Clinical trial NCT01412034: Effect of CER-001 on Plaque Volume in Homozygous Familial Hypercholesterolemia (HoFH) Subjects
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Homozygous Familial Hypercholesterolemia
Keywords: Homozygous Familial Hypercholesterolemia
Familial Hypercholesterolemia
HDL mimetic
ApoA-1
Lead sponsor: Cerenis Therapeutics, SA
Sponsor class: INDUSTRY
First posted: 2011-08-08
Enrollment: 23
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Percent change from baseline to follow-up in carotid mean vessel wall area
timeFrame: Baseline then 6 months and/or ~2 weeks post final dose
Secondary outcomes:
measure: Change in carotid vessel wall volume
timeFrame: Baseline then 6 months and/or ~2 weeks post final dose
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Clinical Research Facility
state: Connecticut
city: N. Massapequa
country: United States
facility: Clinical Research Facility
state: New York
city: Chicoutimi
country: Canada
facility: Clinical Research Facility
state: Quebec
city: Quebec
country: Canada
facility: Clinical Research Facility
city: Rome
country: Italy
facility: Clinical Research Facility
city: Amsterdam
country: Netherlands
facility: Clinical Research Facility
city: Maastricht
country: Netherlands
facility: Clinical Research Facility
city: Nijmegen
country: Netherlands
facility: Clinical Research Facility
city: Manchester
country: United Kingdom
facility: Clinical Research Facility
Study officials:
affiliation: Amsterdam UMC, location VUmc
name: John J. Kastelein, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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.