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

Phase 2

Completed

Conditions: Acute Myocardial Infarction

Registration Number: NCT02108262

Lead Sponsor: CSL Behring

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1267

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
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.
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.

Secondary Outcome Measures

Name	Time	Method
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.
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 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 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 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 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 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 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 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 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 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 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 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 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 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 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-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 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-∞ 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 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 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.
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 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 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 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 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 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-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 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 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 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 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 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-∞ 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 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 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 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
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)
Number of Participants With Parvovirus B19 DNA in Serum	Study Day 112
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 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 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 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
Percent of Participants With Any Adverse Event (AE)	From the start of first infusion, up to approximately Day 382
Number of Participants With Positive Serology Results for IgG and IgM Antibodies to Parvovirus B19	Study Day 112
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
Change From Baseline in Serum Antibodies to CSL112 and apoA-I	Before first infusion, up to approximately 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.

Trial Locations

Locations (189): Study Site 16101
🇺🇸
Birmingham, Alabama, United States
Study Site 16078
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Huntsville, Alabama, United States
Study Site - 16168
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Concord, California, United States
Study Site 16168
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Concord, California, United States
Study Site 16147
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Sacramento, California, United States
Study Site 16022
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Torrance, California, United States
Study Site 16130
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Littleton, Colorado, United States
Study Site 16170
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Bridgeport, Connecticut, United States
Study Site 16135
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Danbury, Connecticut, United States
Study Site 16148
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Clearwater, Florida, United States
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Study Site 16101
🇺🇸Birmingham, Alabama, United States