Lipid Metabolism, Inborn ErrorsPhase 3NCT00694109

An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia

A Phase 3 study testing Mipomersen Sodium in people with Lipid Metabolism, Inborn Errors and Hypercholesterolemia, Autosomal Dominant, run by Kastle Therapeutics, LLC at 33 sites in 7 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

To evaluate the safety and efficacy of extended dosing with mipomersen (ISIS 301012) in participants with familial hypercholesterolemia or severe hypercholesterolemia on lipid-lowering therapy who had completed either the 301012-CS5 (NCT00607373), 301012-CS7 (NCT00706849), 301012-CS17 (NCT00477594) or MIPO3500108… Read more about this study

Who is it for?: Ages 12 years and older
Conditions the study is for: Lipid Metabolism, Inborn Errors, Hypercholesterolemia, Autosomal Dominant, Hyperlipidemias
What is being tested?: Mipomersen Sodium
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 144 participants
Where: 33 sitesin 7 countries
Study dates: Apr 2008to Sep 2014
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 12 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Satisfactory completion of dosing in their initial study (Protocol 301012-CS5 [NCT00607373], 301012-CS7 [NCT00706849], 301012-CS17 [NCT00477594], or MIPO3500108 [NCT00794664])

Who cannot join

Had any new condition or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study

Trial locations and contacts

33 sites in 7 countries.

Country

City, postcode or hospital

33 sites in 7 countries

United States20 sites

Study site
Biddeford, Maine, 04005
Study site
Boston, Massachusetts, 02114
Study site
Bridgeport, Connecticut, 06606
Study site
Charlotte, North Carolina, 28204
Study site
Chicago, Illinois, 60654
Study site
Cincinnati, Ohio, 45212
Study site
Concord, New Hampshire, 03301
Study site
Dallas, Texas, 75226
Study site
Durham, North Carolina, 27710
Study site
Franklin, Ohio, 45005
Study site
Kansas City, Kansas, 66160
Study site
Melbourne, Florida, 32901
Study site
Mission Viejo, California, 92691
Study site
Nashville, Tennessee, 37232
Study site
New York, New York, 10032
Study site
Newport Beach, California, 92660
Study site
Portland, Oregon, 97239
Study site
Seattle, Washington, 98104
Study site
St Louis, Missouri, 63110
Study site
Winter Park, Florida, 32792

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Canada7 sites

Study site
Chicoutimi, Quebec, G7H 5H6
Study site
London, Ontario, N6A 5K8
Study site
Montreal, Quebec, H1T 1C8
Study site
Montreal, Quebec, H2W 1R7
Study site
Québec, Quebec, G1V 4M6
Study site
Sherbrooke, Quebec, J1H 5N4
Study site
Winnipeg, Manitoba, R3A 1M5

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South Africa2 sites

Study site
Observatory, South Africa, 7925
Study site
Parktown, South Africa, 2193

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Brazil1 site

Study site
São Paulo, São Paulo

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Singapore1 site

Study site
Singapore, 168752

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Taiwan1 site

Study site
Taipei, Taiwan, 11217

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United Kingdom1 site

Study site
London, United Kingdom, WC1N 3BG

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About this study

Official title: An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia

Read the detailed description

All familial hypercholesterolemia (FH) or severe hypercholesterolemia participants who had tolerated the treatment regimen in Protocol 301012-CS5 (NCT00607373), 301012-CS7 (NCT00706849) or MIPO3500108 (NCT00794664) and satisfactorily completed the study through to Week 28 were eligible for participation in this open label treatment extension study for up to 4 years or until mipomersen was commercially available, whichever comes first. Consenting participants who had tolerated mipomersen and satisfactorily completed 301012-CS17 (NCT00477594) through Year 3 may also enroll for up to an additional 2 years of treatment in this study or until mipomersen was commercially available, whichever comes first. All participants, who entered the study, received 200 mg mipomersen (ISIS 301012) subcutaneously (s.c.) every week, including those who were randomized to placebo in their initial study. Participants who were originally enrolled in Protocol 301012-CS5 (NCT00607373) and weighed <50 kg received 160 mg every week. Dose adjustments (70 mg injections administered three times per week, on separate days) were allowed for participants who were not tolerating or who had previous issues with tolerating the once a week injections due to injection site reactions (ISRs) or flu-like symptoms. Study visits and clinical lab assessments including hematology with differential, chemistry, serum lipid panel (total cholesterol, LDL-C, very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB), apoA-1, triglycerides (TG) and Lp(a), and urinalysis was to be performed every 4-10 weeks during the treatment period. Plasma trough mipomersen (ISIS 301012) levels was to be measured to estimate exposure. Participants who completed dosing or who discontinued prematurely from the study for any reason was followed for safety for 24 weeks (safety follow-up period) after their last dose of mipomersen (ISIS 301012) or longer in the case of a significant adverse events (AE) or abnormal biochemical or clinical finding. Participants were required to return to the study center for clinical evaluation and clinical laboratory tests every 8 weeks during the safety follow-up period.

Conditions: Lipid Metabolism, Inborn Errors, Hypercholesterolemia, Autosomal Dominant, Hyperlipidemias, Metabolic Diseases, Hyperlipoproteinemia Type II, Metabolism, Inborn Errors
Being tested: Mipomersen Sodium
Keywords: Familial Hypercholesterolemia, FH, Heterozygous Familial Hypercholesterolemia, HeFH, Homozygous Familial Hypercholesterolemia, HoFH
Medical subject headings: Lipid Metabolism, Inborn Errors, Hyperlipoproteinemia Type II, Hyperlipidemias, Metabolic Diseases, Metabolism, Inborn Errors, Genetic Diseases, Inborn, Infant, Newborn, Diseases, Congenital Abnormalities

What participants receive

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

Mipomersen SodiumDrug
Also called ISIS 301012, Kynamro®
Subcutaneous injection as a single injection directly into the abdomen, thigh, or outer area of the upper arm.

Study groups in NCT00694109
Study group	Role	What they receive
Mipomersen	Experimental	Mipomersen Sodium once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment. Receives: Drug: Mipomersen Sodium

What is being measured

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

Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in Apolipoprotein B (Apo B)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in Total Cholesterol
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)

Secondary outcomes (17)

Percent Change From Baseline in Triglycerides
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in Lipoprotein (a)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in LDL Particles' Size (Total)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in LDL Particles' Size (Large)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in LDL Particles' Size (Medium)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in LDL Particles' Size (Small)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in LDL Particles' Size (Very Small)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in HDL Particles' Size (Large)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in HDL Particles' Size (Medium)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in HDL Particles' Size (Small)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in Intermediate Density Lipoprotein Particles' Size
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Particles' Size (Large) and Chylomicron Particles' Size
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in VLDL Particles' Size (Medium)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in VLDL Particles' Size (Small)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in Total VLDL Particles' Size and Chylomicron Particles' Size
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Change From Baseline in C-Reactive Protein
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in Apolipoprotein A-1
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Measured: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)

Timeline

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

Apr 2008Sep 2014

First posted10 Jun 2008 (estimated)
Study startApr 2008
Primary completionSep 2014
Study completionSep 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Lipid Metabolism, Inborn ErrorsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 144 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00694109
Sponsor's protocol ID: 301012-CS6
Other IDs: 2005-003450-10, 2005
Status last verified: Aug 2016
First submitted: 5 Jun 2008
Last updated: 9 Sep 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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, Duell PB, East C, Guyton JR, Moriarty PM, Chin W, Mittleman RS. Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension. Eur Heart J. 2015 Mar 1;36(9):566-75. doi: 10.1093/eurheartj/eht549. Epub 2013 Dec 23.
PubMed 24366918

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 9 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia
ClinicalTrials.gov ID: NCT00694109
Acronym / sponsor ID: 301012-CS6
Conditions: Lipid Metabolism, Inborn Errors, Hypercholesterolemia, Autosomal Dominant, Hyperlipidemias, Metabolic Diseases, Hyperlipoproteinemia Type II, Metabolism, Inborn Errors
Keywords: Familial Hypercholesterolemia, FH, Heterozygous Familial Hypercholesterolemia, HeFH, Homozygous Familial Hypercholesterolemia, HoFH
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 144 participants (actual)
Lead sponsor: Kastle Therapeutics, LLCIndustry (pharma, biotech, devices)
Collaborators: Ionis Pharmaceuticals, Inc.
Study start: Apr 2008
Primary completion: Sep 2014 (actual)
Study completion: Sep 2014 (actual)
First posted: 10 Jun 2008 (estimated)
Results: Posted 21 Dec 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Mipomersen	Experimental	Drug: Mipomersen SodiumMipomersen Sodium once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.

Who may qualify

Ages: 12 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (1 listed)

Satisfactory completion of dosing in their initial study (Protocol 301012-CS5 [NCT00607373], 301012-CS7 [NCT00706849], 301012-CS17 [NCT00477594], or MIPO3500108 [NCT00794664])

Key exclusion criteria (1 listed)

Had any new condition or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Mipomersen SodiumAlso: ISIS 301012, Kynamro®Subcutaneous injection as a single injection directly into the abdomen, thigh, or outer area of the upper arm.	Drug	Mipomersen

Primary outcome

Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)
Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Percent Change From Baseline in Apolipoprotein B (Apo B)
Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Percent Change From Baseline in Total Cholesterol
Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).
Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C)
Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

17 secondary outcomes

Percent Change From Baseline in Triglycerides
Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in Lipoprotein (a)
Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in LDL Particles' Size (Total)
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in LDL Particles' Size (Large)
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in LDL Particles' Size (Medium)
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in LDL Particles' Size (Small)
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in LDL Particles' Size (Very Small)
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in HDL Particles' Size (Large)
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in HDL Particles' Size (Medium)
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in HDL Particles' Size (Small)
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in Intermediate Density Lipoprotein Particles' Size
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Particles' Size (Large) and Chylomicron Particles' Size
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in VLDL Particles' Size (Medium)
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in VLDL Particles' Size (Small)
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in Total VLDL Particles' Size and Chylomicron Particles' Size
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Change From Baseline in C-Reactive Protein
Time frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years)
Percent Change From Baseline in Apolipoprotein A-1
Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)

Results and safety

Results posted to the registry on 21 Dec 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Mipomersen	142	25

Primary outcome: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)

Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years). Mean (95% Confidence Interval). Unit: percent change

Measure	Mipomersen n = 141
week 26 (n = 130)	-28.5 (-31.9 to -25.1)
week 52 (n = 111)	-27 (-31.2 to -22.8)
week 76 (n = 66)	-27.3 (-33 to -21.6)
week 104 (n = 57)	-27.9 (-33.9 to -21.8)
week 130 (n = 42)	-21.9 (-31.1 to -12.7)
week 156 (n = 30)	-21.4 (-31.2 to -11.7)
week 182 (n = 26)	-23.6 (-36.6 to -10.6)
week 208 (n = 27)	-26.3 (-36.4 to -16.2)

Population analysed: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.

Primary outcome: Percent Change From Baseline in Apolipoprotein B (Apo B)

Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years). Mean (95% Confidence Interval). Unit: percent change

Measure	Mipomersen n = 141
week 26 (n = 130)	-28.9 (-32 to -25.8)
week 52 (n = 111)	-28.1 (-32 to -24.2)
week 76 (n = 66)	-30.3 (-34.7 to -26)
week 104 (n = 57)	-31.2 (-36.5 to -25.9)
week 130 (n = 43)	-29.1 (-35.7 to -22.5)
week 156 (n = 30)	-30.2 (-38.1 to -22.2)
week 182 (n = 26)	-31.1 (-39.9 to -22.2)
week 208 (n = 27)	-33.3 (-40.8 to -25.9)

Population analysed: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.

Primary outcome: Percent Change From Baseline in Total Cholesterol

Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years). Mean (95% Confidence Interval). Unit: percent change

Measure	Mipomersen n = 141
week 26 (n = 130)	-21.7 (-24.4 to -18.9)
week 52 (n = 111)	-20.4 (-23.9 to -16.8)
week 76 (n = 66)	-20.1 (-24.6 to -15.5)
week 104 (n = 57)	-19.8 (-24.8 to -14.7)
week 130 (n = 43)	-14.9 (-22.1 to -7.8)
week 156 (n = 30)	-14.4 (-22.3 to -6.6)
week 182 (n = 26)	-14.3 (-25 to -3.5)
week 208 (n = 27)	-16.5 (-24.2 to -8.8)

Population analysed: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.

Primary outcome: Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C)

Time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years). Mean (95% Confidence Interval). Unit: percent change

Measure	Mipomersen n = 141
week 26 (n = 130)	-27.2 (-30.4 to -24.1)
week 52 (n = 111)	-25.4 (-29.5 to -21.3)
week 76 (n = 66)	-25 (-30.4 to -19.7)
week 104 (n = 57)	-26.2 (-32 to -20.4)
week 130 (n = 43)	-20.7 (-29.1 to -12.3)
week 156 (n = 30)	-20 (-29.6 to -10.3)
week 182 (n = 26)	-21.7 (-34.7 to -8.7)
week 208 (n = 27)	-23.9 (-33.7 to -14.1)

Population analysed: Analysis was performed on Safety set. Here n=participants with lipid parameter assessment at specified time.

17 secondary outcomes are reported in the full results.

Adverse events

Time frame: All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (59.7 months) regardless of seriousness or relationship to investigational product.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Mipomersen	36 of 141 (25.5%)	141 of 141 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 27578134Duell 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.
Derived from this study: PubMed 24366918Santos RD, Duell PB, East C, Guyton JR, Moriarty PM, Chin W, Mittleman RS. Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension. Eur Heart J. 2015 Mar 1;36(9):566-75. doi: 10.1093/eurheartj/eht549. Epub 2013 Dec 23.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Monitor study director

Genzyme, a Sanofi Company

33 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Mipomersen Sodium in people with Lipid Metabolism, Inborn Errors and Hypercholesterolemia, Autosomal Dominant, run by Kastle Therapeutics, LLC at 33 sites in 7 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 1 inclusion and 1 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 33 sites in United States, Canada, South Africa, Brazil, Singapore and 2 more countries. 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. 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 Dec 2015). 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) (time frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years)). The study lists 4 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 NCT00694109, which also lists 2 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.