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

NCT00770146 | Completed Phase 3 Results DMC

• 1 other identifier: 301012-CS12
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 62

Brief Summary

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).

Conditions

Hypercholesterolemia; Coronary Heart Disease

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the Primary Efficacy Time Point

  LDL cholesterol was measured in mg/dL. Samples were taken following an overnight fast. LDL-C was obtained using Friedewald's calculation for patients with triglycerides ≤400 mg/dL and was directly measured by the central laboratory using ultracentrifugation for patients with triglycerides \>400 mg/dL. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

• Low-density Lipoprotein Cholesterol (LDL-C) at Baseline and at the Primary Efficacy Time Point

  The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

Secondary Outcomes (6)

• Percent Change From Baseline in Apolipoprotein B at the Primary Efficacy Time Point

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

• Apolipoprotein B at Baseline and at the Primary Efficacy Time Point

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

• Percent Change From Baseline in Total Cholesterol at the Primary Efficacy Time Point

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

• Total Cholesterol at Baseline and at the Primary Efficacy Time Point

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

• Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol at the Primary Efficacy Time Point

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

Other Outcomes (12)

• Percent Change From Baseline in Triglycerides at the Primary Efficacy Time Point

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

• Triglycerides at Baseline and at the Primary Efficacy Time Point

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

• Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at the Primary Efficacy Time Point

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Mipomersen

EXPERIMENTAL

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

Drug: Mipomersen sodium

Interventions

Mipomersen sodium DRUG

200 mg/mL

Also known as: ISIS 301012, Kynamro™

Mipomersen

Placebo 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).

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kastle Therapeutics, LLC: lead
• Ionis Pharmaceuticals, Inc.: collaborator

Study Sites (62)

Unknown Facility

Birmingham, Alabama, 35209, United States

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Birmingham, Alabama, 35294, United States

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Huntsville, Alabama, 35801, United States

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Muscle Shoals, Alabama, 35662, United States

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Litchfield Park, Arizona, 85340, United States

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Beverly Hills, California, 90211, United States

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Escondido, California, 92025, United States

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Los Angeles, California, 90025, United States

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Mission Viejo, California, 92691, United States

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Newport Beach, California, 92660, United States

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San Diego, California, 92117, United States

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Santa Rosa, California, 95405, United States

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Thousand Oaks, California, 91360, United States

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Westlake Village, California, 91361, United States

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Aventura, Florida, 33180, United States

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Inverness, Florida, 34452, United States

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Jacksonville, Florida, 32216, United States

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Longwood, Florida, 32779, United States

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Miami, Florida, 33143, United States

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Miami, Florida, 33169, United States

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New Port Richey, Florida, 34652, United States

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Pembroke Pines, Florida, 33026, United States

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Pensacola, Florida, 32514, United States

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Ponte Verda, Florida, 32081, United States

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Port Orange, Florida, 32127, United States

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Sandy Springs, Georgia, 30328, United States

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Chicago, Illinois, 60607, United States

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Chicago, Illinois, 60624, United States

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Chicago, Illinois, 60654, United States

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Bloomingtom, Indiana, 47403, United States

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Evansville, Indiana, 47714, United States

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Indianapolis, Indiana, 46254, United States

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Indianapolis, Indiana, 46260, United States

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Louisville, Kentucky, 40213, United States

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Baltimore, Maryland, 21209, United States

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Brockton, Massachusetts, 02301, United States

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New Bedford, Massachusetts, 02740, United States

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Edina, Minnesota, 55435, United States

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Kansas City, Missouri, 64111, United States

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Berlin, New Jersey, 08009, United States

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Johnson City, New York, 13790, United States

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Charlotte, North Carolina, 28204, United States

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Greenville, North Carolina, 27834, United States

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Wilson, North Carolina, 27893, United States

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Cincinnati, Ohio, 45219, United States

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Mentor, Ohio, 44060, United States

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Norman, Oklahoma, 73069, United States

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Tulsa, Oklahoma, 74136, United States

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Portland, Oregon, 97239, United States

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Lansdale, Pennsylvania, 19446, United States

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Murrells Inlet, South Carolina, 29576, United States

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Simpsonville, South Carolina, 29681, United States

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Spartanburg, South Carolina, 29303, United States

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Rapid City, South Dakota, 57702, United States

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Dallas, Texas, 75220, United States

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Dallas, Texas, 75251, United States

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Grapevine, Texas, 76051, United States

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Houston, Texas, 77030, United States

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Houston, Texas, 77074, United States

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Houston, Texas, 77093, United States

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San Antonio, Texas, 78229, United States

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Olympia, Washington, 98502, United States

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Related Publications (2)

• 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.

  PMID: 25614280 DERIVED

• 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.

  PMID: 24013058 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia; Coronary Disease

Interventions

mipomersen

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Results Point of Contact

• Title: Genzyme Medical Information
• Organization: Genzyme Corporation

617-252-7832

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2008
• First Posted: October 9, 2008
• Study Start: November 1, 2008
• Primary Completion: May 1, 2010
• Study Completion: October 1, 2010
• Last Updated: September 9, 2016
• Results First Posted: March 20, 2013

Record last verified: 2016-08

Locations

US (62)