Efficacy and Safety Study of ISIS 301012 (Mipomersen) as Add-on in Familial Hypercholesterolemic Patients With Coronary Artery Disease

NCT ID: NCT00706849

Last Updated: 2016-09-09

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

124 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-07-31

Study Completion Date

2010-05-31

Brief Summary

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The purpose of this study is to determine whether mipomersen safely and effectively lowers low-density lipoprotein cholesterol (LDL-C) in patients with Heterozygous Familial Hypercholesterolemia (HeFH) and coronary artery disease (CAD) who are already on a stable dose of other lipid-lowering agents (including maximally tolerated statin therapy).

Detailed Description

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Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder of lipoprotein metabolism characterized by markedly elevated LDL-C, premature onset of atherosclerosis and development of xanthomata. Patients with heterozygous familial hypercholesterolemia typically have total plasma cholesterol between 350 to 550 mg/dL and disease onset in their third and fourth decade.

Mipomersen (ISIS 301012) is an antisense drug that reduces a protein in the liver cells called apolipoprotein B (apo-B). Apo-B plays a role in producing low density lipoprotein cholesterol (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.

This study consisted of a 26-week treatment period and a 24-week post-treatment follow-up period (with the exception of patients who enrolled in the open-label extension study \[Study 301012-CS6; NCT00694109\]). The treatment period spanned the time during which the study treatment was administered until the later of the primary efficacy time point (PET) or 14 days beyond the last day of study drug administration. The post-treatment follow-up period began the day after completion of the treatment period and ended on the day of the patient's last contact date within the study.

Following treatment and Week 28 evaluations, eligible patients who tolerated study drug could elect to enroll in an open-label extension study (301012-CS6). Patients who were not eligible for or who elected not to enroll in the open-label extension study and patients who discontinued during the 26-week treatment period were followed in this study for an additional 24 weeks from administration of the last dose of study drug.

Conditions

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Heterozygous Familial Hypercholesterolemia Coronary Artery Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Mipomersen

Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Group Type EXPERIMENTAL

mipomersen sodium

Intervention Type DRUG

200 mg /mL

Placebo

Participants received a placebo subcutaneous injection once a week for 26 weeks.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

1 mL matching placebo

Interventions

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mipomersen sodium

200 mg /mL

Intervention Type DRUG

placebo

1 mL matching placebo

Intervention Type DRUG

Other Intervention Names

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ISIS 301012 Kynamro™

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of Heterozygous Familial Hypercholesterolemia (HeFH)
* Diagnosis of Coronary Artery Disease (CAD)
* Stable lipid-lowering therapy for 12 weeks
* On maximally tolerated statin therapy with at least 1 statin at a dose greater than zero, per Investigator judgment
* Stable low-fat diet for 8 weeks
* Stable weight for 6 weeks

Exclusion Criteria

* Significant health problems in recent past including heart attack, stroke, coronary syndrome, unstable angina, heart failure, significant arrhythmia, orthostatic hypotension, uncontrolled hypertension, blood disorders, liver disease, cancer, or digestive problems
* Receiving apheresis treatment or last apheresis treatment within 8 weeks
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role collaborator

Kastle Therapeutics, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Monitor

Role: STUDY_DIRECTOR

Genzyme, a Sanofi Company

Locations

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La Jolla, California, United States

Site Status

Los Angeles, California, United States

Site Status

Mission Viejo, California, United States

Site Status

Newport Beach, California, United States

Site Status

Santa Ana, California, United States

Site Status

Thousand Oaks, California, United States

Site Status

Bridgeport, Connecticut, United States

Site Status

Melbourne, Florida, United States

Site Status

Pensacola, Florida, United States

Site Status

Chicago, Illinois, United States

Site Status

Naperville, Illinois, United States

Site Status

Kansas City, Kansas, United States

Site Status

Biddeford, Maine, United States

Site Status

Scarborough, Maine, United States

Site Status

Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

Site Status

St Louis, Missouri, United States

Site Status

Las Vegas, Nevada, United States

Site Status

Concord, New Hampshire, United States

Site Status

New York, New York, United States

Site Status

The Rogosin Institute Comprehensive Lipid Control Center

New York, New York, United States

Site Status

Charlotte, North Carolina, United States

Site Status

Charlotte, North Carolina, United States

Site Status

Durham, North Carolina, United States

Site Status

Cincinnati, Ohio, United States

Site Status

ResEvo, LLC

Cuyahoga Falls, Ohio, United States

Site Status

Franklin, Ohio, United States

Site Status

Oklahoma City, Oklahoma, United States

Site Status

Portland, Oregon, United States

Site Status

Nashville, Tennessee, United States

Site Status

Dallas, Texas, United States

Site Status

Dallas, Texas, United States

Site Status

Grapevine, Texas, United States

Site Status

Houston, Texas, United States

Site Status

San Antonio, Texas, United States

Site Status

Salt Lake City, Utah, United States

Site Status

Seattle, Washington, United States

Site Status

Calgary, Alberta, Canada

Site Status

Vancouver, British Columbia, Canada

Site Status

Winnipeg, Manitoba, Canada

Site Status

London, Ontario, Canada

Site Status

Toronto, Ontario, Canada

Site Status

Toronto, Ontario, Canada

Site Status

Chicoutimi, Quebec, Canada

Site Status

Montreal, Quebec, Canada

Site Status

Montreal, Quebec, Canada

Site Status

Saint Foy, Quebec, Canada

Site Status

Sherbrooke, Quebec, Canada

Site Status

Countries

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United States Canada

References

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Stein EA, Dufour R, Gagne C, Gaudet D, East C, Donovan JM, Chin W, Tribble DL, McGowan M. Apolipoprotein B synthesis inhibition with mipomersen in heterozygous familial hypercholesterolemia: results of a randomized, double-blind, placebo-controlled trial to assess efficacy and safety as add-on therapy in patients with coronary artery disease. Circulation. 2012 Nov 6;126(19):2283-92. doi: 10.1161/CIRCULATIONAHA.112.104125. Epub 2012 Oct 11.

Reference Type RESULT
PMID: 23060426 (View on PubMed)

Duell PB, Santos RD, Kirwan BA, Witztum JL, Tsimikas S, Kastelein JJP. Long-term mipomersen treatment is associated with a reduction in cardiovascular events in patients with familial hypercholesterolemia. J Clin Lipidol. 2016 Jul-Aug;10(4):1011-1021. doi: 10.1016/j.jacl.2016.04.013. Epub 2016 May 9.

Reference Type DERIVED
PMID: 27578134 (View on PubMed)

Santos RD, Raal FJ, Catapano AL, Witztum JL, Steinhagen-Thiessen E, Tsimikas S. Mipomersen, an antisense oligonucleotide to apolipoprotein B-100, reduces lipoprotein(a) in various populations with hypercholesterolemia: results of 4 phase III trials. Arterioscler Thromb Vasc Biol. 2015 Mar;35(3):689-99. doi: 10.1161/ATVBAHA.114.304549. Epub 2015 Jan 22.

Reference Type DERIVED
PMID: 25614280 (View on PubMed)

Other Identifiers

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301012-CS7

Identifier Type: -

Identifier Source: org_study_id

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