•h/dL | Standard Deviation 3235 |
| Placebo | Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC | -542 mg•h/dL | Standard Deviation 4480 |
Secondary
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants
AUC from baseline to time point t (AUC0-t)
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | apoA-I (0-24h) | 496 mg•h/dL | Standard Deviation 212 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | apoA-I (0-48h) | 731 mg•h/dL | Standard Deviation 447 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | apoA-I (0-72h) | 880 mg•h/dL | Standard Deviation 726 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | apoA-I (0-96h) | 1006 mg•h/dL | Standard Deviation 1104 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | apoA-I (0-168h) | 1009 mg•h/dL | Standard Deviation 1761 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | PC (0-24h) | 508 mg•h/dL | Standard Deviation 349 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | PC (0-48h) | 466 mg•h/dL | Standard Deviation 744 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | PC (0-72h) | 418 mg•h/dL | Standard Deviation 1251 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | PC (0-96h) | 389 mg•h/dL | Standard Deviation 1841 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | PC (0-168h) | -405 mg•h/dL | Standard Deviation 3636 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | PC (0-96h) | 1712 mg•h/dL | Standard Deviation 1694 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | apoA-I (0-24h) | 1929 mg•h/dL | Standard Deviation 557 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | PC (0-24h) | 1545 mg•h/dL | Standard Deviation 552 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | apoA-I (0-168h) | 4734 mg•h/dL | Standard Deviation 2382 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | apoA-I (0-48h) | 2903 mg•h/dL | Standard Deviation 944 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | PC (0-168h) | 1273 mg•h/dL | Standard Deviation 2764 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | PC (0-72h) | 1713 mg•h/dL | Standard Deviation 1209 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | apoA-I (0-72h) | 3516 mg•h/dL | Standard Deviation 1248 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | PC (0-48h) | 1627 mg•h/dL | Standard Deviation 872 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | apoA-I (0-96h) | 3943 mg•h/dL | Standard Deviation 1581 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | PC (0-72h) | -549 mg•h/dL | Standard Deviation 886 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | apoA-I (0-96h) | -541 mg•h/dL | Standard Deviation 940 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | apoA-I (0-168h) | -452 mg•h/dL | Standard Deviation 1498 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | PC (0-24h) | -92 mg•h/dL | Standard Deviation 229 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | PC (0-96h) | -780 mg•h/dL | Standard Deviation 1346 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | PC (0-48h) | -315 mg•h/dL | Standard Deviation 522 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | apoA-I (0-24h) | -168 mg•h/dL | Standard Deviation 158 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | PC (0-168h) | -1494 mg•h/dL | Standard Deviation 2501 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | apoA-I (0-48h) | -331 mg•h/dL | Standard Deviation 375 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants | apoA-I (0-72h) | -439 mg•h/dL | Standard Deviation 632 |
Secondary
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment
AUC from baseline to time point t (AUC0-t)
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC (0-96h) | 1227 mg•h/dL | Standard Deviation 2058 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC (0-24h) | 678 mg•h/dL | Standard Deviation 386 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I (0-24h) | 589 mg•h/dL | Standard Deviation 263 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC (0-72h) | 956 mg•h/dL | Standard Deviation 1393 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC (0-48h) | 845 mg•h/dL | Standard Deviation 797 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I (0-96h) | 1376 mg•h/dL | Standard Deviation 1468 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I (0-72h) | 1179 mg•h/dL | Standard Deviation 946 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC (0-168h) | 1018 mg•h/dL | Standard Deviation 4052 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I (0-168h) | 1196 mg•h/dL | Standard Deviation 2155 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I (0-48h) | 949 mg•h/dL | Standard Deviation 560 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC (0-48h) | 1968 mg•h/dL | Standard Deviation 623 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I (0-72h) | 3998 mg•h/dL | Standard Deviation 1152 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I (0-96h) | 4517 mg•h/dL | Standard Deviation 1465 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I (0-168h) | 5624 mg•h/dL | Standard Deviation 2293 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC (0-24h) | 1777 mg•h/dL | Standard Deviation 353 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I (0-48h) | 3308 mg•h/dL | Standard Deviation 847 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC (0-72h) | 2093 mg•h/dL | Standard Deviation 950 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC (0-96h) | 2194 mg•h/dL | Standard Deviation 1351 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC (0-168h) | 2004 mg•h/dL | Standard Deviation 3214 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I (0-24h) | 2219 mg•h/dL | Standard Deviation 515 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I (0-168h) | -865 mg•h/dL | Standard Deviation 1824 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I (0-48h) | -370 mg•h/dL | Standard Deviation 514 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC (0-96h) | -1329 mg•h/dL | Standard Deviation 1769 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I (0-96h) | -576 mg•h/dL | Standard Deviation 1188 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I (0-24h) | -218 mg•h/dL | Standard Deviation 238 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC (0-168h) | 2203 mg•h/dL | Standard Deviation 3197 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC (0-48h) | -523 mg•h/dL | Standard Deviation 705 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC (0-24h) | -212 mg•h/dL | Standard Deviation 348 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I (0-72h) | -451 mg•h/dL | Standard Deviation 834 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC (0-72h) | -871 mg•h/dL | Standard Deviation 1196 |
Secondary
Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function
AUC from baseline to time point t (AUC0-t)
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I (0-24h) | 418 mg•h/dL | Standard Deviation 117 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I (0-48h) | 547 mg•h/dL | Standard Deviation 204 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I (0-72h) | 628 mg•h/dL | Standard Deviation 337 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I (0-96h) | 692 mg•h/dL | Standard Deviation 554 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I (0-168h) | 821 mg•h/dL | Standard Deviation 1387 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC (0-24h) | 364 mg•h/dL | Standard Deviation 245 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC (0-48h) | 145 mg•h/dL | Standard Deviation 536 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC (0-72h) | -38 mg•h/dL | Standard Deviation 946 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC (0-96h) | -256 mg•h/dL | Standard Deviation 1415 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC (0-168h) | -1511 mg•h/dL | Standard Deviation 3053 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC (0-96h) | 1218 mg•h/dL | Standard Deviation 2005 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I (0-24h) | 1653 mg•h/dL | Standard Deviation 496 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC (0-24h) | 1347 mg•h/dL | Standard Deviation 661 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I (0-168h) | 3780 mg•h/dL | Standard Deviation 2353 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I (0-48h) | 2521 mg•h/dL | Standard Deviation 955 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC (0-168h) | 437 mg•h/dL | Standard Deviation 2061 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC (0-72h) | 1325 mg•h/dL | Standard Deviation 1421 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I (0-72h) | 3064 mg•h/dL | Standard Deviation 1280 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC (0-48h) | 1294 mg•h/dL | Standard Deviation 1025 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I (0-96h) | 3342 mg•h/dL | Standard Deviation 1642 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC (0-72h) | -426 mg•h/dL | Standard Deviation 759 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I (0-96h) | -528 mg•h/dL | Standard Deviation 883 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I (0-168h) | -275 mg•h/dL | Standard Deviation 1461 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC (0-24h) | -46 mg•h/dL | Standard Deviation 160 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC (0-96h) | -569 mg•h/dL | Standard Deviation 1162 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC (0-48h) | -235 mg•h/dL | Standard Deviation 441 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I (0-24h) | -149 mg•h/dL | Standard Deviation 123 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC (0-168h) | -1089 mg•h/dL | Standard Deviation 2188 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I (0-48h) | -316 mg•h/dL | Standard Deviation 332 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I (0-72h) | -435 mg•h/dL | Standard Deviation 579 |
Secondary
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants
AUC from baseline to time point t (AUC0-t)
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | PC (0-48h) | 472 mg•h/dL | Standard Deviation 1293 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | PC (0-72h) | 509 mg•h/dL | Standard Deviation 1989 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | apoA-I (0-72h) | 2195 mg•h/dL | Standard Deviation 1177 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | PC (0-96h) | 518 mg•h/dL | Standard Deviation 2679 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | PC (0-168h) | -625 mg•h/dL | Standard Deviation 4963 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | apoA-I (0-24h) | 881 mg•h/dL | Standard Deviation 422 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | apoA-I (0-96h) | 2741 mg•h/dL | Standard Deviation 1526 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | apoA-I (0-48h) | 1593 mg•h/dL | Standard Deviation 798 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | apoA-I (0-168h) | 3997 mg•h/dL | Standard Deviation 2655 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | PC (0-24h) | 462 mg•h/dL | Standard Deviation 681 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | PC (0-48h) | 1765 mg•h/dL | Standard Deviation 1948 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | apoA-I (0-96h) | 6000 mg•h/dL | Standard Deviation 2292 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | PC (0-72h) | 1899 mg•h/dL | Standard Deviation 2823 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | PC (0-24h) | 1564 mg•h/dL | Standard Deviation 1051 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | apoA-I (0-24h) | 2392 mg•h/dL | Standard Deviation 655 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | PC (0-96h) | 1951 mg•h/dL | Standard Deviation 3681 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | apoA-I (0-72h) | 5050 mg•h/dL | Standard Deviation 1794 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | apoA-I (0-168h) | 8865 mg•h/dL | Standard Deviation 3200 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | PC (0-168h) | 2655 mg•h/dL | Standard Deviation 6024 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | apoA-I (0-48h) | 3913 mg•h/dL | Standard Deviation 1235 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | PC (0-168h) | -442 mg•h/dL | Standard Deviation 6319 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | apoA-I (0-24h) | -57 mg•h/dL | Standard Deviation 377 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | apoA-I (0-48h) | -55 mg•h/dL | Standard Deviation 759 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | apoA-I (0-72h) | -6 mg•h/dL | Standard Deviation 1160 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | apoA-I (0-96h) | 90 mg•h/dL | Standard Deviation 1590 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | apoA-I (0-168h) | 1635 mg•h/dL | Standard Deviation 3540 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | PC (0-24h) | -488 mg•h/dL | Standard Deviation 772 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | PC (0-72h) | -1173 mg•h/dL | Standard Deviation 2168 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | PC (0-96h) | -1417 mg•h/dL | Standard Deviation 2894 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants | PC (0-48h) | -902 mg•h/dL | Standard Deviation 1433 |
Secondary
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment
AUC from baseline to time point t (AUC0-t)
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I (0-24h) | 823 mg•h/dL | Standard Deviation 466 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I (0-48h) | 1503 mg•h/dL | Standard Deviation 881 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I (0-72h) | 2128 mg•h/dL | Standard Deviation 1304 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I (0-96h) | 2707 mg•h/dL | Standard Deviation 1669 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I (0-168h) | 4229 mg•h/dL | Standard Deviation 2754 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC (0-24h) | 789 mg•h/dL | Standard Deviation 760 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC (0-48h) | 1110 mg•h/dL | Standard Deviation 1402 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC (0-72h) | 1487 mg•h/dL | Standard Deviation 2090 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC (0-96h) | 1826 mg•h/dL | Standard Deviation 2706 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC (0-168h) | 2603 mg•h/dL | Standard Deviation 4295 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC (0-96h) | 1751 mg•h/dL | Standard Deviation 2867 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I (0-24h) | 2469 mg•h/dL | Standard Deviation 573 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC (0-24h) | 1518 mg•h/dL | Standard Deviation 799 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I (0-168h) | 8840 mg•h/dL | Standard Deviation 3678 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I (0-48h) | 4049 mg•h/dL | Standard Deviation 1221 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC (0-168h) | 1316 mg•h/dL | Standard Deviation 4998 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC (0-72h) | 1726 mg•h/dL | Standard Deviation 2176 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I (0-72h) | 5226 mg•h/dL | Standard Deviation 1910 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC (0-48h) | 1650 mg•h/dL | Standard Deviation 1474 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I (0-96h) | 6212 mg•h/dL | Standard Deviation 2503 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC (0-72h) | -2536 mg•h/dL | Standard Deviation 1731 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I (0-96h) | -796 mg•h/dL | Standard Deviation 1045 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I (0-168h) | -4322 mg•h/dL | Standard Deviation 0 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC (0-24h) | -950 mg•h/dL | Standard Deviation 405 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC (0-96h) | -3297 mg•h/dL | Standard Deviation 2471 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC (0-48h) | -1810 mg•h/dL | Standard Deviation 1001 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I (0-24h) | -243 mg•h/dL | Standard Deviation 170 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC (0-168h) | -12308 mg•h/dL | Standard Deviation 0 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I (0-48h) | -440 mg•h/dL | Standard Deviation 436 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I (0-72h) | -617 mg•h/dL | Standard Deviation 741 |
Secondary
Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function
AUC from baseline to time point t (AUC0-t)
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I (0-24h) | 929 mg•h/dL | Standard Deviation 396 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I (0-48h) | 1668 mg•h/dL | Standard Deviation 753 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I (0-72h) | 2252 mg•h/dL | Standard Deviation 1116 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I (0-96h) | 2769 mg•h/dL | Standard Deviation 1473 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I (0-168h) | 3811 mg•h/dL | Standard Deviation 2706 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC (0-24h) | 189 mg•h/dL | Standard Deviation 483 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC (0-48h) | -59 mg•h/dL | Standard Deviation 952 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC (0-72h) | -306 mg•h/dL | Standard Deviation 1544 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC (0-96h) | -573 mg•h/dL | Standard Deviation 2204 |
| CSL112 (2 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC (0-168h) | -3853 mg•h/dL | Standard Deviation 3242 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC (0-96h) | 2078 mg•h/dL | Standard Deviation 4905 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I (0-24h) | 2098 mg•h/dL | Standard Deviation 463 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC (0-24h) | 1524 mg•h/dL | Standard Deviation 1388 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I (0-168h) | 8342 mg•h/dL | Standard Deviation 2549 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I (0-48h) | 3459 mg•h/dL | Standard Deviation 1001 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC (0-168h) | 4584 mg•h/dL | Standard Deviation 7822 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC (0-72h) | 2000 mg•h/dL | Standard Deviation 3773 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I (0-72h) | 4497 mg•h/dL | Standard Deviation 1478 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC (0-48h) | 1796 mg•h/dL | Standard Deviation 2613 |
| CSL112 (6 g) | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I (0-96h) | 5360 mg•h/dL | Standard Deviation 1909 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC (0-72h) | -605 mg•h/dL | Standard Deviation 2133 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I (0-96h) | 459 mg•h/dL | Standard Deviation 1666 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I (0-168h) | 2486 mg•h/dL | Standard Deviation 2804 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC (0-24h) | -295 mg•h/dL | Standard Deviation 819 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC (0-96h) | -633 mg•h/dL | Standard Deviation 2772 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC (0-48h) | -523 mg•h/dL | Standard Deviation 1446 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I (0-24h) | 20 mg•h/dL | Standard Deviation 417 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC (0-168h) | 1253 mg•h/dL | Standard Deviation 4446 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I (0-48h) | 105 mg•h/dL | Standard Deviation 820 |
| Placebo | Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I (0-72h) | 249 mg•h/dL | Standard Deviation 1232 |
Secondary
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for All Participants
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for All Participants | apoA-I | 0.29 L/h | Standard Deviation 0.27 |
| CSL112 (2 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for All Participants | PC | 0.32 L/h | Standard Deviation 0.26 |
| CSL112 (6 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for All Participants | apoA-I | 0.15 L/h | Standard Deviation 0.13 |
| CSL112 (6 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for All Participants | PC | 0.61 L/h | Standard Deviation 0.26 |
Secondary
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I | 0.27 L/h | Standard Deviation 0.35 |
| CSL112 (2 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC | 0.26 L/h | Standard Deviation 0.23 |
| CSL112 (6 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I | 0.09 L/h | Standard Deviation 0.05 |
| CSL112 (6 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC | 0.54 L/h | Standard Deviation 0.13 |
Secondary
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Normal Renal Function
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I | 0.33 L/h | Standard Deviation 0.01 |
| CSL112 (2 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC | 0.41 L/h | Standard Deviation 0.38 |
| CSL112 (6 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I | 0.19 L/h | Standard Deviation 0.17 |
| CSL112 (6 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC | 0.68 L/h | Standard Deviation 0.35 |
Secondary
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for All Participants
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 0.09 L/h | Standard Deviation 0.1 |
| CSL112 (2 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for All Participants | PC | 0.11 L/h | Standard Deviation 0.09 |
| CSL112 (6 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 0.07 L/h | Standard Deviation 0.02 |
| CSL112 (6 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for All Participants | PC | 0.57 L/h | Standard Deviation 1.12 |
Secondary
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 0.05 L/h | Standard Deviation 0.02 |
| CSL112 (2 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC | 0.08 L/h | Standard Deviation 0.07 |
| CSL112 (6 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 0.08 L/h | Standard Deviation 0.03 |
| CSL112 (6 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC | 1.01 L/h | Standard Deviation 1.63 |
Secondary
Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 0.11 L/h | Standard Deviation 0.12 |
| CSL112 (2 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC | 0.24 L/h | Standard Deviation 0 |
| CSL112 (6 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 0.08 L/h | Standard Deviation 0.02 |
| CSL112 (6 g) | Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC | 0.19 L/h | Standard Deviation 0.12 |
Secondary
Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for All Participants
Cmax is the maximal plasma concentration.
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: The Pharmacokinetic/Pharmacodynamic (PK/PD) population was a subset of subjects from the main study who consented to participate in the PK/PD substudy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for All Participants | apoA-I | 42.6 mg/dL | Standard Deviation 11.2 |
| CSL112 (2 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for All Participants | PC | 67.7 mg/dL | Standard Deviation 19.2 |
| CSL112 (6 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for All Participants | apoA-I | 147.4 mg/dL | Standard Deviation 31.9 |
| CSL112 (6 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for All Participants | PC | 196.4 mg/dL | Standard Deviation 36.2 |
| Placebo | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for All Participants | apoA-I | 7.1 mg/dL | Standard Deviation 7.9 |
| Placebo | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for All Participants | PC | 11.1 mg/dL | Standard Deviation 15.2 |
Secondary
Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment
Cmax is the maximal plasma concentration.
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I | 44.6 mg/dL | Standard Deviation 10.2 |
| CSL112 (2 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC | 74.6 mg/dL | Standard Deviation 14.7 |
| CSL112 (6 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I | 160.7 mg/dL | Standard Deviation 37 |
| CSL112 (6 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC | 211.3 mg/dL | Standard Deviation 37.5 |
| Placebo | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I | 5.2 mg/dL | Standard Deviation 7.3 |
| Placebo | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC | 6.0 mg/dL | Standard Deviation 10.8 |
Secondary
Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function
Cmax is the maximal plasma concentration.
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I | 40.9 mg/dL | Standard Deviation 12 |
| CSL112 (2 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC | 61.9 mg/dL | Standard Deviation 21 |
| CSL112 (6 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I | 135.1 mg/dL | Standard Deviation 22.8 |
| CSL112 (6 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC | 184.9 mg/dL | Standard Deviation 31.5 |
| Placebo | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I | 7.8 mg/dL | Standard Deviation 8.3 |
| Placebo | Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC | 13.0 mg/dL | Standard Deviation 16.5 |
Secondary
Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for All Participants
Cmax is the maximal plasma concentration.
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 57.6 mg/dL | Standard Deviation 19.5 |
| CSL112 (2 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for All Participants | PC | 59.0 mg/dL | Standard Deviation 34.2 |
| CSL112 (6 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 164.3 mg/dL | Standard Deviation 33.4 |
| CSL112 (6 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for All Participants | PC | 187.4 mg/dL | Standard Deviation 49.9 |
| Placebo | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 12.7 mg/dL | Standard Deviation 19.5 |
| Placebo | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for All Participants | PC | 9.1 mg/dL | Standard Deviation 43.1 |
Secondary
Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment
Cmax is the maximal plasma concentration.
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 53.7 mg/dL | Standard Deviation 20.1 |
| CSL112 (2 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC | 74.8 mg/dL | Standard Deviation 37 |
| CSL112 (6 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 169.7 mg/dL | Standard Deviation 29.3 |
| CSL112 (6 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC | 190.4 mg/dL | Standard Deviation 46.7 |
| Placebo | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 1.0 mg/dL | Standard Deviation 12.1 |
| Placebo | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC | -17.4 mg/dL | Standard Deviation 28.9 |
Secondary
Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function
Cmax is the maximal plasma concentration.
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 60.8 mg/dL | Standard Deviation 19.2 |
| CSL112 (2 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC | 45.8 mg/dL | Standard Deviation 26.4 |
| CSL112 (6 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 149.0 mg/dL | Standard Deviation 26.9 |
| CSL112 (6 g) | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC | 176.1 mg/dL | Standard Deviation 54 |
| Placebo | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 17.5 mg/dL | Standard Deviation 20.3 |
| Placebo | Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC | 20.1 mg/dL | Standard Deviation 44.2 |
Secondary
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Mild Renal Impairment
apoA-I and PC are analytes of CSL112
Time frame: Before first infusion and end of first infusion
Population: PK
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Mild Renal Impairment | apoA-I | 35.9 mg/dL | Standard Deviation 19.05 |
| CSL112 (2 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Mild Renal Impairment | PC | 57.8 mg/dL | Standard Deviation 24.71 |
| CSL112 (6 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Mild Renal Impairment | apoA-I | 135.5 mg/dL | Standard Deviation 59.05 |
| CSL112 (6 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Mild Renal Impairment | PC | 180.6 mg/dL | Standard Deviation 79.5 |
| Placebo | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Mild Renal Impairment | apoA-I | -5.3 mg/dL | Standard Deviation 9.7 |
| Placebo | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Mild Renal Impairment | PC | -0.8 mg/dL | Standard Deviation 14.95 |
Secondary
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Normal Renal Function
apoA-I and PC are analytes of CSL112
Time frame: Before first infusion and end of first infusion
Population: PK
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Normal Renal Function | apoA-I | 36.0 mg/dL | Standard Deviation 25.35 |
| CSL112 (2 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Normal Renal Function | PC | 58.0 mg/dL | Standard Deviation 37.06 |
| CSL112 (6 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Normal Renal Function | apoA-I | 134.5 mg/dL | Standard Deviation 48.25 |
| CSL112 (6 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Normal Renal Function | PC | 177.4 mg/dL | Standard Deviation 67.93 |
| Placebo | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Normal Renal Function | apoA-I | -4.0 mg/dL | Standard Deviation 16.95 |
| Placebo | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Normal Renal Function | PC | -1.3 mg/dL | Standard Deviation 25.74 |
Secondary
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for All Participants
Time frame: Before first infusion and end of fourth infusion
Population: PK
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for All Participants | apoA-I | 52.1 mg/dL | Standard Deviation 55.03 |
| CSL112 (2 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for All Participants | PC | 48.7 mg/dL | Standard Deviation 55.75 |
| CSL112 (6 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for All Participants | apoA-I | 158.0 mg/dL | Standard Deviation 55.07 |
| CSL112 (6 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for All Participants | PC | 186.8 mg/dL | Standard Deviation 79.39 |
| Placebo | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for All Participants | apoA-I | 5.4 mg/dL | Standard Deviation 26.47 |
| Placebo | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for All Participants | PC | -12.9 mg/dL | Standard Deviation 42.05 |
Secondary
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Mild Renal Impairment
apoA-I and PC are analytes of CSL112
Time frame: Before first infusion and end of fourth infusion
Population: PK
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 49.3 mg/dL | Standard Deviation 27.63 |
| CSL112 (2 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Mild Renal Impairment | PC | 50.6 mg/dL | Standard Deviation 47.17 |
| CSL112 (6 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 158.4 mg/dL | Standard Deviation 56.19 |
| CSL112 (6 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Mild Renal Impairment | PC | 188.3 mg/dL | Standard Deviation 79.39 |
| Placebo | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 6.0 mg/dL | Standard Deviation 25.68 |
| Placebo | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Mild Renal Impairment | PC | -13.2 mg/dL | Standard Deviation 40.08 |
Secondary
Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Normal Renal Function
apoA-I and PC are analytes of CSL112
Time frame: Before first infusion and end of fourth infusion
Population: PK
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Normal Renal Function | apoA-I | 54.7 mg/dL | Standard Deviation 74.94 |
| CSL112 (2 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Normal Renal Function | PC | 47.6 mg/dL | Standard Deviation 64.67 |
| CSL112 (6 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Normal Renal Function | apoA-I | 154.3 mg/dL | Standard Deviation 53.64 |
| CSL112 (6 g) | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Normal Renal Function | PC | 182.0 mg/dL | Standard Deviation 80.74 |
| Placebo | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Normal Renal Function | apoA-I | 4.8 mg/dL | Standard Deviation 28.19 |
| Placebo | Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Normal Renal Function | PC | -12.3 mg/dL | Standard Deviation 44.89 |
Secondary
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for All Participants
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for All Participants | apoA-I | 46.4 hours | Standard Deviation 33.1 |
| CSL112 (2 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for All Participants | PC | 32.9 hours | Standard Deviation 29.6 |
| CSL112 (6 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for All Participants | apoA-I | 53.9 hours | Standard Deviation 38.7 |
| CSL112 (6 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for All Participants | PC | 9.7 hours | Standard Deviation 7.2 |
| Placebo | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for All Participants | PC | 241.2 hours | Standard Deviation 0 |
Secondary
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I | 65.9 hours | Standard Deviation 17.5 |
| CSL112 (2 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC | 31.8 hours | Standard Deviation 37.7 |
| CSL112 (6 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I | 66.4 hours | Standard Deviation 51.4 |
| CSL112 (6 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC | 7.1 hours | Standard Deviation 4.4 |
| Placebo | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC | 241.2 hours | Standard Deviation 0 |
Secondary
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Normal Renal Function
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I | 7.5 hours | Standard Deviation 1.7 |
| CSL112 (2 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC | 34 hours | Standard Deviation 27.7 |
| CSL112 (6 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I | 41.4 hours | Standard Deviation 24.1 |
| CSL112 (6 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC | 12.3 hours | Standard Deviation 8.9 |
Secondary
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for All Participants
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 269.1 hours | Standard Deviation 292 |
| CSL112 (2 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for All Participants | PC | 21.5 hours | Standard Deviation 20.6 |
| CSL112 (6 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 103.6 hours | Standard Deviation 61.1 |
| CSL112 (6 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for All Participants | PC | 156.3 hours | Standard Deviation 245.8 |
| Placebo | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 145 hours | Standard Deviation 0 |
Secondary
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC | 46.3 hours | Standard Deviation 2.2 |
| CSL112 (2 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 263.1 hours | Standard Deviation 285.4 |
| CSL112 (6 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 99.2 hours | Standard Deviation 68.2 |
| CSL112 (6 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC | 185.6 hours | Standard Deviation 306.5 |
Secondary
Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 271.6 hours | Standard Deviation 317.4 |
| CSL112 (2 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC | 9.1 hours | Standard Deviation 9.3 |
| CSL112 (6 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 96.5 hours | Standard Deviation 47.3 |
| CSL112 (6 g) | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC | 121.1 hours | Standard Deviation 102.7 |
| Placebo | Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 145 hours | Standard Deviation 0 |
Secondary
Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for All Participants
Tmax is time to maximal plasma concentration
Time frame: Before and for 7 days after the first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for All Participants | apoA-I | 2.23 hours |
| CSL112 (2 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for All Participants | PC | 2.23 hours |
| CSL112 (6 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for All Participants | apoA-I | 2.17 hours |
| CSL112 (6 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for All Participants | PC | 2.17 hours |
| Placebo | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for All Participants | apoA-I | 46.8 hours |
| Placebo | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for All Participants | PC | 5.29 hours |
Secondary
Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment
Tmax is time to maximal plasma concentration
Time frame: Before and for 7 days after the first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I | 2.18 hours |
| CSL112 (2 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC | 2.28 hours |
| CSL112 (6 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I | 2.22 hours |
| CSL112 (6 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC | 2.22 hours |
| Placebo | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I | 0 hours |
| Placebo | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC | 0 hours |
Secondary
Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function
Tmax is time to maximal plasma concentration
Time frame: Before and for 7 days after the first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I | 2.25 hours |
| CSL112 (2 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC | 2.22 hours |
| CSL112 (6 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I | 2.17 hours |
| CSL112 (6 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC | 2.17 hours |
| Placebo | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I | 96.1 hours |
| Placebo | Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC | 8.1 hours |
Secondary
Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for All Participants
Tmax is time to maximal plasma concentration
Time frame: Before and for 7 days after the fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 2.13 hours |
| CSL112 (2 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for All Participants | PC | 2.17 hours |
| CSL112 (6 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 2.25 hours |
| CSL112 (6 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for All Participants | PC | 2.25 hours |
| Placebo | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 119 hours |
| Placebo | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for All Participants | PC | 46.93 hours |
Secondary
Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment
Tmax is time to maximal plasma concentration
Time frame: Before and for 7 days after the fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 2.17 hours |
| CSL112 (2 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC | 2.17 hours |
| CSL112 (6 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 2.25 hours |
| CSL112 (6 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC | 2.25 hours |
| Placebo | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 72.5 hours |
| Placebo | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC | 48.3 hours |
Secondary
Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function
Tmax is time to maximal plasma concentration
Time frame: Before and for 7 days after the fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 2.13 hours |
| CSL112 (2 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC | 2.17 hours |
| CSL112 (6 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 2.17 hours |
| CSL112 (6 g) | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC | 2.17 hours |
| Placebo | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 119.3 hours |
| Placebo | Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC | 29 hours |
Secondary
Change From Baseline in Plasma Volume of Distribution at Steady State (Vss) for apoA-I and PC After First Infusion for All Participants
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Volume of Distribution at Steady State (Vss) for apoA-I and PC After First Infusion for All Participants | apoA-I | 33.4 Liters | Standard Deviation 64.7 |
| CSL112 (2 g) | Change From Baseline in Plasma Volume of Distribution at Steady State (Vss) for apoA-I and PC After First Infusion for All Participants | PC | 6.1 Liters | Standard Deviation 4.4 |
| CSL112 (6 g) | Change From Baseline in Plasma Volume of Distribution at Steady State (Vss) for apoA-I and PC After First Infusion for All Participants | apoA-I | 7.4 Liters | Standard Deviation 3.1 |
| CSL112 (6 g) | Change From Baseline in Plasma Volume of Distribution at Steady State (Vss) for apoA-I and PC After First Infusion for All Participants | PC | 14.4 Liters | Standard Deviation 33.3 |
Secondary
Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I | 48.2 Liters | Standard Deviation 78.1 |
| CSL112 (2 g) | Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC | 4.7 Liters | Standard Deviation 1.3 |
| CSL112 (6 g) | Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | apoA-I | 6.4 Liters | Standard Deviation 2.3 |
| CSL112 (6 g) | Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment | PC | 4 Liters | Standard Deviation 1.5 |
Secondary
Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Normal Renal Function
Time frame: Before first infusion (baseline) and for up to approximately 7 days after first infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I | 3.8 Liters | Standard Deviation 0.9 |
| CSL112 (2 g) | Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC | 8.3 Liters | Standard Deviation 7.7 |
| CSL112 (6 g) | Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Normal Renal Function | apoA-I | 8.1 Liters | Standard Deviation 3.8 |
| CSL112 (6 g) | Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Normal Renal Function | PC | 24.7 Liters | Standard Deviation 47.2 |
Secondary
Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for All Participants
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 18.7 Liters | Standard Deviation 16.6 |
| CSL112 (2 g) | Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for All Participants | PC | 10.7 Liters | Standard Deviation 7.5 |
| CSL112 (6 g) | Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for All Participants | apoA-I | 9.4 Liters | Standard Deviation 4.7 |
| CSL112 (6 g) | Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for All Participants | PC | 58.3 Liters | Standard Deviation 94.9 |
Secondary
Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 18.7 Liters | Standard Deviation 21.3 |
| CSL112 (2 g) | Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC | 9.3 Liters | Standard Deviation 8.2 |
| CSL112 (6 g) | Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | apoA-I | 9.4 Liters | Standard Deviation 5.9 |
| CSL112 (6 g) | Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment | PC | 83.1 Liters | Standard Deviation 114 |
Secondary
Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function
Time frame: Before first infusion (baseline) and for up to approximately 7 days after fourth infusion
Population: PK/PD
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 18.7 Liters | Standard Deviation 16.1 |
| CSL112 (2 g) | Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC | 11.4 Liters | Standard Deviation 8.3 |
| CSL112 (6 g) | Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | apoA-I | 9.4 Liters | Standard Deviation 2.5 |
| CSL112 (6 g) | Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function | PC | 17 Liters | Standard Deviation 10.3 |
Secondary
Change From Baseline in Serum Antibodies to CSL112 and apoA-I
Time frame: Before first infusion, up to approximately Day 112
Population: SP
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL112 (2 g) | Change From Baseline in Serum Antibodies to CSL112 and apoA-I | Anti-CSL112 antibody | 0 Titer | Standard Deviation 0.14 |
| CSL112 (2 g) | Change From Baseline in Serum Antibodies to CSL112 and apoA-I | Anti-apoA-I antibody | 0 Titer | Standard Deviation 0.09 |
| CSL112 (6 g) | Change From Baseline in Serum Antibodies to CSL112 and apoA-I | Anti-CSL112 antibody | 0 Titer | Standard Deviation 0.2 |
| CSL112 (6 g) | Change From Baseline in Serum Antibodies to CSL112 and apoA-I | Anti-apoA-I antibody | 0 Titer | Standard Deviation 0.14 |
| Placebo | Change From Baseline in Serum Antibodies to CSL112 and apoA-I | Anti-CSL112 antibody | 0 Titer | Standard Deviation 0.2 |
| Placebo | Change From Baseline in Serum Antibodies to CSL112 and apoA-I | Anti-apoA-I antibody | 0 Titer | Standard Deviation 0.1 |
Secondary
Number of Participants With Parvovirus B19 DNA in Serum
Time frame: Study Day 112
Population: Serology population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CSL112 (2 g) | Number of Participants With Parvovirus B19 DNA in Serum | Not detected | 57 participants |
| CSL112 (2 g) | Number of Participants With Parvovirus B19 DNA in Serum | Missing | 2 participants |
| CSL112 (2 g) | Number of Participants With Parvovirus B19 DNA in Serum | < 101 IU/mL | 1 participants |
| CSL112 (6 g) | Number of Participants With Parvovirus B19 DNA in Serum | < 101 IU/mL | 0 participants |
| CSL112 (6 g) | Number of Participants With Parvovirus B19 DNA in Serum | Missing | 0 participants |
| CSL112 (6 g) | Number of Participants With Parvovirus B19 DNA in Serum | Not detected | 60 participants |
| Placebo | Number of Participants With Parvovirus B19 DNA in Serum | Missing | 0 participants |
| Placebo | Number of Participants With Parvovirus B19 DNA in Serum | Not detected | 59 participants |
| Placebo | Number of Participants With Parvovirus B19 DNA in Serum | < 101 IU/mL | 1 participants |
Secondary
Number of Participants With Positive Serology Results for IgG and IgM Antibodies to Parvovirus B19
Time frame: Study Day 112
Population: Serology population are a random subset of participants that was selected and had their samples tested for the presence of parvovirus B19.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CSL112 (2 g) | Number of Participants With Positive Serology Results for IgG and IgM Antibodies to Parvovirus B19 | IgG | 40 participants |
| CSL112 (2 g) | Number of Participants With Positive Serology Results for IgG and IgM Antibodies to Parvovirus B19 | IgM | 0 participants |
| CSL112 (6 g) | Number of Participants With Positive Serology Results for IgG and IgM Antibodies to Parvovirus B19 | IgG | 48 participants |
| CSL112 (6 g) | Number of Participants With Positive Serology Results for IgG and IgM Antibodies to Parvovirus B19 | IgM | 0 participants |
| Placebo | Number of Participants With Positive Serology Results for IgG and IgM Antibodies to Parvovirus B19 | IgG | 44 participants |
| Placebo | Number of Participants With Positive Serology Results for IgG and IgM Antibodies to Parvovirus B19 | IgM | 0 participants |
Secondary
Percent of Participants Who Experience Bleeding Events
The number of subjects who experience bleeding events as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al, 2011)
Time frame: From the start of first infusion, up to approximately Day 112
Population: SP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL112 (2 g) | Percent of Participants Who Experience Bleeding Events | 9.2 percentage of participants |
| CSL112 (6 g) | Percent of Participants Who Experience Bleeding Events | 9.1 percentage of participants |
| Placebo | Percent of Participants Who Experience Bleeding Events | 12.3 percentage of participants |
Secondary
Percent of Participants With Any Adverse Event (AE)
Time frame: From the start of first infusion, up to approximately Day 382
Population: SP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL112 (2 g) | Percent of Participants With Any Adverse Event (AE) | 50.6 percentage of participants |
| CSL112 (6 g) | Percent of Participants With Any Adverse Event (AE) | 51.4 percentage of participants |
| Placebo | Percent of Participants With Any Adverse Event (AE) | 49.6 percentage of participants |
Secondary
Percent of Participants With the Occurrence of Suspected Adverse Drug Reactions
The overall percentage of subjects: * with adverse events (AEs), including local tolerability events, that begin during or within 1 hour of an infusion; or * with AEs considered to be causally related to the test product; or * who experience an AE for which the incidence rate in an active treatment arm exceeds the exposure-adjusted incidence rate in the placebo arm by 30% or more, provided the difference in incidence rates is 1% or more.
Time frame: From the start of first infusion, up to approximately Day 382
Population: SP
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL112 (2 g) | Percent of Participants With the Occurrence of Suspected Adverse Drug Reactions | 31.8 percentage of participants |
| CSL112 (6 g) | Percent of Participants With the Occurrence of Suspected Adverse Drug Reactions | 28.4 percentage of participants |
| Placebo | Percent of Participants With the Occurrence of Suspected Adverse Drug Reactions | 23.5 percentage of participants |
Secondary
The Percentage of Participants With a Time-to-first Major Adverse Cardiovascular Event (MACE)
The MACE is a 4-component composite comprised of the time to the first of the following events: CV death, nonfatal myocardial infarction, ischemic stroke (non-hemorrhagic), and hospitalization for unstable angina.
Time frame: From the start of the first infusion up to approximately 382 days
Population: The Intent-to-Treat (ITT) population comprised all subjects who were randomized to one of the three treatment groups for the Main Study or PK/PD substudy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL112 (2 g) | The Percentage of Participants With a Time-to-first Major Adverse Cardiovascular Event (MACE) | 6.4 percentage of participants |
| CSL112 (6 g) | The Percentage of Participants With a Time-to-first Major Adverse Cardiovascular Event (MACE) | 5.7 percentage of participants |
| Placebo | The Percentage of Participants With a Time-to-first Major Adverse Cardiovascular Event (MACE) | 5.5 percentage of participants |
p-value: =0.573395% CI: [0.67, 2.05]Log Rank
p-value: =0.971795% CI: [0.57, 1.8]Log Rank