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

Homozygous Familial Hypercholesterolemia Clinical Trial

— MODE  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01412034
• Other study ID #: CER-001-CLIN-003
• Status: Completed
• Phase: Phase 2
• First received: August 5, 2011
• Last updated: July 28, 2015
• Start date: November 2011
• Est. completion date: August 2014

Study information

• Verified date: July 2015
• Source: Cerenis Therapeutics, SA
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Italy: The Italian Medicines AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: August 2014
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Homozygous Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Drug:
• CER-001
Biweekly infusion

Locations

Country	Name	City	State
Canada	Clinical Research Facility	Chicoutimi	Quebec
Canada	Clinical Research Facility	Quebec
Italy	Clinical Research Facility	Rome
Netherlands	Clinical Research Facility	Amsterdam
Netherlands	Clinical Research Facility	Maastricht
Netherlands	Clinical Research Facility	Nijmegen
United Kingdom	Clinical Research Facility	Manchester
United States	Clinical Research Facility	Hartford	Connecticut
United States	Clinical Research Facility	N. Massapequa	New York

Sponsors (1)

Lead Sponsor	Collaborator
Cerenis Therapeutics, SA

Countries where clinical trial is conducted

United States,  Canada,  Italy,  Netherlands,  United Kingdom, 

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	Percent change from baseline to follow-up in carotid mean vessel wall area	Percent change from baseline to follow-up in carotid mean vessel wall area	Baseline then 6 months and/or ~2 weeks post final dose	No
Secondary	Change in carotid vessel wall volume	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.	Baseline then 6 months and/or ~2 weeks post final dose	No