Safety and Efficacy of Mipomersen in Patients With Severe Hypercholesterolemia on a Maximally Tolerated Lipid-Lowering Regimen and Who Are Not on Apheresis

NCT00794664 | Completed Phase 3 Results DMC

• 2 other identifiers: MIPO35001082008-006020-53
• Study Type: interventional
• Target: 58
• Locations: 6 countries
• Sites: 27

Brief Summary

The purpose of the study is to evaluate the safety and efficacy of dosing with mipomersen for 26 weeks in treating severely hypercholesterolemic patients who are on a maximally tolerated lipid-lowering regimen and who are not on apheresis.

Conditions

Hypercholesterolemia; Coronary Heart Disease

Outcome Measures

Primary Outcomes (2)

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

  LDL-C 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. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

• LDL-C at Baseline and the Primary Efficacy Time Point (PET)

  The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Secondary Outcomes (6)

• Percent Change From Baseline in Apolipoprotein B (Apo-B) at Primary Efficacy Time Point

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

• Apo-B at Baseline and the Primary Efficacy Time Point (PET)

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

• Percentage Change From Baseline in Total Cholesterol at Primary Efficacy Time Point (PET)

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

• Total Cholesterol at Baseline and the Primary Efficacy Time Point (PET)

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

• Percentage Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Primary Efficacy Time Point (PET)

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Other Outcomes (12)

• Percentage Change From Baseline in Triglycerides at Primary Efficacy Time Point (PET)

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

• Triglycerides at Baseline and the Primary Efficacy Time Point (PET)

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

• Percentage Change From Baseline in Lipoprotein(a) at Primary Efficacy Time Point (PET)

  Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Weekly subcutaneous injections for 26 weeks

Drug: Placebo

Mipomersen

EXPERIMENTAL

200 mg weekly subcutaneous injections for 26 weeks

Drug: Mipomersen

Interventions

Mipomersen DRUG

200 mg (1 mL), weekly subcutaneous injections for 26 weeks

Also known as: ISIS 301012, Mipomersen sodium, Kynamro™

Mipomersen

Placebo DRUG

1 mL weekly subcutaneous injections for 26 weeks

Placebo

Eligibility Criteria

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

You may qualify if:

• Fasting LDL-C ≥200 mg/dL (5.1 mmol/L) at screening and the presence of at least 1 of the following criteria:
• Myocardial infarction (MI)
• Percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)
• Coronary artery disease documented by angiography or any other accepted imaging technique
• Positive exercise test (≥1 mm ST-depression at maximal exercise or test terminated because of angina) or a perfusion defect (e.g., thallium or single photon emission computed tomography)
• Other clinical atherosclerotic diseases: peripheral artery disease, symptomatic carotid artery disease, abdominal aortic aneurysm
• Or, if alternative above were not met, fasting LDL-C ≥300 mg/dL (7.8 mmol/L)
• On stable, maximally tolerated statin therapy for 8 weeks
• On stable, medication from an additional class of hypolipidemic agents 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, blood disorders, liver disease, cancer, digestive disorders, Type I diabetes, or uncontrolled Type II diabetes
• Apheresis within 3 months prior to Screening or expected to start apheresis during the treatment phase

Sponsors & Collaborators

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

Study Sites (27)

Unknown Facility

Jupiter, Florida, 33458, United States

Location

Unknown Facility

Winter Park, Florida, 32792, United States

Location

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Atlanta, Georgia, 30338, United States

Location

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Kansas City, Kansas, 66160, United States

Location

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Boston, Massachusetts, 02114, United States

Location

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St Louis, Missouri, 63104, United States

Location

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Concord, New Hampshire, 03301, United States

Location

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Cincinnati, Ohio, 45212, United States

Location

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Aiken, South Carolina, 29801, United States

Location

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Winnipeg, Manitoba, R3A 1M5, Canada

Location

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Chicoutimi, Quebec, G7H 5H6, Canada

Location

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Montreal, Quebec, H1T 1C8, Canada

Location

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Hardec Kralove, 500 05, Czechia

Location

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Pilsen, 305 99, Czechia

Location

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Prague, 128 08, Czechia

Location

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Uherské Hradiště, 686 68, Czechia

Location

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Berlin, 13353, Germany

Location

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Freiburg im Breisgau, 79106, Germany

Location

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Heidelberg, 69120, Germany

Location

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Koln (Lindenthal), 50937, Germany

Location

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Cape Town, 7500, South Africa

Location

Unknown Facility

Cape Town, 7925, South Africa

Location

Unknown Facility

Gauteng, 0157, South Africa

Location

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Pretoria, 0002, South Africa

Location

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Guildford, Surrey, GU2 7XX, United Kingdom

Location

Unknown Facility

London, SE1 7EH, United Kingdom

Location

Unknown Facility

Manchester, MI3 9WL, United Kingdom

Location

Related Publications (3)

• McGowan MP, Tardif JC, Ceska R, Burgess LJ, Soran H, Gouni-Berthold I, Wagener G, Chasan-Taber S. Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy. PLoS One. 2012;7(11):e49006. doi: 10.1371/journal.pone.0049006. Epub 2012 Nov 13.

  PMID: 23152839 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

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: November 19, 2008
• First Posted: November 20, 2008
• Study Start: January 1, 2009
• Primary Completion: May 1, 2010
• Study Completion: October 1, 2010
• Last Updated: September 9, 2016
• Results First Posted: March 21, 2013

Record last verified: 2016-08

Locations

CZ (4); ZA (4); GB (3); US (9); CA (3); DE (4)