Exploratory Study of Plaque Regression

Heterozygous Familial Hypercholesterolemia Clinical Trial

— EXPRESS  

Official title:

EXPLORATORY STUDY OF PLAQUE REGRESSION:A Phase II Single Center Open-Label Exploratory Trial of the Effect of CER 001 in Subjects With Familial Hypercholesterolemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01515241
• Other study ID #: CER-001-CLIN-005
• Status: Completed
• Phase: Phase 2
• First received: January 18, 2012
• Last updated: January 29, 2014
• Start date: January 2012
• Est. completion date: May 2012

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

Despite the availability of several classes of very effective drugs available to treat heterozygous Familial Hypercholesterolemia (HeFH), there remains a large unmet medical need for new, effective and well tolerated therapies. There are a number of therapies given on a chronic basis to reduce long term risk, such as statins, fibrates, niacin, omega 3 fatty acids, resins, cholesterol absorption inhibitors and antiplatelet or anticoagulant drugs, but subjects with heterozygous Familial Hypercholesterolemia remain at high risk for cardiovascular events. There is still a need for acute therapies that can lead to rapid pacification of unstable plaque in order to reduce the risk of these events. This study will assess the effects of CER-001 , a recombinant human Apo-A-1 based HDL mimetic, on indices of atherosclerotic plaque progression and regression as assessed by 3Tesla MRI (3TMRI)and intravascular ultrasound (IVUS) evaluations in patients with HeFH.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: May 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or Female subjects at least 18 years old

• Subject presents heterozygous FH, known CHD and receiving maximally tolerated lipid modifying therapy, at stable doses for at least 3 months

• LDL-C of > 110 mg/dl

• Angiographic evidence of coronary artery disease with suitable "target" coronary artery for IVUS

Exclusion Criteria:

• Confirmed diagnosis of homozygous FH

• Significant health problems (other than cardiovascular disease) in the recent past including blood disorders, cancer, or digestive problems

• Female subjects not meeting the study definition of non child-bearing potential

• Use of an investigational agent within 30 days of the first CER-001 dose

• Receiving current lipid apheresis

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heterozygous Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Drug:
• CER-001
Weekly injection

Locations

Country	Name	City	State
Canada	Montreal Heart Institute	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Cerenis Therapeutics, SA

Country where clinical trial is conducted

Canada, 

References & Publications (8)

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	Nominal change in total plaque volume (ACTPV), as assessed by 3D IVUS, from the baseline measurement to the follow-up taken ~3 weeks following the final dose of study medication (approximately 10 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 (PCTPV), as assessed by IVUS, from the baseline measurement to the follow up taken approximately 3 weeks following the final dose of study medication (approximately 10 weeks after the baseline assessment)	Baseline and 3 weeks post final dose	No
Secondary	Change in carotid plaque volume	Percent change in total carotid plaque volume, as assessed by 3TMRI, from the baseline measurement to the follow up taken approximately 3 weeks following the final dose of study medication	Baseline and 3 weeks post final dose	No