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

NCT01201837 | Completed Phase 2 DMC

• 1 other identifier: CER-001-CLIN-002
• Study Type: interventional
• Target: 507
• Locations: 4 countries
• Sites: 47

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).

Conditions

Acute Coronary Syndrome

Keywords

Acute coronary syndrome; HDL mimetic; ApoA-I

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Percent Change in Plaque Volume

  Baseline and 3 weeks post final dose

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Low Dose

EXPERIMENTAL

CER-001 Low Dose

Drug: CER-001

Mid Dose

EXPERIMENTAL

CER-001 Mid Dose

Drug: CER-001

High Dose

EXPERIMENTAL

CER-001 High Dose

Drug: CER-001

Interventions

Placebo DRUG

Weekly injection

Placebo

CER-001 DRUG

Weekly injection

High Dose; Low Dose; Mid Dose

Eligibility Criteria

• Age: Up to 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cerenis Therapeutics, SA: lead

Study Sites (47)

Heart Center Research LLC

Huntsville, Alabama, 35801, United States

Location

Mayo Clinic - Arizona

Phoenix, Arizona, 85054, United States

Location

VA San Diego Health Care Center

San Diego, California, 92161, United States

Location

Palm Beach Heart Institute, LLC - Zasa Clinical Research

Boynton Beach, Florida, 33472, United States

Location

Heart and Vascular Institute of Florida

Clearwater, Florida, 33755, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Saint Joseph Research Institute

Atlanta, Georgia, 30342, United States

Location

The Care Group, LLC

Indianapolis, Indiana, 46260, United States

Location

Suburban Hospital

Bethesda, Maryland, 20814, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Detroit Medical Center (DMC) Cardiovascular Institute

Detroit, Michigan, 48201, United States

Location

Cardiac and Vascular Research Center of Northern Michigan

Petoskey, Michigan, 49770, United States

Location

Alegent Research Center

Omaha, Nebraska, 68124, United States

Location

Buffalo Heart Group

Buffalo, New York, 14215, United States

Location

Buffalo Cardiology & Pulmonary Associates

Williamsville, New York, 14221, United States

Location

University of North Carolina Medical Center

Chapel Hill, North Carolina, 27599, United States

Location

LeBauer Cardiovascular Research Foundation

Greensboro, North Carolina, 27401, United States

Location

Sanford Heart Center

Fargo, North Dakota, 58122, United States

Location

South Oklahoma Heart Research

Oklahoma City, Oklahoma, 73135, United States

Location

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Sanford Research / USD

Sioux Falls, South Dakota, 57104, United States

Location

Baptist Memorial Hospital

Memphis, Tennessee, 38120, United States

Location

Dallas VA Medical Center

Dallas, Texas, 75016, United States

Location

MultiCare Health System Research Institute / Cardiac Study Center

Tacoma, Washington, 98405, United States

Location

Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

Victoria Heart Institute Foundation

Victoria, British Columbia, V8R 4R2, Canada

Location

St. John Health Center

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

Location

London Health Sciences Center

London, Ontario, N6A 5A5, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Centre de Santé et de Services Sociaux de Laval

Laval, Quebec, H7M 3L9, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T1C8, Canada

Location

Montreal General Hospital Research Institute

Montreal, Quebec, H3G 1A4, Canada

Location

Institut Universitaire de Cardiologie et Pneumologie de Québec (IUCPQ)

Québec, Quebec, G1V 4G5, Canada

Location

CSSS du Nord de Lanaudière

Saint-Charles-Borromée, Quebec, J6E 6J2, Canada

Location

Centre Hospitalier Régional de Trois-Rivières

Trois-Rivières, Quebec, G8Z 3R9, Canada

Location

Hôpital Cardiologique du Haut-Lévesque

Bordeaux, Pessac Cedex, 33064, France

Location

Clinique Pasteur

Toulouse, 31076, France

Location

Centre Hospitalier Universitaire de Toulouse Rangueil

Toulouse, France

Location

Onze Lieve Vrouwe Gasthius

Amsterdam, AC, 1091, Netherlands

Location

Medisch Centrum Leeuwarden

Leeuwarden, AD, 8934, Netherlands

Location

Medisch Centrum Alkmaar

Alkmaar, Amsterdam, JD 1815, Netherlands

Location

Academic Medical Center

Amsterdam, AZ, 1105, Netherlands

Location

St. Antonius Ziekenhuis Nieuwegein

Nieuwegein, CM, 3430, Netherlands

Location

Maassstadziekenhuis Cardiology Research

Rotterdam, DZ, 3079, Netherlands

Location

Catharina Ziekenhuis Eindhoven

Eindhoven, EJ, 5623, Netherlands

Location

Medisch Spectrum Twente

Enschede, ER, 7513, Netherlands

Location

Canisius Wilhelmina Ziekenhuis

Nijmegen, SZ, 6532, Netherlands

Location

Related Publications (10)

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  PMID: 10195926 BACKGROUND

• 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.

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• 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.

  PMID: 11914243 BACKGROUND

• 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.

  PMID: 18389214 BACKGROUND

• 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.

  PMID: 19349317 BACKGROUND

• 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.

  PMID: 18832751 BACKGROUND

• 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.

  PMID: 20538165 BACKGROUND

• 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.

  PMID: 17387133 BACKGROUND

• 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.

  PMID: 14600188 BACKGROUND

• 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.

  PMID: 24780501 DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

CER-001

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Study Officials

• Jean-Claude Tardif, MD

  Montreal Heart Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 13, 2010
• First Posted: September 15, 2010
• Study Start: March 1, 2011
• Primary Completion: October 1, 2012
• Study Completion: March 1, 2013
• Last Updated: March 3, 2014

Record last verified: 2014-01

Locations

CA (11); US (24); FR (3); NL (9)