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

A Phase 2b, Multi-center, Randomized, Placebo-controlled, Dose-ranging Study to Investigate the Safety and Tolerability of Multiple Dose Administration of CSL112 in Subjects With Acute Myocardial Infarction.

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 Overview

• Status: Completed
• Conditions: Acute Myocardial Infarction
• Intervention / Treatment: Biological: CSL112; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1267
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Study Site 10002
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Study Site 10005
    • Woodville South, South Australia, Australia, 5011
      • Study Site 10012
  • Victoria
    • Epping, Victoria, Australia, 3076
      • Study Site 10006
    • Geelong, Victoria, Australia, 3220
      • Study Site 10007
• Austria
  • Innsbruck, Austria, 6020
    • Study Site 11004
  • Vienna, Austria, 1090
    • Study Site 11002
  • Wien, Austria, 1160
    • Study Site 11001
• Bulgaria
  • Blagoevgrad, Bulgaria, 2700
    • Study Site 12005
  • Burgas, Bulgaria, 8000
    • Study Site 12008
  • Dobrich, Bulgaria, 9300
    • Study Site 12006
  • Haskovo, Bulgaria, 6300
    • Study Site 12021
  • Pazardzhik, Bulgaria, 4400
    • Study Site 12009
  • Pazardzhik, Bulgaria, 4400
    • Study Site 12019
  • Pleven, Bulgaria, 5800
    • Study Site 12016
  • Plovdiv, Bulgaria, 4002
    • Study Site 12014
  • Plovdiv, Bulgaria, 4002
    • Study Site 12018
  • Sandanski, Bulgaria, 2800
    • Study Site 12017
  • Sofia, Bulgaria, 1233
    • Study Site 12003
  • Sofia, Bulgaria, 1309
    • Study Site 12001
  • Sofia, Bulgaria, 1407
    • Study Site 12004
  • Sofia, Bulgaria, 1407
    • Study Site 12012
  • Sofia, Bulgaria, 152
    • Study Site 12010
  • Sofia, Bulgaria, 1750
    • Study Site 12013
  • Varna, Bulgaria, 9010
    • Study Site 12011
  • Veliko Tarnovo, Bulgaria, 5000
    • Study Site 12002
  • Yambol, Bulgaria, 8600
    • Study Site 12007
• Canada
  • Quebec, Canada, G1V 4G5
    • Study Site - 13007
  • Alberta
    • Edmonton, Alberta, Canada, T5H 3V9
      • Study Site - 13003
    • Edmonton, Alberta, Canada, T6G 2B7
      • Study Site - 13002
  • British Columbia
    • Penticton, British Columbia, Canada, V2A 3G6
      • Study Site - 13017
    • Victoria, British Columbia, Canada, V8R 4R2
      • Study Site - 13012
  • Newfoundland and Labrador
    • St. Johns, Newfoundland and Labrador, Canada, A1B 3V6
      • Study Site - 13019
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Study Site - 13008
    • Newmarket, Ontario, Canada, L3Y 2P7
      • Study Site - 13010
  • Quebec
    • Montreal, Quebec, Canada, H2W 1T8
      • Study Site - 13014
• Czechia
  • Brno, Czechia, 625 00
    • Study Site 14010
  • Brno, Czechia, 656 91
    • Study Site 14006
  • Hradec Kralove, Czechia, 500 05
    • Study Site 14004
  • Jablonec nad Nisou, Czechia, 466 60
    • Study Site 14012
  • Jihlava, Czechia, 586 33
    • Study Site 14011
  • Kolin, Czechia, 280 00
    • Study Site 14016
  • Nachod, Czechia, 547 01
    • Study Site 14017
  • Ostrava, Czechia, 708 52
    • Study Site 14007
  • Pardubice, Czechia, 532 03
    • Study Site 14003
  • Praha 10, Czechia, 100 34
    • Study Site 14002
  • Praha 2, Czechia, 128 08
    • Study Site 14001
  • Praha 2, Czechia, 128 08
    • Study Site 14015
  • Praha 4 - Krc, Czechia, 140 59
    • Study Site 14008
  • Praha 5, Czechia, 150 06
    • Study Site 14009
  • Teplice, Czechia, 415 01
    • Study Site 14014
  • Usti nad Orlici, Czechia, 562 18
    • Study Site 14005
• Denmark
  • Alborg, Denmark, 9100
    • Study Site 15001
  • Esbjerg, Denmark, 6700
    • Study Site 15005
  • Hellerup, Denmark, 2900
    • Study Site 15002
  • Hvidovre, Denmark, 2650
    • Study Site 15004
  • Odense, Denmark, 5000
    • Study Site 15003
• France
  • Paris, France, 75013
    • Study Site - 25001
  • Gironde
    • Pessac, Gironde, France, 33604
      • Study Site - 25003
  • Haute Garonne
    • Toulouse cedex 3, Haute Garonne, France, 31076
      • Study Site - 25005
  • Loire Antlantique
    • Nantes cedex, Loire Antlantique, France, 44093
      • Study Site - 25008
  • Paris
    • Paris cedex 12, Paris, France, 75571
      • Study Site - 25002
  • Pyrenees Atlantiques
    • Pau, Pyrenees Atlantiques, France, 64046
      • Study Site - 25004
• Germany
  • Berlin, Germany, 10117
    • Study Site 17003
  • Berlin, Germany, 10967
    • Study Site 17009
  • Berlin, Germany, 12351
    • Study Site 17002
  • Hamburg, Germany, 20246
    • Study Site 17006
  • Baden Wuerttemberg
    • Freiburg, Baden Wuerttemberg, Germany, 79106
      • Study Site 17001
  • Berin
    • Berlin, Berin, Germany, 10249
      • Study Site 17005
  • Hessen
    • Franfurt, Hessen, Germany, 65929
      • Study Site 17014
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Study Site 17012
  • Nordrhein Westfalen
    • Luedenscheid, Nordrhein Westfalen, Germany, 58509
      • Study Site 17007
  • Rheinland Pfalz
    • Ludwigshafen, Rheinland Pfalz, Germany, 67063
      • Study Site 17010
    • Mainz, Rheinland Pfalz, Germany, 55131
      • Study Site 17011
• Hungary
  • Budapest, Hungary, 1023
    • Study Site 18008
  • Budapest, Hungary, 1122
    • Study Site 18001
  • Budapest, Hungary, 1134
    • Study Site 18005
  • Gyor, Hungary, 9024
    • Study Site 18002
  • Nyiregyhaza, Hungary, 4400
    • Study Site 18007
  • Pecs, Hungary, 7624
    • Study Site 18003
  • Szeged, Hungary, 6720
    • Study Site 18009
  • Szolnok, Hungary, 5000
    • Study Site 18006
• Israel
  • Ashkelon, Israel, 7830604
    • Study Site 19010
  • Beer Sheva, Israel, 8410101
    • Study Site 19006
  • Haifa, Israel, 3109601
    • Study Site 19005
  • Holon, Israel, 5822012
    • Study Site 19004
  • Jerusalem, Israel, 91120
    • Study Site 19003
  • Jerusalem, Israel, 9124001
    • Study Site 19007
  • Nahariya, Israel, 2210001
    • Study Site 19002
  • Ramat Gan, Israel, 5262000
    • Study Site 19009
  • Safed, Israel, 13100
    • Study Site 19008
• Italy
  • Benevento, Italy, 82100
    • Study Site 20009
  • Napoli, Italy, 80131
    • Study Site 20011
  • Rimini, Italy, 47923
    • Study Site 20007
  • Roma, Italy, 00189
    • Study Site 20012
  • Terni, Italy, 05100
    • Study Site 20001
  • Udine, Italy, 33100
    • Study Site 20006
  • Milano
    • Legnano, Milano, Italy, 20025
      • Study Site 20003
    • Magenta, Milano, Italy, 20013
      • Study Site 20002
    • Rozzano, Milano, Italy, 20089
      • Study Site 20008
• Netherlands
  • Alkmaar, Netherlands, 1815 JD
    • Study Site 21001
  • Amsterdam, Netherlands, 091 AC
    • Study Site 21006
  • Amsterdam, Netherlands, 1081 HV
    • Study Site 21013
  • Amsterdam, Netherlands, 1105 AZ
    • Study Site 21016
  • Ede, Netherlands, 6716 RP
    • Study Site 21004
  • Leeuwarden, Netherlands, 8934 AD
    • Study Site 21014
  • Nieuwegein, Netherlands, 3435 CM
    • Study Site 21003
  • Nijmegen, Netherlands, 6525 EC
    • Study Site 21008
  • Rotterdam, Netherlands, 3079 DZ
    • Study Site 21009
  • Sneek, Netherlands, 8601 ZK
    • Study Site 21010
  • Tilburg, Netherlands, 5042 AD
    • Study Site 21015
  • Venlo, Netherlands, 5912 BL
    • Study Site 21011
• Poland
  • Gdansk, Poland, 80-952
    • Study Site - 22015
  • Grodzisk Mazowiecki, Poland, 05-825
    • Study Site - 22010
  • Inowroclaw, Poland, 88-10
    • Study Site - 22012
  • Kielce, Poland, 25-736
    • Study Site 22009
  • Krakow, Poland, 31-202
    • Study Site - 22007
  • Lodz, Poland, 91-347
    • Study Site - 22014
  • Starogard Gdanski, Poland, 83-200
    • Study Site - 22013
  • Walbrzych, Poland, 58-309
    • Study Site - 22006
  • Warszawa, Poland, 01-211
    • Study Site - 22008
  • Wejherowo, Poland, 84-200
    • Study Site - 22016
  • Wroclaw, Poland, 50-981
    • Study Site - 22005
• Spain
  • Barcelona, Spain, 08003
    • Study Site - 23005
  • Barcelona, Spain, 08023
    • Study Site - 23002
  • Barcelona, Spain, 08036
    • Study Site - 23001
  • Madrid, Spain, 28007
    • Study Site - 23003
  • Madrid, Spain, 28034
    • Study Site - 23013
  • Madrid, Spain, 28040
    • Study Site - 23004
  • Malaga, Spain, 29010
    • Study Site - 23007
  • Tarragona, Spain, 43007
    • Study Site - 23009
  • Valencia, Spain, 46010
    • Study Site - 23011
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Study Site - 23010
  • La Coruna
    • A Coruna, La Coruna, Spain, 15006
      • Study Site - 23012
    • Santiago de Compostela, La Coruna, Spain, 15706
      • Study Site - 23006
• United Kingdom
  • Dunbartonshire
    • Clydebank, Dunbartonshire, United Kingdom, G81 1DY
      • Study Site - 24006
  • Essex
    • Basildon, Essex, United Kingdom, SS16 5NL
      • Study Site - 24004
    • Romford, Essex, United Kingdom, UM7 0AG
      • Study Site 24005
  • Greater London
    • London, Greater London, United Kingdom, E2 9JX
      • Study Site - 24003
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE3 9QP
      • Study Site - 24010
  • Tyne & Wear
    • Newcastle upon Tyne, Tyne & Wear, United Kingdom, NE7 7DN
      • Study Site - 24009
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Study Site 16101
    • Huntsville, Alabama, United States, 35801
      • Study Site 16078
  • California
    • Concord, California, United States, 94520
      • Study Site - 16168
    • Concord, California, United States, 94520
      • Study Site 16168
    • Sacramento, California, United States, 95819
      • Study Site 16147
    • Torrance, California, United States, 90502
      • Study Site 16022
  • Colorado
    • Littleton, Colorado, United States, 80120
      • Study Site 16130
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • Study Site 16170
    • Danbury, Connecticut, United States, 06810
      • Study Site 16135
  • Florida
    • Clearwater, Florida, United States, 33756
      • Study Site 16148
    • Jacksonville, Florida, United States, 32209
      • Study Site 16003
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Study Site 16144
  • Idaho
    • Boise, Idaho, United States, 83712
      • Study Site 16112
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Study Site 16060
  • Indiana
    • Elkhart, Indiana, United States, 46514
      • Study Site 16179
    • Indianapolis, Indiana, United States, 46290
      • Study Site 16102
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Study Site 16025
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Study Site 16088
    • Lexington, Kentucky, United States, 40536
      • Study Site 16004
    • Louisville, Kentucky, United States, 40202
      • Study Site 16016
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Study Site 16208
  • Maine
    • Auburn, Maine, United States, 04210
      • Study Site 16062
    • Bangor, Maine, United States, 04401
      • Study Site 16079
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Study Site 16031
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Study Site 16028
    • Petoskey, Michigan, United States, 49770
      • Study Site 16061
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Study Site 16211
    • Saint Paul, Minnesota, United States, 55102
      • Study Site 16234
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Study Site 16063
  • New York
    • Brooklyn, New York, United States, 11215
      • Study Site 16033
    • Buffalo, New York, United States, 14215
      • Study Site 16174
    • New York, New York, United States, 10029
      • Study Site 16213
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Study Site 16056
    • Elizabeth City, North Carolina, United States, 27909
      • Study Site 16201
    • High Point, North Carolina, United States, 27262
      • Study Site 16014
    • Winston-Salem, North Carolina, United States, 27157
      • Study Site 16024
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Study Site 16047
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Study Site 16026
    • Lancaster, Pennsylvania, United States, 17604
      • Study Site 16100
    • Philadelphia, Pennsylvania, United States, 19104
      • Study Site 16017
  • South Carolina
    • Greenwood, South Carolina, United States, 29646
      • Study Site 16039
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Study Site 16018
  • Tennessee
    • Greeneville, Tennessee, United States, 37745
      • Study Site 16202
  • Texas
    • Amarillo, Texas, United States, 79106
      • Study Site 16015
    • Dallas, Texas, United States, 75216
      • Study Site 16099
    • Wichita Falls, Texas, United States, 76301
      • Study Site 16241
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Study Site 16038
  • Wisconsin
    • Wausau, Wisconsin, United States, 54401
      • Study Site 16166

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CSL112 - low dose; CSL112 (low dose) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks.	Biological: 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.
Experimental: CSL112 - high dose; CSL112 (high dose) is to be administered as an IV infusion once weekly for 4 consecutive weeks.	Biological: 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.
Placebo Comparator: 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.	Biological: Placebo; 0.9% weight/volume sodium chloride solution (ie, normal saline)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	From baseline (before first infusion) to Day 29.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	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		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	apoA-I and PC are analytes of CSL112	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	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	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	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.	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.	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.	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.	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.	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.	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	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	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	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	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	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	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]	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]	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]	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]	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]	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]	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)	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)	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)	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)	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)	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)	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)	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)	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)	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)	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)	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)	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		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
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.	From the start of first infusion, up to approximately Day 382
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	The number of subjects who experience bleeding events as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al, 2011)	From the start of first infusion, up to approximately Day 112
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

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Dr. Denise D'Andrea, CSL Behring

Publications and helpful links

General Publications

• Zheng B, Duffy D, Tricoci P, Kastrissios H, Pfister M, Wright SD, Gille A, Tortorici MA. Pharmacometric analyses to characterize the effect of CSL112 on apolipoprotein A-I and cholesterol efflux capacity in acute myocardial infarction patients. Br J Clin Pharmacol. 2021 Jun;87(6):2558-2571. doi: 10.1111/bcp.14666. Epub 2020 Dec 23.
• Michael Gibson C, Korjian S, Tricoci P, Daaboul Y, Yee M, Jain P, Alexander JH, Steg PG, Lincoff AM, Kastelein JJ, Mehran R, D'Andrea DM, Deckelbaum LI, Merkely B, Zarebinski M, Ophuis TO, Harrington RA. Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Apolipoprotein A-I, After Acute Myocardial Infarction: The AEGIS-I Trial (ApoA-I Event Reducing in Ischemic Syndromes I). Circulation. 2016 Dec 13;134(24):1918-1930. doi: 10.1161/CIRCULATIONAHA.116.025687. Epub 2016 Nov 15.
• Gibson CM, Korjian S, Tricoci P, Daaboul Y, Alexander JH, Steg PG, Lincoff AM, Kastelein JJ, Mehran R, D'Andrea D, Merkely B, Zarebinski M, Ophius TO, Harrington RA. Rationale and design of Apo-I Event Reduction in Ischemic Syndromes I (AEGIS-I): A phase 2b, randomized, placebo-controlled, dose-ranging trial to investigate the safety and tolerability of CSL112, a reconstituted, infusible, human apoA-I, after acute myocardial infarction. Am Heart J. 2016 Oct;180:22-8. doi: 10.1016/j.ahj.2016.06.017. Epub 2016 Jul 5.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: March 31, 2014
• First Submitted That Met QC Criteria: April 6, 2014
• First Posted (Estimate): April 9, 2014

Study Record Updates

• Last Update Posted (Actual): March 15, 2021
• Last Update Submitted That Met QC Criteria: February 19, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction
• Other Study ID Numbers: CSLCT-HDL-12-77; 2013-003458-26 (EudraCT Number)