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

Acute Coronary Syndrome Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01201837
• Other study ID #: CER-001-CLIN-002
• Status: Completed
• Phase: Phase 2
• First received: September 13, 2010
• Last updated: January 29, 2014
• Start date: March 2011
• Est. completion date: March 2013

Study information

• Verified date: January 2014
• Source: Cerenis Therapeutics, SA
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 507
• Est. completion date: March 2013
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Atherosclerosis
• Syndrome

Intervention

Drug:
• Placebo
Weekly injection
• CER-001
Weekly injection

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Cerenis Therapeutics, SA

Countries where clinical trial is conducted

United States,  Canada,  France,  Netherlands, 

References & Publications (9)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Spieker LE, Sudano I, Hürlimann D, Lerch PG, Lang MG, Binggeli C, Corti R, Ruschitzka F, Lüscher TF, Noll G. High-density lipoprotein restores endothelial function in hypercholesterolemic men. Circulation. 2002 Mar 26;105(12):1399-402. — View Citation

Tardif JC, Grégoire J, L'Allier PL, Ibrahim R, Lespérance J, Heinonen TM, Kouz S, Berry C, Basser R, Lavoie MA, Guertin MC, Rodés-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. Epub 2007 Mar 26. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Baseline and 3 weeks post final dose	No
Secondary	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)	Baseline and 3 weeks post final dose	No