Clinical trial NCT01201837: Effect of CER-001 on Atherosclerosis in Acute Coronary Syndrome (ACS) Patients - Efficacy and Safety: The CHI SQUARE Trial
Official title: CHI SQUARE: Can HDL Infusions Significantly Quicken Atherosclerosis Regression? A Phase II, Multi-Center, Double-Blind, Ascending Dose, Placebo-Controlled, Dose-Finding Trial of CER-001 or Placebo in Subjects With Acute Coronary Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Coronary Syndrome
Keywords: Acute coronary syndrome
HDL mimetic
ApoA-I
Lead sponsor: Cerenis Therapeutics, SA
Sponsor class: INDUSTRY
First posted: 2010-09-15
Enrollment: 507
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Change in Total Plaque Volume
timeFrame: Baseline and 3 weeks post final dose
Secondary outcomes:
measure: Percent Change in Plaque Volume
timeFrame: Baseline and 3 weeks post final dose
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Heart Center Research LLC
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic - Arizona
state: Arizona
city: San Diego
country: United States
facility: VA San Diego Health Care Center
state: California
city: Boynton Beach
country: United States
facility: Palm Beach Heart Institute, LLC - Zasa Clinical Research
state: Florida
city: Clearwater
country: United States
facility: Heart and Vascular Institute of Florida
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Atlanta
country: United States
facility: Saint Joseph Research Institute
state: Georgia
city: Indianapolis
country: United States
facility: The Care Group, LLC
state: Indiana
city: Bethesda
country: United States
facility: Suburban Hospital
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Detroit
country: United States
facility: Detroit Medical Center (DMC) Cardiovascular Institute
state: Michigan
city: Petoskey
country: United States
facility: Cardiac and Vascular Research Center of Northern Michigan
state: Michigan
city: Omaha
country: United States
facility: Alegent Research Center
state: Nebraska
city: Buffalo
country: United States
facility: Buffalo Heart Group
state: New York
city: Williamsville
country: United States
facility: Buffalo Cardiology & Pulmonary Associates
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Medical Center
state: North Carolina
city: Greensboro
country: United States
facility: LeBauer Cardiovascular Research Foundation
state: North Carolina
city: Fargo
country: United States
facility: Sanford Heart Center
state: North Dakota
city: Oklahoma City
country: United States
facility: South Oklahoma Heart Research
state: Oklahoma
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Research / USD
state: South Dakota
city: Memphis
country: United States
facility: Baptist Memorial Hospital
state: Tennessee
city: Dallas
country: United States
facility: Dallas VA Medical Center
state: Texas
city: Tacoma
country: United States
facility: MultiCare Health System Research Institute / Cardiac Study Center
state: Washington
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Victoria
country: Canada
facility: Victoria Heart Institute Foundation
state: British Columbia
city: St. John's
country: Canada
facility: St. John Health Center
state: Newfoundland and Labrador
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Laval
country: Canada
facility: Centre de Santé et de Services Sociaux de Laval
state: Quebec
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montreal
country: Canada
facility: Montreal General Hospital Research Institute
state: Quebec
city: St-Charles-Borromée
country: Canada
facility: CSSS du Nord de Lanaudière
state: Quebec
city: Trois-Rivières
country: Canada
facility: Centre Hospitalier Régional de Trois-Rivières
state: Quebec
city: Quebec
country: Canada
facility: Institut Universitaire de Cardiologie et Pneumologie de Québec (IUCPQ)
city: Bordeaux
country: France
facility: Hôpital Cardiologique du Haut-Lévesque
state: PESSAC Cedex
city: Toulouse
country: France
facility: Clinique Pasteur
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire de Toulouse Rangueil
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthius
state: AC
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
state: AD
city: Alkmaar
country: Netherlands
facility: Medisch Centrum Alkmaar
state: Amsterdam
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
state: AZ
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis Nieuwegein
state: CM
city: Rotterdam
country: Netherlands
facility: Maassstadziekenhuis Cardiology Research
state: DZ
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis Eindhoven
state: EJ
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
state: ER
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Ziekenhuis
state: SZ
Study officials:
affiliation: Montreal Heart Institute
name: Jean-Claude Tardif, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.