Effect of CER-001 on Atherosclerosis in Acute Coronary Syndrome (ACS) Patients - Efficacy and Safety: The CHI SQUARE Trial

NCT ID: NCT01201837

Last Updated: 2014-03-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

507 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-03-31

Study Completion Date

2013-03-31

Brief Summary

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Cardiovascular disease remains the most pressing healthcare issue for developed countries and is becoming so for developing countries. There are a number of chronic therapies available for long-term management of risk. Short term therapies for subjects with an acute event, such as an episode of acute coronary syndrome (ACS), are focused on reperfusion and removing thrombus but most subsequent events are caused by atherosclerotic plaque rupture at a different site. There are no approved therapies that can rapidly reduce the burden of unstable, inflamed plaque in the overall coronary vascular bed. HDL has multiple actions that could lead to atherosclerotic plaque stabilization, such as rapid removal of large quantities of cholesterol from the vasculature, improvement in endothelial function, protection against oxidative damage and reduction in inflammation. This study will assess the effects of CER-001, an ApoA-I-based HDL mimetic, on indices of atherosclerotic plaque progression and regression as assessed by intravascular ultrasound (IVUS) measurements in patients with (ACS).

Detailed Description

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Conditions

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Acute Coronary Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Weekly injection

Low Dose

CER-001 Low Dose

Group Type EXPERIMENTAL

CER-001

Intervention Type DRUG

Weekly injection

Mid Dose

CER-001 Mid Dose

Group Type EXPERIMENTAL

CER-001

Intervention Type DRUG

Weekly injection

High Dose

CER-001 High Dose

Group Type EXPERIMENTAL

CER-001

Intervention Type DRUG

Weekly injection

Interventions

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Placebo

Weekly injection

Intervention Type DRUG

CER-001

Weekly injection

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Male or female less than 75 years of age
* Acute coronary syndrome (acute chest pain and a diagnosis of ST segment elevation myocardial infarction, non-ST elevation myocardial infarction or unstable angina)
* Angiographic evidence of coronary artery disease with suitable "target" coronary artery for IVUS evaluation

Exclusion Criteria

* Females of child-bearing potential
* Weight \>120 kg
* Angiographic evidence of \>50% stenosis of the left main artery
* Uncontrolled diabetes (HbA1C\>10%)
* Hypertriglyceridemia (\>500 mg/dL)
* Congestive heart failure (NYHA class III or IV)
* Ejection fraction \<35%
* Uncontrolled hypertension (SBP \>180 mm Hg)
* Known major hematologic, renal, hepatic, metabolic, gastrointestinal or endocrine dysfunction
Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cerenis Therapeutics, SA

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean-Claude Tardif, MD

Role: PRINCIPAL_INVESTIGATOR

Montreal Heart Institute

Locations

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Heart Center Research LLC

Huntsville, Alabama, United States

Site Status

Mayo Clinic - Arizona

Phoenix, Arizona, United States

Site Status

VA San Diego Health Care Center

San Diego, California, United States

Site Status

Palm Beach Heart Institute, LLC - Zasa Clinical Research

Boynton Beach, Florida, United States

Site Status

Heart and Vascular Institute of Florida

Clearwater, Florida, United States

Site Status

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Site Status

Saint Joseph Research Institute

Atlanta, Georgia, United States

Site Status

The Care Group, LLC

Indianapolis, Indiana, United States

Site Status

Suburban Hospital

Bethesda, Maryland, United States

Site Status

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

Detroit Medical Center (DMC) Cardiovascular Institute

Detroit, Michigan, United States

Site Status

Cardiac and Vascular Research Center of Northern Michigan

Petoskey, Michigan, United States

Site Status

Alegent Research Center

Omaha, Nebraska, United States

Site Status

Buffalo Heart Group

Buffalo, New York, United States

Site Status

Buffalo Cardiology & Pulmonary Associates

Williamsville, New York, United States

Site Status

University of North Carolina Medical Center

Chapel Hill, North Carolina, United States

Site Status

LeBauer Cardiovascular Research Foundation

Greensboro, North Carolina, United States

Site Status

Sanford Heart Center

Fargo, North Dakota, United States

Site Status

South Oklahoma Heart Research

Oklahoma City, Oklahoma, United States

Site Status

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

Site Status

Sanford Research / USD

Sioux Falls, South Dakota, United States

Site Status

Baptist Memorial Hospital

Memphis, Tennessee, United States

Site Status

Dallas VA Medical Center

Dallas, Texas, United States

Site Status

MultiCare Health System Research Institute / Cardiac Study Center

Tacoma, Washington, United States

Site Status

Foothills Medical Centre

Calgary, Alberta, Canada

Site Status

Victoria Heart Institute Foundation

Victoria, British Columbia, Canada

Site Status

St. John Health Center

St. John's, Newfoundland and Labrador, Canada

Site Status

London Health Sciences Center

London, Ontario, Canada

Site Status

St. Michael's Hospital

Toronto, Ontario, Canada

Site Status

Centre de Santé et de Services Sociaux de Laval

Laval, Quebec, Canada

Site Status

Montreal Heart Institute

Montreal, Quebec, Canada

Site Status

Montreal General Hospital Research Institute

Montreal, Quebec, Canada

Site Status

Institut Universitaire de Cardiologie et Pneumologie de Québec (IUCPQ)

Québec, Quebec, Canada

Site Status

CSSS du Nord de Lanaudière

Saint-Charles-Borromée, Quebec, Canada

Site Status

Centre Hospitalier Régional de Trois-Rivières

Trois-Rivières, Quebec, Canada

Site Status

Hôpital Cardiologique du Haut-Lévesque

Bordeaux, Pessac Cedex, France

Site Status

Clinique Pasteur

Toulouse, , France

Site Status

Centre Hospitalier Universitaire de Toulouse Rangueil

Toulouse, , France

Site Status

Onze Lieve Vrouwe Gasthius

Amsterdam, AC, Netherlands

Site Status

Medisch Centrum Leeuwarden

Leeuwarden, AD, Netherlands

Site Status

Medisch Centrum Alkmaar

Alkmaar, Amsterdam, Netherlands

Site Status

Academic Medical Center

Amsterdam, AZ, Netherlands

Site Status

St. Antonius Ziekenhuis Nieuwegein

Nieuwegein, CM, Netherlands

Site Status

Maassstadziekenhuis Cardiology Research

Rotterdam, DZ, Netherlands

Site Status

Catharina Ziekenhuis Eindhoven

Eindhoven, EJ, Netherlands

Site Status

Medisch Spectrum Twente

Enschede, ER, Netherlands

Site Status

Canisius Wilhelmina Ziekenhuis

Nijmegen, SZ, Netherlands

Site Status

Countries

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United States Canada France Netherlands

References

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Nanjee MN, Doran JE, Lerch PG, Miller NE. Acute effects of intravenous infusion of ApoA1/phosphatidylcholine discs on plasma lipoproteins in humans. Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):979-89. doi: 10.1161/01.atv.19.4.979.

Reference Type BACKGROUND
PMID: 10195926 (View on PubMed)

Eriksson M, Carlson LA, Miettinen TA, Angelin B. Stimulation of fecal steroid excretion after infusion of recombinant proapolipoprotein A-I. Potential reverse cholesterol transport in humans. Circulation. 1999 Aug 10;100(6):594-8. doi: 10.1161/01.cir.100.6.594.

Reference Type BACKGROUND
PMID: 10441095 (View on PubMed)

Spieker LE, Sudano I, Hurlimann D, Lerch PG, Lang MG, Binggeli C, Corti R, Ruschitzka F, Luscher TF, Noll G. High-density lipoprotein restores endothelial function in hypercholesterolemic men. Circulation. 2002 Mar 26;105(12):1399-402. doi: 10.1161/01.cir.0000013424.28206.8f.

Reference Type BACKGROUND
PMID: 11914243 (View on PubMed)

Nieuwdorp M, Vergeer M, Bisoendial RJ, op 't Roodt J, Levels H, Birjmohun RS, Kuivenhoven JA, Basser R, Rabelink TJ, Kastelein JJ, Stroes ES. Reconstituted HDL infusion restores endothelial function in patients with type 2 diabetes mellitus. Diabetologia. 2008 Jun;51(6):1081-4. doi: 10.1007/s00125-008-0975-2. Epub 2008 Apr 4. No abstract available.

Reference Type BACKGROUND
PMID: 18389214 (View on PubMed)

Drew BG, Duffy SJ, Formosa MF, Natoli AK, Henstridge DC, Penfold SA, Thomas WG, Mukhamedova N, de Courten B, Forbes JM, Yap FY, Kaye DM, van Hall G, Febbraio MA, Kemp BE, Sviridov D, Steinberg GR, Kingwell BA. High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus. Circulation. 2009 Apr 21;119(15):2103-11. doi: 10.1161/CIRCULATIONAHA.108.843219. Epub 2009 Apr 6.

Reference Type BACKGROUND
PMID: 19349317 (View on PubMed)

Shaw JA, Bobik A, Murphy A, Kanellakis P, Blombery P, Mukhamedova N, Woollard K, Lyon S, Sviridov D, Dart AM. Infusion of reconstituted high-density lipoprotein leads to acute changes in human atherosclerotic plaque. Circ Res. 2008 Nov 7;103(10):1084-91. doi: 10.1161/CIRCRESAHA.108.182063. Epub 2008 Oct 2.

Reference Type BACKGROUND
PMID: 18832751 (View on PubMed)

Waksman R, Torguson R, Kent KM, Pichard AD, Suddath WO, Satler LF, Martin BD, Perlman TJ, Maltais JA, Weissman NJ, Fitzgerald PJ, Brewer HB Jr. A first-in-man, randomized, placebo-controlled study to evaluate the safety and feasibility of autologous delipidated high-density lipoprotein plasma infusions in patients with acute coronary syndrome. J Am Coll Cardiol. 2010 Jun 15;55(24):2727-35. doi: 10.1016/j.jacc.2009.12.067.

Reference Type BACKGROUND
PMID: 20538165 (View on PubMed)

Tardif JC, Gregoire J, L'Allier PL, Ibrahim R, Lesperance J, Heinonen TM, Kouz S, Berry C, Basser R, Lavoie MA, Guertin MC, Rodes-Cabau J; Effect of rHDL on Atherosclerosis-Safety and Efficacy (ERASE) Investigators. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA. 2007 Apr 18;297(15):1675-82. doi: 10.1001/jama.297.15.jpc70004. Epub 2007 Mar 26.

Reference Type BACKGROUND
PMID: 17387133 (View on PubMed)

Nissen SE, Tsunoda T, Tuzcu EM, Schoenhagen P, Cooper CJ, Yasin M, Eaton GM, Lauer MA, Sheldon WS, Grines CL, Halpern S, Crowe T, Blankenship JC, Kerensky R. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA. 2003 Nov 5;290(17):2292-300. doi: 10.1001/jama.290.17.2292.

Reference Type BACKGROUND
PMID: 14600188 (View on PubMed)

Tardif JC, Ballantyne CM, Barter P, Dasseux JL, Fayad ZA, Guertin MC, Kastelein JJ, Keyserling C, Klepp H, Koenig W, L'Allier PL, Lesperance J, Luscher TF, Paolini JF, Tawakol A, Waters DD; Can HDL Infusions Significantly QUicken Atherosclerosis REgression (CHI-SQUARE) Investigators. Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial. Eur Heart J. 2014 Dec 7;35(46):3277-86. doi: 10.1093/eurheartj/ehu171. Epub 2014 Apr 29.

Reference Type DERIVED
PMID: 24780501 (View on PubMed)

Other Identifiers

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CER-001-CLIN-002

Identifier Type: -

Identifier Source: org_study_id

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