Effect of CER-001 on Atherosclerosis in Acute Coronary Syndrome (ACS) Patients - Efficacy and Safety: The CHI SQUARE Trial (CHI SQUARE)
Primary Purpose
Acute Coronary Syndrome
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
CER-001
Sponsored by
About this trial
This is an interventional treatment trial for Acute Coronary Syndrome focused on measuring Acute coronary syndrome, HDL mimetic, ApoA-I
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
Sites / Locations
- Heart Center Research LLC
- Mayo Clinic - Arizona
- VA San Diego Health Care Center
- Palm Beach Heart Institute, LLC - Zasa Clinical Research
- Heart and Vascular Institute of Florida
- Jacksonville Center for Clinical Research
- Saint Joseph Research Institute
- The Care Group, LLC
- Suburban Hospital
- University of Michigan Health System
- Detroit Medical Center (DMC) Cardiovascular Institute
- Cardiac and Vascular Research Center of Northern Michigan
- Alegent Research Center
- Buffalo Heart Group
- Buffalo Cardiology & Pulmonary Associates
- University of North Carolina Medical Center
- LeBauer Cardiovascular Research Foundation
- Sanford Heart Center
- South Oklahoma Heart Research
- Penn Presbyterian Medical Center
- Sanford Research / USD
- Baptist Memorial Hospital
- Dallas VA Medical Center
- MultiCare Health System Research Institute / Cardiac Study Center
- Foothills Medical Centre
- Victoria Heart Institute Foundation
- St. John Health Center
- London Health Sciences Center
- St. Michael's Hospital
- Centre de Santé et de Services Sociaux de Laval
- Montreal Heart Institute
- Montreal General Hospital Research Institute
- CSSS du Nord de Lanaudière
- Centre Hospitalier Régional de Trois-Rivières
- Institut Universitaire de Cardiologie et Pneumologie de Québec (IUCPQ)
- Hôpital Cardiologique du Haut-Lévesque
- Clinique Pasteur
- Centre Hospitalier Universitaire de Toulouse Rangueil
- Onze Lieve Vrouwe Gasthius
- Medisch Centrum Leeuwarden
- Medisch Centrum Alkmaar
- Academic Medical Center
- St. Antonius Ziekenhuis Nieuwegein
- Maassstadziekenhuis Cardiology Research
- Catharina Ziekenhuis Eindhoven
- Medisch Spectrum Twente
- Canisius Wilhelmina Ziekenhuis
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Arm Label
Placebo
Low Dose
Mid Dose
High Dose
Arm Description
CER-001 Low Dose
CER-001 Mid Dose
CER-001 High Dose
Outcomes
Primary Outcome Measures
Change in Total Plaque Volume
Absolute change in total plaque volume, as assessed by IVUS, from the baseline measurement to the follow-up taken ~3 weeks following the final dose of study medication (approximately 9 weeks after the baseline assessment)
Secondary Outcome Measures
Percent Change in Plaque Volume
Percent change in total plaque volume, as assessed by IVUS, from the baseline measurement to the follow-up taken ~3 weeks following the final dose of study medication (approximately 9 weeks after the baseline assessment)
Full Information
NCT ID
NCT01201837
First Posted
September 13, 2010
Last Updated
January 29, 2014
Sponsor
Cerenis Therapeutics, SA
1. Study Identification
Unique Protocol Identification Number
NCT01201837
Brief Title
Effect of CER-001 on Atherosclerosis in Acute Coronary Syndrome (ACS) Patients - Efficacy and Safety: The CHI SQUARE Trial
Acronym
CHI SQUARE
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
2. Study Status
Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
March 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cerenis Therapeutics, SA
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Coronary Syndrome
Keywords
Acute coronary syndrome, HDL mimetic, ApoA-I
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
507 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
Low Dose
Arm Type
Experimental
Arm Description
CER-001 Low Dose
Arm Title
Mid Dose
Arm Type
Experimental
Arm Description
CER-001 Mid Dose
Arm Title
High Dose
Arm Type
Experimental
Arm Description
CER-001 High Dose
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Weekly injection
Intervention Type
Drug
Intervention Name(s)
CER-001
Intervention Description
Weekly injection
Primary Outcome Measure Information:
Title
Change in Total Plaque Volume
Description
Absolute change in total plaque volume, as assessed by IVUS, from the baseline measurement to the follow-up taken ~3 weeks following the final dose of study medication (approximately 9 weeks after the baseline assessment)
Time Frame
Baseline and 3 weeks post final dose
Secondary Outcome Measure Information:
Title
Percent Change in Plaque Volume
Description
Percent change in total plaque volume, as assessed by IVUS, from the baseline measurement to the follow-up taken ~3 weeks following the final dose of study medication (approximately 9 weeks after the baseline assessment)
Time Frame
Baseline and 3 weeks post final dose
10. Eligibility
Sex
All
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Claude Tardif, MD
Organizational Affiliation
Montreal Heart Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Heart Center Research LLC
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35801
Country
United States
Facility Name
Mayo Clinic - Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
VA San Diego Health Care Center
City
San Diego
State/Province
California
ZIP/Postal Code
92161
Country
United States
Facility Name
Palm Beach Heart Institute, LLC - Zasa Clinical Research
City
Boynton Beach
State/Province
Florida
ZIP/Postal Code
33472
Country
United States
Facility Name
Heart and Vascular Institute of Florida
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33755
Country
United States
Facility Name
Jacksonville Center for Clinical Research
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
Facility Name
Saint Joseph Research Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
The Care Group, LLC
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Suburban Hospital
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20814
Country
United States
Facility Name
University of Michigan Health System
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Detroit Medical Center (DMC) Cardiovascular Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Cardiac and Vascular Research Center of Northern Michigan
City
Petoskey
State/Province
Michigan
ZIP/Postal Code
49770
Country
United States
Facility Name
Alegent Research Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68124
Country
United States
Facility Name
Buffalo Heart Group
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
Buffalo Cardiology & Pulmonary Associates
City
Williamsville
State/Province
New York
ZIP/Postal Code
14221
Country
United States
Facility Name
University of North Carolina Medical Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
LeBauer Cardiovascular Research Foundation
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27401
Country
United States
Facility Name
Sanford Heart Center
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58122
Country
United States
Facility Name
South Oklahoma Heart Research
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73135
Country
United States
Facility Name
Penn Presbyterian Medical Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Sanford Research / USD
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57104
Country
United States
Facility Name
Baptist Memorial Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38120
Country
United States
Facility Name
Dallas VA Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75016
Country
United States
Facility Name
MultiCare Health System Research Institute / Cardiac Study Center
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Foothills Medical Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 2T9
Country
Canada
Facility Name
Victoria Heart Institute Foundation
City
Victoria
State/Province
British Columbia
ZIP/Postal Code
V8R 4R2
Country
Canada
Facility Name
St. John Health Center
City
St. John's
State/Province
Newfoundland and Labrador
ZIP/Postal Code
A1B 3V6
Country
Canada
Facility Name
London Health Sciences Center
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1W8
Country
Canada
Facility Name
Centre de Santé et de Services Sociaux de Laval
City
Laval
State/Province
Quebec
ZIP/Postal Code
H7M 3L9
Country
Canada
Facility Name
Montreal Heart Institute
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T1C8
Country
Canada
Facility Name
Montreal General Hospital Research Institute
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3G 1A4
Country
Canada
Facility Name
CSSS du Nord de Lanaudière
City
St-Charles-Borromée
State/Province
Quebec
ZIP/Postal Code
J6E 6J2
Country
Canada
Facility Name
Centre Hospitalier Régional de Trois-Rivières
City
Trois-Rivières
State/Province
Quebec
ZIP/Postal Code
G8Z 3R9
Country
Canada
Facility Name
Institut Universitaire de Cardiologie et Pneumologie de Québec (IUCPQ)
City
Quebec
ZIP/Postal Code
G1V 4G5
Country
Canada
Facility Name
Hôpital Cardiologique du Haut-Lévesque
City
Bordeaux
State/Province
PESSAC Cedex
ZIP/Postal Code
33064
Country
France
Facility Name
Clinique Pasteur
City
Toulouse
ZIP/Postal Code
31076
Country
France
Facility Name
Centre Hospitalier Universitaire de Toulouse Rangueil
City
Toulouse
Country
France
Facility Name
Onze Lieve Vrouwe Gasthius
City
Amsterdam
State/Province
AC
ZIP/Postal Code
1091
Country
Netherlands
Facility Name
Medisch Centrum Leeuwarden
City
Leeuwarden
State/Province
AD
ZIP/Postal Code
8934
Country
Netherlands
Facility Name
Medisch Centrum Alkmaar
City
Alkmaar
State/Province
Amsterdam
ZIP/Postal Code
JD 1815
Country
Netherlands
Facility Name
Academic Medical Center
City
Amsterdam
State/Province
AZ
ZIP/Postal Code
1105
Country
Netherlands
Facility Name
St. Antonius Ziekenhuis Nieuwegein
City
Nieuwegein
State/Province
CM
ZIP/Postal Code
3430
Country
Netherlands
Facility Name
Maassstadziekenhuis Cardiology Research
City
Rotterdam
State/Province
DZ
ZIP/Postal Code
3079
Country
Netherlands
Facility Name
Catharina Ziekenhuis Eindhoven
City
Eindhoven
State/Province
EJ
ZIP/Postal Code
5623
Country
Netherlands
Facility Name
Medisch Spectrum Twente
City
Enschede
State/Province
ER
ZIP/Postal Code
7513
Country
Netherlands
Facility Name
Canisius Wilhelmina Ziekenhuis
City
Nijmegen
State/Province
SZ
ZIP/Postal Code
6532
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
10195926
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.
Results Reference
background
PubMed Identifier
10441095
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.
Results Reference
background
PubMed Identifier
11914243
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.
Results Reference
background
PubMed Identifier
18389214
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.
Results Reference
background
PubMed Identifier
19349317
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.
Results Reference
background
PubMed Identifier
18832751
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.
Results Reference
background
PubMed Identifier
20538165
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.
Results Reference
background
PubMed Identifier
17387133
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.
Results Reference
background
PubMed Identifier
14600188
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.
Results Reference
background
PubMed Identifier
24780501
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.
Results Reference
derived
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Effect of CER-001 on Atherosclerosis in Acute Coronary Syndrome (ACS) Patients - Efficacy and Safety: The CHI SQUARE Trial
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