A Phase 2b Study of CSL112 in Subjects With Acute Myocardial Infarction.

CSL Behring1,267 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

1,267

Conditions

Acute Myocardial Infarction

Interventions

CSL112BIOLOGICAL

CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.

PlaceboBIOLOGICAL

0.9% weight/volume sodium chloride solution (ie, normal saline)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (189)

Outcomes

Primary Outcomes

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.

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.

Secondary Outcomes

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

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

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

Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Normal Renal Function

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Study Site 16101

Birmingham, Alabama, United States

Study Site 16078

Huntsville, Alabama, United States

Study Site - 16168

Concord, California, United States

Study Site 16168

Concord, California, United States

Study Site 16147

Sacramento, California, United States

Study Site 16022

Torrance, California, United States

Study Site 16130

Littleton, Colorado, United States

Study Site 16170

Bridgeport, Connecticut, United States

Study Site 16135

Danbury, Connecticut, United States

Study Site 16148

Clearwater, Florida, United States

...and 179 more locations

apoA-I and PC are analytes of CSL112

Time frame: Before first infusion and end of first infusion

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Percent of Participants With Any Adverse Event (AE)

Time frame: From the start of first infusion, up to approximately Day 382

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

Change From Baseline in Serum Antibodies to CSL112 and apoA-I

Time frame: Before first infusion, up to approximately Day 112

Number of Participants With Positive Serology Results for IgG and IgM Antibodies to Parvovirus B19

Time frame: Study Day 112

Number of Participants With Parvovirus B19 DNA in Serum

Time frame: Study Day 112