Safety and Efficacy of Mipomersen (ISIS 301012) As Add-on Therapy in High Risk Hypercholesterolemic Patients

NCT ID: NCT00770146

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

158 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-11-30

Study Completion Date

2010-10-31

Brief Summary

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The purpose of this study is to evaluate the safety and efficacy of dosing with mipomersen for 26 weeks in patients with high cholesterol who are on a maximally tolerated dose of statin and who have a diagnosis that puts them at least at high risk of coronary heart disease (CHD).

Detailed Description

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Hypercholesterolemia is characterized by markedly elevated low density lipoproteins (LDL). Elevated LDL is a major risk factor for CHD.

Mipomersen 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 (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 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 patients with high cholesterol who are at high risk for CHD and who are already on the maximally tolerated dose of statin.

This study consisted of a 26-week treatment period and a 24-week post-treatment follow-up period. Participants who finished treatment or who discontinued prematurely from the study for any reason were assessed for safety for 24 weeks after the last study drug dose.

Conditions

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Hypercholesterolemia Coronary Heart 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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Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

1 mL matching placebo (i.e., vehicle consisting of 9 mg of sodium chloride, 0.004 mg of riboflavin, filled to 1 mL with water).

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

Interventions

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Mipomersen sodium

200 mg/mL

Intervention Type DRUG

Placebo

1 mL matching placebo (i.e., vehicle consisting of 9 mg of sodium chloride, 0.004 mg of riboflavin, filled to 1 mL with water).

Intervention Type DRUG

Other Intervention Names

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ISIS 301012 Kynamro™

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of hypercholesterolemia (LDL-C ≥ 100 mg/dL)
* At high risk of CHD
* On stable, maximally tolerated statin therapy for 8 weeks
* On stable, low fat diet for 12 weeks
* Stable weight for 6 weeks

Exclusion Criteria

* Significant health problems in the recent past including heart attack, stroke, coronary syndrome, unstable angina, heart failure, significant arrhythmia, hypertension, liver disease, cancer, type I diabetes.
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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Birmingham, Alabama, United States

Site Status

Birmingham, Alabama, United States

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Huntsville, Alabama, United States

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Muscle Shoals, Alabama, United States

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Litchfield Park, Arizona, United States

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Beverly Hills, California, United States

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Escondido, California, United States

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Los Angeles, California, United States

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Mission Viejo, California, United States

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Newport Beach, California, United States

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San Diego, California, United States

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Santa Rosa, California, United States

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Thousand Oaks, California, United States

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Westlake Village, California, United States

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Aventura, Florida, United States

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Inverness, Florida, United States

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Jacksonville, Florida, United States

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Longwood, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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New Port Richey, Florida, United States

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Pembroke Pines, Florida, United States

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Pensacola, Florida, United States

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Ponte Verda, Florida, United States

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Port Orange, Florida, United States

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Sandy Springs, Georgia, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Bloomingtom, Indiana, United States

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Evansville, Indiana, United States

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Indianapolis, Indiana, United States

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Indianapolis, Indiana, United States

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Louisville, Kentucky, United States

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Baltimore, Maryland, United States

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Brockton, Massachusetts, United States

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New Bedford, Massachusetts, United States

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Edina, Minnesota, United States

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Kansas City, Missouri, United States

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Berlin, New Jersey, United States

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Johnson City, New York, United States

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Charlotte, North Carolina, United States

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Greenville, North Carolina, United States

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Wilson, North Carolina, United States

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Cincinnati, Ohio, United States

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Mentor, Ohio, United States

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Norman, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Portland, Oregon, United States

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Lansdale, Pennsylvania, United States

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Murrells Inlet, South Carolina, United States

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Simpsonville, South Carolina, United States

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Spartanburg, South Carolina, United States

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Rapid City, South Dakota, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Grapevine, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Olympia, Washington, United States

Site Status

Countries

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United States

References

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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)

Thomas GS, Cromwell WC, Ali S, Chin W, Flaim JD, Davidson M. Mipomersen, an apolipoprotein B synthesis inhibitor, reduces atherogenic lipoproteins in patients with severe hypercholesterolemia at high cardiovascular risk: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol. 2013 Dec 10;62(23):2178-84. doi: 10.1016/j.jacc.2013.07.081. Epub 2013 Sep 4.

Reference Type DERIVED
PMID: 24013058 (View on PubMed)

Other Identifiers

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301012-CS12

Identifier Type: -

Identifier Source: org_study_id

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