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

NCT ID: NCT02108262

Last Updated: 2021-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 1267 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-31
• Study Completion Date: 2016-03-31

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).

Conditions

Acute Myocardial Infarction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

CSL112 - low dose

CSL112 (low dose) is to be administered as an intravenous (IV) infusion once weekly for 4 consecutive weeks.

Group Type: EXPERIMENTAL

CSL112

Intervention Type: BIOLOGICAL

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

CSL112 - high dose

CSL112 (high dose) is to be administered as an IV infusion once weekly for 4 consecutive weeks.

Group Type: EXPERIMENTAL

CSL112

Intervention Type: BIOLOGICAL

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

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

Interventions

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.

Intervention Type: BIOLOGICAL

Placebo

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CSL Behring

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dr. Denise D'Andrea

Role: STUDY_DIRECTOR

CSL Behring

Locations

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

Study Site 16003

Jacksonville, Florida, United States

Study Site 16144

Atlanta, Georgia, United States

Study Site 16112

Boise, Idaho, United States

Study Site 16060

Evanston, Illinois, United States

Study Site 16179

Elkhart, Indiana, United States

Study Site 16102

Indianapolis, Indiana, United States

Study Site 16025

West Des Moines, Iowa, United States

Study Site 16088

Lexington, Kentucky, United States

Study Site 16004

Lexington, Kentucky, United States

Study Site 16016

Louisville, Kentucky, United States

Study Site 16208

Alexandria, Louisiana, United States

Study Site 16062

Auburn, Maine, United States

Study Site 16079

Bangor, Maine, United States

Study Site 16031

Baltimore, Maryland, United States

Study Site 16028

Detroit, Michigan, United States

Study Site 16061

Petoskey, Michigan, United States

Study Site 16211

Minneapolis, Minnesota, United States

Study Site 16234

Saint Paul, Minnesota, United States

Study Site 16063

Tupelo, Mississippi, United States

Study Site 16033

Brooklyn, New York, United States

Study Site 16174

Buffalo, New York, United States

Study Site 16213

New York, New York, United States

Study Site 16056

Durham, North Carolina, United States

Study Site 16201

Elizabeth City, North Carolina, United States

Study Site 16014

High Point, North Carolina, United States

Study Site 16024

Winston-Salem, North Carolina, United States

Study Site 16047

Cincinnati, Ohio, United States

Study Site 16026

Hershey, Pennsylvania, United States

Study Site 16100

Lancaster, Pennsylvania, United States

Study Site 16017

Philadelphia, Pennsylvania, United States

Study Site 16039

Greenwood, South Carolina, United States

Study Site 16018

Rapid City, South Dakota, United States

Study Site 16202

Greeneville, Tennessee, United States

Study Site 16015

Amarillo, Texas, United States

Study Site 16099

Dallas, Texas, United States

Study Site 16241

Wichita Falls, Texas, United States

Study Site 16038

Richmond, Virginia, United States

Study Site 16166

Wausau, Wisconsin, United States

Study Site 10002

Herston, Queensland, Australia

Study Site 10005

Adelaide, South Australia, Australia

Study Site 10012

Woodville South, South Australia, Australia

Study Site 10006

Epping, Victoria, Australia

Study Site 10007

Geelong, Victoria, Australia

Study Site 11004

Innsbruck, , Austria

Study Site 11002

Vienna, , Austria

Study Site 11001

Vienna, , Austria

Study Site 12005

Blagoevgrad, , Bulgaria

Study Site 12008

Burgas, , Bulgaria

Study Site 12006

Dobrich, , Bulgaria

Study Site 12021

Haskovo, , Bulgaria

Study Site 12009

Pazardzhik, , Bulgaria

Study Site 12019

Pazardzhik, , Bulgaria

Study Site 12016

Pleven, , Bulgaria

Study Site 12014

Plovdiv, , Bulgaria

Study Site 12018

Plovdiv, , Bulgaria

Study Site 12017

Sandanski, , Bulgaria

Study Site 12003

Sofia, , Bulgaria

Study Site 12001

Sofia, , Bulgaria

Study Site 12004

Sofia, , Bulgaria

Study Site 12012

Sofia, , Bulgaria

Study Site 12010

Sofia, , Bulgaria

Study Site 12013

Sofia, , Bulgaria

Study Site 12011

Varna, , Bulgaria

Study Site 12002

Veliko Tarnovo, , Bulgaria

Study Site 12007

Yambol, , Bulgaria

Study Site - 13003

Edmonton, Alberta, Canada

Study Site - 13002

Edmonton, Alberta, Canada

Study Site - 13017

Penticton, British Columbia, Canada

Study Site - 13012

Victoria, British Columbia, Canada

Study Site - 13019

St. John's, Newfoundland and Labrador, Canada

Study Site - 13008

London, Ontario, Canada

Study Site - 13010

Newmarket, Ontario, Canada

Study Site - 13014

Montreal, Quebec, Canada

Study Site - 13007

Québec, , Canada

Study Site 14010

Brno, , Czechia

Study Site 14006

Brno, , Czechia

Study Site 14004

Hradec Králové, , Czechia

Study Site 14012

Jablonec nad Nisou, , Czechia

Study Site 14011

Jihlava, , Czechia

Study Site 14016

Kolín, , Czechia

Study Site 14017

Náchod, , Czechia

Study Site 14007

Ostrava, , Czechia

Study Site 14003

Pardubice, , Czechia

Study Site 14002

Prague, , Czechia

Study Site 14001

Prague, , Czechia

Study Site 14015

Prague, , Czechia

Study Site 14009

Prague, , Czechia

Study Site 14008

Praha 4 - Krc, , Czechia

Study Site 14014

Teplice, , Czechia

Study Site 14005

Ústí nad Orlicí, , Czechia

Study Site 15001

Aalborg, , Denmark

Study Site 15005

Esbjerg, , Denmark

Study Site 15002

Hellerup, , Denmark

Study Site 15004

Hvidovre, , Denmark

Study Site 15003

Odense, , Denmark

Study Site - 25003

Pessac, Gironde, France

Study Site - 25005

Toulouse, Haute Garonne, France

Study Site - 25008

Nantes, Loire Antlantique, France

Study Site - 25002

Paris, Paris, France

Study Site - 25004

Pau, Pyrenees Atlantiques, France

Study Site - 25001

Paris, , France

Study Site 17001

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Study Site 17005

Berlin, Berin, Germany

Study Site 17014

Franfurt, Hesse, Germany

Study Site 17012

Hanover, Lower Saxony, Germany

Study Site 17007

Lüdenscheid, North Rhine-Westphalia, Germany

Study Site 17010

Ludwigshafen am Rhein, Rhineland-Palatinate, Germany

Study Site 17011

Mainz, Rhineland-Palatinate, Germany

Study Site 17003

Berlin, , Germany

Study Site 17009

Berlin, , Germany

Study Site 17002

Berlin, , Germany

Study Site 17006

Hamburg, , Germany

Study Site 18008

Budapest, , Hungary

Study Site 18001

Budapest, , Hungary

Study Site 18005

Budapest, , Hungary

Study Site 18002

Győr, , Hungary

Study Site 18007

Nyíregyháza, , Hungary

Study Site 18003

Pécs, , Hungary

Study Site 18009

Szeged, , Hungary

Study Site 18006

Szolnok, , Hungary

Study Site 19010

Ashkelon, , Israel

Study Site 19006

Beersheba, , Israel

Study Site 19005

Haifa, , Israel

Study Site 19004

Holon, , Israel

Study Site 19003

Jerusalem, , Israel

Study Site 19007

Jerusalem, , Israel

Study Site 19002

Nahariya, , Israel

Study Site 19009

Ramat Gan, , Israel

Study Site 19008

Safed, , Israel

Study Site 20003

Legnano, Milano, Italy

Study Site 20002

Magenta, Milano, Italy

Study Site 20008

Rozzano, Milano, Italy

Study Site 20009

Benevento, , Italy

Study Site 20011

Napoli, , Italy

Study Site 20007

Rimini, , Italy

Study Site 20012

Roma, , Italy

Study Site 20001

Terni, , Italy

Study Site 20006

Udine, , Italy

Study Site 21001

Alkmaar, , Netherlands

Study Site 21006

Amsterdam, , Netherlands

Study Site 21013

Amsterdam, , Netherlands

Study Site 21016

Amsterdam, , Netherlands

Study Site 21004

Ede, , Netherlands

Study Site 21014

Leeuwarden, , Netherlands

Study Site 21003

Nieuwegein, , Netherlands

Study Site 21008

Nijmegen, , Netherlands

Study Site 21009

Rotterdam, , Netherlands

Study Site 21010

Sneek, , Netherlands

Study Site 21015

Tilburg, , Netherlands

Study Site 21011

Venlo, , Netherlands

Study Site - 22015

Gdansk, , Poland

Study Site - 22010

Grodzisk Mazowiecki, , Poland

Study Site - 22012

Inowrocław, , Poland

Study Site 22009

Kielce, , Poland

Study Site - 22007

Krakow, , Poland

Study Site - 22014

Lodz, , Poland

Study Site - 22013

Starogard Gdański, , Poland

Study Site - 22008

Warsaw, , Poland

Study Site - 22006

Wałbrzych, , Poland

Study Site - 22016

Wejherowo, , Poland

Study Site - 22005

Wroclaw, , Poland

Study Site - 23010

L'Hospitalet de Llobregat, Barcelona, Spain

Study Site - 23012

A Coruña, La Coruna, Spain

Study Site - 23006

Santiago de Compostela, La Coruna, Spain

Study Site - 23005

Barcelona, , Spain

Study Site - 23002

Barcelona, , Spain

Study Site - 23001

Barcelona, , Spain

Study Site - 23003

Madrid, , Spain

Study Site - 23013

Madrid, , Spain

Study Site - 23004

Madrid, , Spain

Study Site - 23007

Málaga, , Spain

Study Site - 23009

Tarragona, , Spain

Study Site - 23011

Valencia, , Spain

Study Site - 24006

Clydebank, Dunbartonshire, United Kingdom

Study Site - 24004

Basildon, Essex, United Kingdom

Study Site 24005

Romford, Essex, United Kingdom

Study Site - 24003

London, Greater London, United Kingdom

Study Site - 24010

Leicester, Leicestershire, United Kingdom

Study Site - 24009

Newcastle upon Tyne, Tyne & Wear, United Kingdom

Countries

United States; Australia; Austria; Bulgaria; Canada; Czechia; Denmark; France; Germany; Hungary; Israel; Italy; Netherlands; Poland; Spain; United Kingdom

References

Didichenko SA, Velkoska E, Navdaev AV, Greene BH, Lorkowski SW, Duffy D, Mears SJ, Wright SD, Gibson CM, Smith JD, Kingwell BA. CSL112 Infusion Rapidly Increases APOA1 Exchange Rate via Specific Serum Amyloid-Poor HDL Subpopulations When Administered to Patients Post-Myocardial Infarction. Arterioscler Thromb Vasc Biol. 2023 Jun;43(6):855-869. doi: 10.1161/ATVBAHA.122.318243. Epub 2023 Mar 30.

Reference Type: DERIVED

PMID: 36994730 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33217027 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27881559 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27659879 (View on PubMed)

Other Identifiers

2013-003458-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CSLCT-HDL-12-77

Identifier Type: -

Identifier Source: org_study_id