Effect of CER-001 on Plaque Volume in Homozygous Familial Hypercholesterolemia (HoFH) Subjects - Full Text View

Purpose

The available medications used to treat HoFH are targeted at reducing circulating levels of total and LDL-cholesterol. These measures can retard the progression of cardiovascular disease, however, they are unlikely to regress existing disease due to years of cholesterol accumulation in the vessel walls and therefore cannot adequately reduce the existing risk for an ischemic event. HDL has multiple actions that could lead to plaque stabilization and regression, 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, a recombinant human Apo-A-1 based HDL mimetic, on indices of atherosclerotic plaque progression and regression as assessed by 3Tesla MRI measurements in patients with HoFH.

Condition	Intervention	Phase
Homozygous Familial Hypercholesterolemia	Drug: CER-001	Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Modifying Orphan Disease Evaluation (MODE) Study: A Multicenter, Open-label Study of the Effects of CER-001 on Plaque Volume in Subjects With Homozygous Familial Hypercholesterolemia (HoFH)

Resource links provided by NLM:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease hypercholesterolemia

MedlinePlus related topics: Cholesterol

Genetic and Rare Diseases Information Center resources: Hyperlipoproteinemia Type 2 Sphingolipidosis

U.S. FDA Resources

Further study details as provided by Cerenis Therapeutics, SA:

Primary Outcome Measures:

Percent change from baseline to follow-up in carotid mean vessel wall area [ Time Frame: Baseline then 6 months and/or ~2 weeks post final dose ] [ Designated as safety issue: No ]
Percent change from baseline to follow-up in carotid mean vessel wall area

Secondary Outcome Measures:

Change in carotid vessel wall volume [ Time Frame: Baseline then 6 months and/or ~2 weeks post final dose ] [ Designated as safety issue: No ]
Percent change in carotid vessel wall volume , as assessed by 3TMRI, from the baseline measurement to the follow up taken ~2 weeks following the final dose of study medication.


Enrollment:	23
Study Start Date:	November 2011
Study Completion Date:	August 2014
Primary Completion Date:	October 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: CER-001 Open label single arm study of CER-001	Drug: CER-001 Biweekly infusion

Eligibility


Ages Eligible for Study:	12 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female subject 12 years or older
Subject presents with Homozygous FH

Exclusion Criteria:

Weight >100 kg
Subjects with significant health problems in the recent past including blood disorders, cancer, or digestive problems
Female subjects of child-bearing potential
Known major hematologic, renal , hepatic, metabolic, gastrointestinal or endocrine dysfunction
Contraindication to MRI scanning that would preclude the use of contrast-enhanced 3TMRI

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01412034

Locations


United States, Connecticut
Clinical Research Facility
Hartford, Connecticut, United States, 06102
United States, New York
Clinical Research Facility
N. Massapequa, New York, United States, 11758
Canada, Quebec
Clinical Research Facility
Chicoutimi, Quebec, Canada, G7H 7P2
Canada
Clinical Research Facility
Quebec, Canada, G1V4M6
Italy
Clinical Research Facility
Rome, Italy, 100161
Netherlands
Clinical Research Facility
Amsterdam, Netherlands, 1105AZ
Clinical Research Facility
Maastricht, Netherlands, 6229 HX
Clinical Research Facility
Nijmegen, Netherlands, 6500 HB
United Kingdom
Clinical Research Facility
Manchester, United Kingdom, M13 9WL

Sponsors and Collaborators

Cerenis Therapeutics, SA

Investigators


Principal Investigator:	John J. Kastelein, MD PhD	Amsterdam Medical Center

More Information

Publications:

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.

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.

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.

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.

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.

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.

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.

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.


Responsible Party:	Cerenis Therapeutics, SA
ClinicalTrials.gov Identifier:	NCT01412034 History of Changes
Other Study ID Numbers:	CER-001-CLIN-003
Study First Received:	August 5, 2011
Last Updated:	February 4, 2015
Health Authority:	United States: Food and Drug Administration Canada: Health Canada France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Italy: The Italian Medicines Agency Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Cerenis Therapeutics, SA:


Homozygous Familial Hypercholesterolemia Familial Hypercholesterolemia HDL mimetic ApoA-1

Additional relevant MeSH terms:


Hypercholesterolemia Hyperlipoproteinemia Type II Dyslipidemias Genetic Diseases, Inborn Hyperlipidemias	Hyperlipoproteinemias Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Metabolic Diseases Metabolism, Inborn Errors

ClinicalTrials.gov processed this record on February 25, 2015

Effect of CER-001 on Plaque Volume in Homozygous Familial Hypercholesterolemia (HoFH) Subjects (MODE)