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

NCT02108262 | Completed Phase 2 Results DMC

• 2 other identifiers: CSLCT-HDL-12-772013-003458-26
• Study Type: interventional
• Target: 1,267
• Locations: 15 countries
• Sites: 184

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (61)

• 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

• 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

• 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

• 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

Study Arms (3)

CSL112 - low dose

EXPERIMENTAL

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

Biological: CSL112

CSL112 - high dose

EXPERIMENTAL

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

Biological: CSL112

Placebo

PLACEBO COMPARATOR

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

Interventions

CSL112 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 - low dose

Placebo BIOLOGICAL

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (189)

Study Site 16101

Birmingham, Alabama, 35211, United States

Location

Study Site 16078

Huntsville, Alabama, 35801, United States

Location

Study Site - 16168

Concord, California, 94520, United States

Location

Study Site 16168

Concord, California, 94520, United States

Location

Study Site 16147

Sacramento, California, 95819, United States

Location

Study Site 16022

Torrance, California, 90502, United States

Location

Study Site 16130

Littleton, Colorado, 80120, United States

Location

Study Site 16170

Bridgeport, Connecticut, 06606, United States

Location

Study Site 16135

Danbury, Connecticut, 06810, United States

Location

Study Site 16148

Clearwater, Florida, 33756, United States

Location

Study Site 16003

Jacksonville, Florida, 32209, United States

Location

Study Site 16144

Atlanta, Georgia, 30322, United States

Location

Study Site 16112

Boise, Idaho, 83712, United States

Location

Study Site 16060

Evanston, Illinois, 60201, United States

Location

Study Site 16179

Elkhart, Indiana, 46514, United States

Location

Study Site 16102

Indianapolis, Indiana, 46290, United States

Location

Study Site 16025

West Des Moines, Iowa, 50266, United States

Location

Study Site 16088

Lexington, Kentucky, 40504, United States

Location

Study Site 16004

Lexington, Kentucky, 40536, United States

Location

Study Site 16016

Louisville, Kentucky, 40202, United States

Location

Study Site 16208

Alexandria, Louisiana, 71301, United States

Location

Study Site 16062

Auburn, Maine, 04210, United States

Location

Study Site 16079

Bangor, Maine, 04401, United States

Location

Study Site 16031

Baltimore, Maryland, 21215, United States

Location

Study Site 16028

Detroit, Michigan, 48202, United States

Location

Study Site 16061

Petoskey, Michigan, 49770, United States

Location

Study Site 16211

Minneapolis, Minnesota, 55407, United States

Location

Study Site 16234

Saint Paul, Minnesota, 55102, United States

Location

Study Site 16063

Tupelo, Mississippi, 38801, United States

Location

Study Site 16033

Brooklyn, New York, 11215, United States

Location

Study Site 16174

Buffalo, New York, 14215, United States

Location

Study Site 16213

New York, New York, 10029, United States

Location

Study Site 16056

Durham, North Carolina, 27705, United States

Location

Study Site 16201

Elizabeth City, North Carolina, 27909, United States

Location

Study Site 16014

High Point, North Carolina, 27262, United States

Location

Study Site 16024

Winston-Salem, North Carolina, 27157, United States

Location

Study Site 16047

Cincinnati, Ohio, 45219, United States

Location

Study Site 16026

Hershey, Pennsylvania, 17033, United States

Location

Study Site 16100

Lancaster, Pennsylvania, 17604, United States

Location

Study Site 16017

Philadelphia, Pennsylvania, 19104, United States

Location

Study Site 16039

Greenwood, South Carolina, 29646, United States

Location

Study Site 16018

Rapid City, South Dakota, 57701, United States

Location

Study Site 16202

Greeneville, Tennessee, 37745, United States

Location

Study Site 16015

Amarillo, Texas, 79106, United States

Location

Study Site 16099

Dallas, Texas, 75216, United States

Location

Study Site 16241

Wichita Falls, Texas, 76301, United States

Location

Study Site 16038

Richmond, Virginia, 23298, United States

Location

Study Site 16166

Wausau, Wisconsin, 54401, United States

Location

Study Site 10002

Herston, Queensland, 4029, Australia

Location

Study Site 10005

Adelaide, South Australia, 5000, Australia

Location

Study Site 10012

Woodville South, South Australia, 5011, Australia

Location

Study Site 10006

Epping, Victoria, 3076, Australia

Location

Study Site 10007

Geelong, Victoria, 3220, Australia

Location

Study Site 11004

Innsbruck, 6020, Austria

Location

Study Site 11002

Vienna, 1090, Austria

Location

Study Site 11001

Vienna, 1160, Austria

Location

Study Site 12005

Blagoevgrad, 2700, Bulgaria

Location

Study Site 12008

Burgas, 8000, Bulgaria

Location

Study Site 12006

Dobrich, 9300, Bulgaria

Location

Study Site 12021

Haskovo, 6300, Bulgaria

Location

Study Site 12009

Pazardzhik, 4400, Bulgaria

Location

Study Site 12019

Pazardzhik, 4400, Bulgaria

Location

Study Site 12016

Pleven, 5800, Bulgaria

Location

Study Site 12014

Plovdiv, 4002, Bulgaria

Location

Study Site 12018

Plovdiv, 4002, Bulgaria

Location

Study Site 12017

Sandanski, 2800, Bulgaria

Location

Study Site 12003

Sofia, 1233, Bulgaria

Location

Study Site 12001

Sofia, 1309, Bulgaria

Location

Study Site 12004

Sofia, 1407, Bulgaria

Location

Study Site 12012

Sofia, 1407, Bulgaria

Location

Study Site 12010

Sofia, 152, Bulgaria

Location

Study Site 12013

Sofia, 1750, Bulgaria

Location

Study Site 12011

Varna, 9010, Bulgaria

Location

Study Site 12002

Veliko Tarnovo, 5000, Bulgaria

Location

Study Site 12007

Yambol, 8600, Bulgaria

Location

Study Site - 13003

Edmonton, Alberta, T5H 3V9, Canada

Location

Study Site - 13002

Edmonton, Alberta, T6G 2B7, Canada

Location

Study Site - 13017

Penticton, British Columbia, V2A 3G6, Canada

Location

Study Site - 13012

Victoria, British Columbia, V8R 4R2, Canada

Location

Study Site - 13019

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

Study Site - 13008

London, Ontario, N6A 5A5, Canada

Location

Study Site - 13010

Newmarket, Ontario, L3Y 2P7, Canada

Location

Study Site - 13014

Montreal, Quebec, H2W 1T8, Canada

Location

Study Site - 13007

Québec, G1V 4G5, Canada

Location

Study Site 14010

Brno, 625 00, Czechia

Location

Study Site 14006

Brno, 656 91, Czechia

Location

Study Site 14004

Hradec Králové, 500 05, Czechia

Location

Study Site 14012

Jablonec nad Nisou, 466 60, Czechia

Location

Study Site 14011

Jihlava, 586 33, Czechia

Location

Study Site 14016

Kolín, 280 00, Czechia

Location

Study Site 14017

Náchod, 547 01, Czechia

Location

Study Site 14007

Ostrava, 708 52, Czechia

Location

Study Site 14003

Pardubice, 532 03, Czechia

Location

Study Site 14002

Prague, 100 34, Czechia

Location

Study Site 14001

Prague, 128 08, Czechia

Location

Study Site 14015

Prague, 128 08, Czechia

Location

Study Site 14009

Prague, 150 06, Czechia

Location

Study Site 14008

Praha 4 - Krc, 140 59, Czechia

Location

Study Site 14014

Teplice, 415 01, Czechia

Location

Study Site 14005

Ústí nad Orlicí, 562 18, Czechia

Location

Study Site 15001

Aalborg, 9100, Denmark

Location

Study Site 15005

Esbjerg, 6700, Denmark

Location

Study Site 15002

Hellerup, 2900, Denmark

Location

Study Site 15004

Hvidovre, 2650, Denmark

Location

Study Site 15003

Odense, 5000, Denmark

Location

Study Site - 25003

Pessac, Gironde, 33604, France

Location

Study Site - 25005

Toulouse, Haute Garonne, 31076, France

Location

Study Site - 25008

Nantes, Loire Antlantique, 44093, France

Location

Study Site - 25002

Paris, Paris, 75571, France

Location

Study Site - 25004

Pau, Pyrenees Atlantiques, 64046, France

Location

Study Site - 25001

Paris, 75013, France

Location

Study Site 17001

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Study Site 17005

Berlin, Berin, 10249, Germany

Location

Study Site 17014

Franfurt, Hesse, 65929, Germany

Location

Study Site 17012

Hanover, Lower Saxony, 30625, Germany

Location

Study Site 17007

Lüdenscheid, North Rhine-Westphalia, 58509, Germany

Location

Study Site 17010

Ludwigshafen am Rhein, Rhineland-Palatinate, 67063, Germany

Location

Study Site 17011

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Study Site 17003

Berlin, 10117, Germany

Location

Study Site 17009

Berlin, 10967, Germany

Location

Study Site 17002

Berlin, 12351, Germany

Location

Study Site 17006

Hamburg, 20246, Germany

Location

Study Site 18008

Budapest, 1023, Hungary

Location

Study Site 18001

Budapest, 1122, Hungary

Location

Study Site 18005

Budapest, 1134, Hungary

Location

Study Site 18002

Győr, 9024, Hungary

Location

Study Site 18007

Nyíregyháza, 4400, Hungary

Location

Study Site 18003

Pécs, 7624, Hungary

Location

Study Site 18009

Szeged, 6720, Hungary

Location

Study Site 18006

Szolnok, 5000, Hungary

Location

Study Site 19010

Ashkelon, 7830604, Israel

Location

Study Site 19006

Beersheba, 8410101, Israel

Location

Study Site 19005

Haifa, 3109601, Israel

Location

Study Site 19004

Holon, 5822012, Israel

Location

Study Site 19003

Jerusalem, 91120, Israel

Location

Study Site 19007

Jerusalem, 9124001, Israel

Location

Study Site 19002

Nahariya, 2210001, Israel

Location

Study Site 19009

Ramat Gan, 5262000, Israel

Location

Study Site 19008

Safed, 13100, Israel

Location

Study Site 20003

Legnano, Milano, 20025, Italy

Location

Study Site 20002

Magenta, Milano, 20013, Italy

Location

Study Site 20008

Rozzano, Milano, 20089, Italy

Location

Study Site 20009

Benevento, 82100, Italy

Location

Study Site 20011

Napoli, 80131, Italy

Location

Study Site 20007

Rimini, 47923, Italy

Location

Study Site 20012

Roma, 00189, Italy

Location

Study Site 20001

Terni, 05100, Italy

Location

Study Site 20006

Udine, 33100, Italy

Location

Study Site 21001

Alkmaar, 1815 JD, Netherlands

Location

Study Site 21006

Amsterdam, 091 AC, Netherlands

Location

Study Site 21013

Amsterdam, 1081 HV, Netherlands

Location

Study Site 21016

Amsterdam, 1105 AZ, Netherlands

Location

Study Site 21004

Ede, 6716 RP, Netherlands

Location

Study Site 21014

Leeuwarden, 8934 AD, Netherlands

Location

Study Site 21003

Nieuwegein, 3435 CM, Netherlands

Location

Study Site 21008

Nijmegen, 6525 EC, Netherlands

Location

Study Site 21009

Rotterdam, 3079 DZ, Netherlands

Location

Study Site 21010

Sneek, 8601 ZK, Netherlands

Location

Study Site 21015

Tilburg, 5042 AD, Netherlands

Location

Study Site 21011

Venlo, 5912 BL, Netherlands

Location

Study Site - 22015

Gdansk, 80-952, Poland

Location

Study Site - 22010

Grodzisk Mazowiecki, 05-825, Poland

Location

Study Site - 22012

Inowrocław, 88-10, Poland

Location

Study Site 22009

Kielce, 25-736, Poland

Location

Study Site - 22007

Krakow, 31-202, Poland

Location

Study Site - 22014

Lodz, 91-347, Poland

Location

Study Site - 22013

Starogard Gdański, 83-200, Poland

Location

Study Site - 22008

Warsaw, 01-211, Poland

Location

Study Site - 22006

Wałbrzych, 58-309, Poland

Location

Study Site - 22016

Wejherowo, 84-200, Poland

Location

Study Site - 22005

Wroclaw, 50-981, Poland

Location

Study Site - 23010

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Study Site - 23012

A Coruña, La Coruna, 15006, Spain

Location

Study Site - 23006

Santiago de Compostela, La Coruna, 15706, Spain

Location

Study Site - 23005

Barcelona, 08003, Spain

Location

Study Site - 23002

Barcelona, 08023, Spain

Location

Study Site - 23001

Barcelona, 08036, Spain

Location

Study Site - 23003

Madrid, 28007, Spain

Location

Study Site - 23013

Madrid, 28034, Spain

Location

Study Site - 23004

Madrid, 28040, Spain

Location

Study Site - 23007

Málaga, 29010, Spain

Location

Study Site - 23009

Tarragona, 43007, Spain

Location

Study Site - 23011

Valencia, 46010, Spain

Location

Study Site - 24006

Clydebank, Dunbartonshire, G81 1DY, United Kingdom

Location

Study Site - 24004

Basildon, Essex, SS16 5NL, United Kingdom

Location

Study Site 24005

Romford, Essex, UM7 0AG, United Kingdom

Location

Study Site - 24003

London, Greater London, E2 9JX, United Kingdom

Location

Study Site - 24010

Leicester, Leicestershire, LE3 9QP, United Kingdom

Location

Study Site - 24009

Newcastle upon Tyne, Tyne & Wear, NE7 7DN, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 36994730 DERIVED

• 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.

  PMID: 33217027 DERIVED

• 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.

  PMID: 27881559 DERIVED

• 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.

  PMID: 27659879 DERIVED

MeSH Terms

Interventions

CSL112

Results Point of Contact

• Title: Trial Registration Coordinator
• Organization: CSLBehring

clinicaltrials@cslbehring.com

610-878-4000

Study Officials

• Dr. Denise D'Andrea

  CSL Behring

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2014
• First Posted: April 9, 2014
• Study Start: August 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: March 1, 2016
• Last Updated: March 15, 2021
• Results First Posted: March 15, 2021

Record last verified: 2021-02

Locations

CZ (16); NL (12); ES (12); GB (6); AU (3); US (48); FR (6); DE (11); CA (9); BU (19); HU (8); IT (9); DK (5); IL (9); PL (11)