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HypercholesterolemiaPhase 3NCT00794664

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

A Phase 3 study testing Mipomersen in people with Hypercholesterolemia and Coronary Heart Disease, run by Kastle Therapeutics, LLC at 27 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hypercholesterolemia, Coronary Heart Disease
What is being tested?
Mipomersen
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
58 participants
Where
27 sitesin 6 countries
Study dates
Jan 2009to Oct 2010
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

27 sites in 6 countries.

27 sites in 6 countries

United States9 sites

  • Study site

    Aiken, South Carolina, 29801

  • Study site

    Atlanta, Georgia, 30338

  • Study site

    Boston, Massachusetts, 02114

  • Study site

    Cincinnati, Ohio, 45212

  • Study site

    Concord, New Hampshire, 03301

  • Study site

    Jupiter, Florida, 33458

  • Study site

    Kansas City, Kansas, 66160

  • Study site

    St Louis, Missouri, 63104

  • Study site

    Winter Park, Florida, 32792

Other trials in United States

Czechia4 sites

  • Study site

    Hardec Kralove, 500 05

  • Study site

    Pilsen, 305 99

  • Study site

    Prague, 128 08

  • Study site

    Uherské Hradiště, 686 68

Other trials in Czechia

Germany4 sites

  • Study site

    Berlin, 13353

  • Study site

    Freiburg im Breisgau, 79106

  • Study site

    Heidelberg, 69120

  • Study site

    Koln (Lindenthal), 50937

Other trials in Germany

South Africa4 sites

  • Study site

    Cape Town, 7500

  • Study site

    Cape Town, 7925

  • Study site

    Gauteng, 0157

  • Study site

    Pretoria, 0002

Other trials in South Africa

Canada3 sites

  • Study site

    Chicoutimi, Quebec, G7H 5H6

  • Study site

    Montreal, Quebec, H1T 1C8

  • Study site

    Winnipeg, Manitoba, R3A 1M5

Other trials in Canada

United Kingdom3 sites

  • Study site

    Guildford, Surrey, GU2 7XX

  • Study site

    London, SE1 7EH

  • Study site

    Manchester, MI3 9WL

Other trials in United Kingdom

About this study

Official title: A Prospective Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Mipomersen in Patients With Severe Hypercholesterolemia on a Maximally Tolerated Lipid-Lowering Regimen and Who Are Not on Apheresis

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.

Read the detailed description

Hypercholesterolemia is characterized by markedly elevated low density lipoproteins (LDL). Elevated LDL is a major risk factor for coronary heart disease (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 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. The purpose of this study is to determine whether mipomersen safely and effectively lowers LDL-C in severely hypercholesterolemic patients who are on a maximally tolerated lipid-lowering regimen and who are not on apheresis.

Being tested
Mipomersen, Placebo
Medical subject headings
Hypercholesterolemia, Coronary Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MipomersenDrug

    Also called ISIS 301012, Mipomersen sodium, Kynamro™

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

  • PlaceboDrug

    1 mL weekly subcutaneous injections for 26 weeks

Study groups in NCT00794664
Study groupRoleWhat they receive
PlaceboPlacebo comparatorWeekly subcutaneous injections for 26 weeks
Receives: Drug: Placebo
MipomersenExperimental200 mg weekly subcutaneous injections for 26 weeks
Receives: Drug: Mipomersen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

    Measured: 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)

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

    Apo-B was measured in mg/dL. Samples were taken following an overnight fast. 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.

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

  2. Apo-B 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.

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

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

    Total cholesterol was measured in mg/dL. Samples were taken following an overnight fast. 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.

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

  4. Total Cholesterol 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.

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

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

    Non-HDL-C was measured in mg/dL. Samples were taken following an overnight fast. 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.

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

  6. Non-HDL-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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Nov 2008 (estimated)
  2. Study startJan 2009
  3. Primary completionMay 2010
  4. Study completionOct 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00794664
Sponsor's protocol ID
MIPO3500108
Other IDs
2008-006020-53, 2008
Status last verified
Aug 2016
First submitted
19 Nov 2008
Last updated
9 Sep 2016
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 23152839

  • 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.

    PubMed 27578134

  • 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.

    PubMed 25614280

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Mipomersen in people with Hypercholesterolemia and Coronary Heart Disease, run by Kastle Therapeutics, LLC at 27 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in United States, Czechia, Germany, South Africa, Canada and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Mar 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Primary Efficacy Time Point (time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00794664, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2016.

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