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

NCT00706849 | Completed Phase 3 Results DMC

• 1 other identifier: 301012-CS7
• Study Type: interventional
• Target: 124
• Locations: 2 countries
• Sites: 48

Brief Summary

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).

Conditions

Heterozygous Familial Hypercholesterolemia; Coronary Artery Disease

Keywords

familial hypercholesterolemia

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. For patients with triglycerides \<400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides ≥400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. 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).

• LDL Cholesterol 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 Lipoprotein (a) 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)

Mipomersen

EXPERIMENTAL

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

Drug: mipomersen sodium

Placebo

PLACEBO COMPARATOR

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

Drug: placebo

Interventions

mipomersen sodium DRUG

200 mg /mL

Also known as: ISIS 301012, Kynamro™

Mipomersen

placebo DRUG

1 mL matching placebo

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (48)

Unknown Facility

La Jolla, California, 92093, United States

Location

Unknown Facility

Los Angeles, California, 90048, United States

Location

Unknown Facility

Mission Viejo, California, 92691, United States

Location

Unknown Facility

Newport Beach, California, 92260, United States

Location

Unknown Facility

Santa Ana, California, 92705, United States

Location

Unknown Facility

Thousand Oaks, California, 91360, United States

Location

Unknown Facility

Bridgeport, Connecticut, 06606, United States

Location

Unknown Facility

Melbourne, Florida, 32901, United States

Location

Unknown Facility

Pensacola, Florida, 32514, United States

Location

Unknown Facility

Chicago, Illinois, 60610, United States

Location

Unknown Facility

Naperville, Illinois, 60540, United States

Location

Unknown Facility

Kansas City, Kansas, 66160, United States

Location

Unknown Facility

Biddeford, Maine, 04005, United States

Location

Unknown Facility

Scarborough, Maine, 04074, United States

Location

Unknown Facility

Boston, Massachusetts, 02114, United States

Location

Unknown Facility

Ann Arbor, Michigan, 48109-5853, United States

Location

Unknown Facility

St Louis, Missouri, 63110, United States

Location

Unknown Facility

Las Vegas, Nevada, 89144, United States

Location

Unknown Facility

Concord, New Hampshire, 03301, United States

Location

Unknown Facility

New York, New York, 10032, United States

Location

The Rogosin Institute Comprehensive Lipid Control Center

New York, New York, 10065, United States

Location

Unknown Facility

Charlotte, North Carolina, 28204, United States

Location

Unknown Facility

Charlotte, North Carolina, 28211, United States

Location

Unknown Facility

Durham, North Carolina, 27710, United States

Location

Unknown Facility

Cincinnati, Ohio, 45212, United States

Location

ResEvo, LLC

Cuyahoga Falls, Ohio, 44223, United States

Location

Unknown Facility

Franklin, Ohio, 45005, United States

Location

Unknown Facility

Oklahoma City, Oklahoma, 73120, United States

Location

Unknown Facility

Portland, Oregon, 97239, United States

Location

Unknown Facility

Nashville, Tennessee, 37232, United States

Location

Unknown Facility

Dallas, Texas, 75220, United States

Location

Unknown Facility

Dallas, Texas, 75226, United States

Location

Unknown Facility

Grapevine, Texas, 76051, United States

Location

Unknown Facility

Houston, Texas, 77093, United States

Location

Unknown Facility

San Antonio, Texas, 78229, United States

Location

Unknown Facility

Salt Lake City, Utah, 84108, United States

Location

Unknown Facility

Seattle, Washington, 98104, United States

Location

Unknown Facility

Calgary, Alberta, T2E 7C5, Canada

Location

Unknown Facility

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Unknown Facility

Winnipeg, Manitoba, R3A 1R9, Canada

Location

Unknown Facility

London, Ontario, N6A 5K8, Canada

Location

Unknown Facility

Toronto, Ontario, M5C 2T2, Canada

Location

Unknown Facility

Toronto, Ontario, M5G 2C4, Canada

Location

Unknown Facility

Chicoutimi, Quebec, G7H 5H6, Canada

Location

Unknown Facility

Montreal, Quebec, H1T 1C8, Canada

Location

Unknown Facility

Montreal, Quebec, H2W 1R7, Canada

Location

Unknown Facility

Saint Foy, Quebec, G1V 4M6, Canada

Location

Unknown Facility

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Related Publications (3)

• 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.

  PMID: 23060426 RESULT

• 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.

  PMID: 27578134 DERIVED

• 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

MeSH Terms

Conditions

Coronary Artery Disease; Hyperlipoproteinemia Type II

Interventions

mipomersen

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic 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: June 26, 2008
• First Posted: June 30, 2008
• Study Start: July 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: May 1, 2010
• Last Updated: September 9, 2016
• Results First Posted: March 21, 2013

Record last verified: 2016-08

Locations

US (37); CA (11)