Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia - Full Text View

Sponsor:	Genzyme
Collaborator:	Isis Pharmaceuticals
Information provided by:	Genzyme
ClinicalTrials.gov Identifier:	NCT00607373

Purpose

The purpose of this study is to evaluate the safety and efficacy of ISIS 301012 (mipomersen) in subjects with homozygous familial hypercholesterolemia on lipid-lowering therapy.

Condition	Intervention	Phase
Lipid Metabolism, Inborn Errors Hypercholesterolemia, Autosomal Dominant Hyperlipidemias Metabolic Diseases Hyperlipoproteinemia Type II Metabolism, Inborn Errors Genetic Diseases, Inborn Infant, Newborn, Diseases Metabolic Disorder Congenital Abnormalities Hypercholesterolemia Hyperlipoproteinemias Dyslipidemias Lipid Metabolism Disorders	Drug: ISIS 301012 (mipomersen sodium) Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of ISIS 301012 as Add-on Therapy in Homozygous Familial Hypercholesterolemia Subjects

Resource links provided by NLM:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease Farber lipogranulomatosis hypercholesterolemia Help Me Understand Genetics

MedlinePlus related topics: Cholesterol Common Infant and Newborn Problems Metabolic Disorders Uncommon Infant and Newborn Problems

Drug Information available for: Mipomersen sodium

U.S. FDA Resources

Further study details as provided by Genzyme:

Primary Outcome Measures:

To evaluate the LDL-C lowering efficacy of ISIS 301012 (mipomersen) in subjects with homozygous familial hypercholesterolemia on lipid-lowering therapy [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To evaluate the incremental apoB-lowering efficacy of ISIS 301012 (mipomersen) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
To assess the incremental total cholesterol-lowering efficacy of ISIS 301012 (mipomersen) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
To assess the incremental non-HDL-C-lowering efficacy of ISIS 301012 (mipomersen) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
To evaluate the incremental effects of ISIS 301012 (mipomersen) on triglycerides, VLDL-C, HDL-C, apoA-1, Lp(a), lipoprotein subclasses, and hsCRP [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment:	51
Study Start Date:	September 2007
Study Completion Date:	April 2009
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: ISIS 301012 (mipomersen)	Drug: ISIS 301012 (mipomersen sodium) 200 mg ISIS 301012 (mipomersen) administered once a week for 26 weeks as a 1 mL subcutaneous injection. Subjects weighing less than 50 kg will receive a lower dose of 160 mg (0.8mL) ISIS 301012 (mipomersen) Other Name: ISIS 301012
Placebo Comparator: Placebo	Drug: Placebo 1 mL subcutaneous injection once a week for 26 weeks. Subjects weighing less than 50 kg will receive 0.8 mL subcutaneous injection.

Detailed Description:

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder of lipoprotein metabolism characterized by markedly elevated low density lipoprotein (LDL), premature onset of atherosclerosis and development of xanthomata. Patients with homozygous familial hypercholesterolemia (HoFH) have a severe disease that presents in childhood with total cholesterol typically in the 650 to 1000 mg/dL range.

ISIS 301012(mipomersen)is an antisense drug that reduces a protein in the liver cells called apolipoprotein B-100 (apoB-100). ApoB-100 plays a role in producing low density lipoprotein cholesterol (LDL-C)(the "bad" cholesterol) and moving it from the liver to one's bloodstream. High LDL-C is an independent risk factor for the development of coronary heart disease (CHD) or other diseases of blood vessels. It has been shown that lowering LDL-C reduces the risk of heart attacks and other major adverse cardiovascular events.

The purpose of this study is to determine whether mipomersen safely and effectively lowers LDL-C in subjects with HoFH who are already on a stable dose of other lipid-lowering agents.

Eligibility

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

Criteria

Inclusion Criteria:

Diagnosis of Homozygous Familial Hypercholesterolemia (HoFH)
Stable lipid-lowering therapy for 12 weeks
Stable weight for 6 weeks
Stable low fat diet for 8 weeks

Exclusion Criteria:

Significant health problems in the recent past including heart attack, stroke, blood disorders, cancer, or digestive problems

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00607373

Locations

United States, North Carolina

Charlotte, North Carolina, United States, 28204
United States, Ohio

Cincinnati, Ohio, United States, 45212
Brazil

Sao Paulo, SP, Brazil, 05403-000
Canada, Quebec

Chicoutimi, Quebec, Canada, G7H 5H6

Ste Foy, Quebec, Canada, G1V 4G2
Singapore

Mistri Wing, Singapore, 168752
South Africa

Observatory, South Africa, 7925

Parktown, South Africa, 2193
Taiwan

Taipei, Taiwan, 11217
United Kingdom

London, United Kingdom, WC1N 3BG

Sponsors and Collaborators

Genzyme

Isis Pharmaceuticals

Investigators

Study Director:

Medical Monitor

Genzyme

More Information

No publications provided by Genzyme

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Raal FJ, Santos RD, Blom DJ, Marais AD, Charng MJ, Cromwell WC, Lachmann RH, Gaudet D, Tan JL, Chasan-Taber S, Tribble DL, Flaim JD, Crooke ST. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet. 2010 Mar 20;375(9719):998-1006.

Responsible Party:	Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier:	NCT00607373 History of Changes
Other Study ID Numbers:	301012-CS5, 2005-003449-15
Study First Received:	January 22, 2008
Last Updated:	October 2, 2010
Health Authority:	United States: Food and Drug Administration; Canada: Health Canada; United Kingdom: Medicines and Healthcare Products Regulatory Agency; South Africa: Medicines Control Council; Singapore: Health Sciences Authority; Taiwan: Department of Health; Brazil: National Health Surveillance Agency

Keywords provided by Genzyme:

Apolipoprotein B
Homozygous Familial Hypercholesterolemia
LDL-receptor gene

Additional relevant MeSH terms:

Congenital Abnormalities
Genetic Diseases, Inborn
Hypercholesterolemia
Hyperlipoproteinemia Type II
Hyperlipidemias
Hyperlipoproteinemias

Infant, Newborn, Diseases
Lipid Metabolism, Inborn Errors
Metabolic Diseases
Metabolism, Inborn Errors
Lipid Metabolism Disorders
Dyslipidemias

ClinicalTrials.gov processed this record on February 09, 2012