HypercholesterolemiaPhase 3NCT00770146
Safety and Efficacy of Mipomersen (ISIS 301012) As Add-on Therapy in High Risk Hypercholesterolemic Patients
A Phase 3 study testing Mipomersen sodium in people with Hypercholesterolemia and Coronary Heart Disease, run by Kastle Therapeutics, LLC at 62 sites in United States.
Trial 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). 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 sodium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 158 participants
- Where
- 62 sitesUnited States
- Study dates
- Nov 2008to 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
- 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
Who cannot join
- 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.
Trial locations and contacts
62 sites in 1 country.
62 sites in 1 country
United States62 sites
Study site
Aventura, Florida, 33180
Study site
Baltimore, Maryland, 21209
Study site
Berlin, New Jersey, 08009
Study site
Beverly Hills, California, 90211
Study site
Birmingham, Alabama, 35209
Study site
Birmingham, Alabama, 35294
Study site
Bloomingtom, Indiana, 47403
Study site
Brockton, Massachusetts, 02301
Study site
Charlotte, North Carolina, 28204
Study site
Chicago, Illinois, 60607
Study site
Chicago, Illinois, 60624
Study site
Chicago, Illinois, 60654
Study site
Cincinnati, Ohio, 45219
Study site
Dallas, Texas, 75220
Study site
Dallas, Texas, 75251
Study site
Edina, Minnesota, 55435
Study site
Escondido, California, 92025
Study site
Evansville, Indiana, 47714
Study site
Grapevine, Texas, 76051
Study site
Greenville, North Carolina, 27834
Study site
Houston, Texas, 77030
Study site
Houston, Texas, 77074
Study site
Houston, Texas, 77093
Study site
Huntsville, Alabama, 35801
Study site
Indianapolis, Indiana, 46254
Study site
Indianapolis, Indiana, 46260
Study site
Inverness, Florida, 34452
Study site
Jacksonville, Florida, 32216
Study site
Johnson City, New York, 13790
Study site
Kansas City, Missouri, 64111
Study site
Lansdale, Pennsylvania, 19446
Study site
Litchfield Park, Arizona, 85340
Study site
Longwood, Florida, 32779
Study site
Los Angeles, California, 90025
Study site
Louisville, Kentucky, 40213
Study site
Mentor, Ohio, 44060
Study site
Miami, Florida, 33143
Study site
Miami, Florida, 33169
Study site
Mission Viejo, California, 92691
Study site
Murrells Inlet, South Carolina, 29576
Study site
Muscle Shoals, Alabama, 35662
Study site
New Bedford, Massachusetts, 02740
Study site
New Port Richey, Florida, 34652
Study site
Newport Beach, California, 92660
Study site
Norman, Oklahoma, 73069
Study site
Olympia, Washington, 98502
Study site
Pembroke Pines, Florida, 33026
Study site
Pensacola, Florida, 32514
Study site
Ponte Verda, Florida, 32081
Study site
Port Orange, Florida, 32127
Study site
Portland, Oregon, 97239
Study site
Rapid City, South Dakota, 57702
Study site
San Antonio, Texas, 78229
Study site
San Diego, California, 92117
Study site
Sandy Springs, Georgia, 30328
Study site
Santa Rosa, California, 95405
Study site
Simpsonville, South Carolina, 29681
Study site
Spartanburg, South Carolina, 29303
Study site
Thousand Oaks, California, 91360
Study site
Tulsa, Oklahoma, 74136
Study site
Westlake Village, California, 91361
Study site
Wilson, North Carolina, 27893
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) as Add-on Therapy in High Risk Hypercholesterolemic Patients
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).
Read the detailed description
Hypercholesterolemia is characterized by markedly elevated low density lipoproteins (LDL). Elevated LDL is a major risk factor for 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 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 patients with high cholesterol who are at high risk for CHD and who are already on the maximally tolerated dose of statin.
This study consisted of a 26-week treatment period and a 24-week post-treatment follow-up period. Participants who finished treatment or who discontinued prematurely from the study for any reason were assessed for safety for 24 weeks after the last study drug dose.
- Conditions
- Hypercholesterolemia, Coronary Heart Disease
- Being tested
- Mipomersen sodium, 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.
Mipomersen sodiumDrug
Also called ISIS 301012, Kynamro™
200 mg/mL
PlaceboDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants received placebo subcutaneous injection once a week for 26 weeks. Receives: Drug: Placebo |
| Mipomersen | Experimental | Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks. 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) 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.
Measured: 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.
Measured: 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
Apolipoprotein B was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Measured: 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
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Measured: 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
Total cholesterol was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Measured: 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
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Measured: 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
Non-high-density lipoprotein cholesterol was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Measured: 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).
Non-High-Density Lipoprotein 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.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2008 (estimated)
- Study startNov 2008
- Primary completionMay 2010
- Study completionOct 2010
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 HypercholesterolemiaStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 158 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kastle Therapeutics, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ionis Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Genzyme, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00770146
- Sponsor's protocol ID
- 301012-CS12
- Status last verified
- Aug 2016
- First submitted
- 8 Oct 2008
- Last updated
- 9 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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 25614280Thomas 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.
PubMed 24013058
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
- A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) as Add-on Therapy in High Risk Hypercholesterolemic Patients
- ClinicalTrials.gov ID
- NCT00770146
- Acronym / sponsor ID
- 301012-CS12
- Conditions
- Hypercholesterolemia, Coronary Heart Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 158 participants (actual)
- Lead sponsor
- Kastle Therapeutics, LLCIndustry (pharma, biotech, devices)
- Collaborators
- Ionis Pharmaceuticals, Inc.
- Study start
- Nov 2008
- Primary completion
- May 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 9 Oct 2008 (estimated)
- Results
- Posted 20 Mar 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Hypercholesterolemia is characterized by markedly elevated low density lipoproteins (LDL). Elevated LDL is a major risk factor for 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 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 patients with high cholesterol who are at high risk for CHD and who are already on the maximally tolerated dose of statin.
This study consisted of a 26-week treatment period and a 24-week post-treatment follow-up period. Participants who finished treatment or who discontinued prematurely from the study for any reason were assessed for safety for 24 weeks after the last study drug dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboParticipants received placebo subcutaneous injection once a week for 26 weeks. |
| Mipomersen | Experimental | Drug: Mipomersen sodiumParticipants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (1 listed)
- 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.
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™200 mg/mL | Drug | Mipomersen |
| Placebo1 mL matching placebo (i.e., vehicle consisting of 9 mg of sodium chloride, 0.004 mg of riboflavin, filled to 1 mL with water). | Drug | Placebo |
Primary outcome
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the 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; Week 28 or the post-baseline visit closest to 14 days after the last dose).
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.
Low-density Lipoprotein Cholesterol (LDL-C) at Baseline and at the 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; Week 28 or the post-baseline visit closest to 14 days after the last dose).
The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
6 secondary outcomes
Percent Change From Baseline in Apolipoprotein B at the 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; 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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).
Non-High-Density Lipoprotein Cholesterol at Baseline and at the 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; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Results and safety
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 25614280Santos 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.
- Derived from this study: PubMed 24013058Thomas 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.
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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
62 sites in 1 country: 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 Hypercholesterolemia and Coronary Heart Disease, run by Kastle Therapeutics, LLC at 62 sites in United States.
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 5 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 62 sites in United States. 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 20 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 the 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; Week 28 or the post-baseline visit closest to 14 days after the last dose).). 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 NCT00770146, 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.