NCT01412034

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
23

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Nov 2011

Geographic Reach
5 countries

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 5, 2011

Completed
3 days until next milestone

First Posted

Study publicly available on registry

August 8, 2011

Completed
3 months until next milestone

Study Start

First participant enrolled

November 1, 2011

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2013

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2014

Completed
Last Updated

August 18, 2015

Status Verified

July 1, 2015

Enrollment Period

1.9 years

First QC Date

August 5, 2011

Last Update Submit

July 28, 2015

Conditions

Homozygous Familial Hypercholesterolemia

Keywords

Homozygous Familial HypercholesterolemiaFamilial HypercholesterolemiaHDL mimeticApoA-1

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (1)

  • Change in carotid vessel wall volume

    Baseline then 6 months and/or ~2 weeks post final dose

Study Arms (1)

CER-001

EXPERIMENTAL

Open label single arm study of CER-001

Drug: CER-001

Interventions

CER-001DRUG

Biweekly infusion

CER-001

Eligibility Criteria

Age12 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Clinical Research Facility

Hartford, Connecticut, 06102, United States

Location

Clinical Research Facility

North Massapequa, New York, 11758, United States

Location

Clinical Research Facility

Chicoutimi, Quebec, G7H 7P2, Canada

Location

Clinical Research Facility

Québec, Quebec, G1V4M6, Canada

Location

Clinical Research Facility

Rome, 100161, Italy

Location

Clinical Research Facility

Amsterdam, 1105AZ, Netherlands

Location

Clinical Research Facility

Maastricht, 6229 HX, Netherlands

Location

Clinical Research Facility

Nijmegen, 6500 HB, Netherlands

Location

Clinical Research Facility

Manchester, M13 9WL, United Kingdom

Location

Related 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. doi: 10.1161/01.cir.100.6.594.

    PMID: 10441095BACKGROUND

  • 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.

    PMID: 10195926BACKGROUND

  • 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: 18389214BACKGROUND

  • 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: 18832751BACKGROUND

  • 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: 14600188BACKGROUND

  • 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: 17387133BACKGROUND

  • 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: 20538165BACKGROUND

  • 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: 11914243RESULT

MeSH Terms

Conditions

Homozygous Familial HypercholesterolemiaHyperlipoproteinemia Type II

Interventions

CER-001

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesHyperlipoproteinemiasHyperlipidemiasDyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • John J. Kastelein, MD PhD

    Amsterdam UMC, location VUmc

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 5, 2011

First Posted

August 8, 2011

Study Start

November 1, 2011

Primary Completion

October 1, 2013

Study Completion

August 1, 2014

Last Updated

August 18, 2015

Record last verified: 2015-07

Locations

US(2)NL(3)GB(1)CA(2)IT(1)