Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia - Full Text View

Sponsor:	Genzyme
Collaborator:	Isis Pharmaceuticals
Information provided by (Responsible Party):	Genzyme
ClinicalTrials.gov Identifier:	NCT00477594

Purpose

The purpose of this study is to evaluate the safety and efficacy of mipomersen in subjects with familial hypercholesterolemia on lipid-lowering therapy who have completed either the 301012-CS8 (NCT00280995) or 301012-CS9 (NCT00281008) clinical drug trials.

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: mipomersen sodium	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open-Label Extension Study to Assess the Long-Term Safety and Efficacy of ISIS 301012 in Subjects With Familial Hypercholesterolemia

Resource links provided by NLM:

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

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

U.S. FDA Resources

Further study details as provided by Genzyme:

Primary Outcome Measures:

Percent reduction of low density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo-B), total cholesterol, and non-high density lipoprotein cholesterol (non-HDL-C) level from baseline [ Time Frame: 6, 12, 18, 24, 30 & 36 months of exposure ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Summary of Adverse Events [ Time Frame: 3 years of treatment and 24 weeks of follow-up ] [ Designated as safety issue: Yes ]
Platelets, liver transaminases, renal function tests [ Time Frame: 3 years of treatment and 24 weeks of follow-up ] [ Designated as safety issue: Yes ]
Laboratory Results: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Serum Creatinine, Platelet counts, Urine Protein, Prothrombin time (PT) [ Time Frame: 3 years of treatment and 24 weeks of follow-up ] [ Designated as safety issue: Yes ]
Vital signs (including respiration rate, pulse, temperature, and systolic and diastolic BP) and electrocardiogram (ECG) [ Time Frame: 3 years of treatment and 24 weeks of follow-up ] [ Designated as safety issue: Yes ]

Enrollment:	22
Study Start Date:	May 2007
Study Completion Date:	July 2011
Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: mipomersen 200 mg per week	Drug: mipomersen sodium 200 mg subcutaneous once a week. Other Name: ISIS 301012
Experimental: mipomersen 200 mg every other week	Drug: mipomersen sodium 200 mg subcutaneous once every other week Other Name: ISIS 301012

Detailed Description:

Familial Hypercholesterolemia (FH) is an autosomal dominant metabolic disorder characterized by markedly elevated low density lipoprotein (LDL), premature onset of atherosclerosis and development of xanthomata. There are two distinct subpopulations that have a high unmet medical need due to the lack of alternative therapy. These are the homozygotes who have two defective LDL receptor (LDL-R) genes, and heterozygotes with a history of cardiovascular disease (CVD) on maximally tolerated therapy. Treatment for FH is directed at lowering plasma levels of LDL-C.

Mipomersen is an antisense drug targeted to human apoB-100, the principal apolipoprotein of atherogenic LDL-C and its metabolic precursor, VLDL. Mipomersen is complimentary to the coding region of the mRNA for apoB-100. Inhibition of apoB-100 would be expected to impair very low density lipoprotein (VLDL) synthesis and result in lowered levels of LDL-C.

In early clinical trials, mipomersen has been shown to reduce levels of LDL-C to recommended target levels in some subjects.

The intent of this trial is to gather additional information to evaluate the overall benefit-risk relationship of the drug, and to provide ongoing therapy for FH subjects who participated in two prior mipomersen trials (301012-CS8 (NCT00280995) and 301012-CS9(NCT00281008)).

Eligibility

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

Criteria

Inclusion Criteria:

- Satisfactory completion of dosing and Week 7 or Week 15 assessments (depending on the treatment and dose received) in their initial study (Protocol 301012-CS8 (NCT00280995) or 301012-CS9 (NCT00281008)).

Exclusion Criteria:

- Have a new condition or worsening of existing condition which in the opinion of the Investigator would make the subject unsuitable for enrollment, or could interfere with subject's participation in or completion of the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00477594

Locations

United States, Illinois

Chicago, Illinois, United States, 60654
United States, Maine

Auburn, Maine, United States, 04210

Biddeford, Maine, United States, 04005

Scarborough, Maine, United States, 04074
United States, Ohio

Cincinnati, Ohio, United States, 45212

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):

Patel N, Hegele RA. Mipomersen as a potential adjunctive therapy for hypercholesterolemia. Expert Opin Pharmacother. 2010 Oct;11(15):2569-72. Review.

Responsible Party:	Genzyme
ClinicalTrials.gov Identifier:	NCT00477594 History of Changes
Other Study ID Numbers:	301012-CS17
Study First Received:	May 22, 2007
Last Updated:	January 18, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Genzyme:

Familial Hypercholesterolemia
Heterozygous Familial Hypercholesterolemia
Homozygous Familial Hypercholesterolemia

ISIS 301012
mipomersen
Open Label Extension

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 May 22, 2012