HypercholesterolemiaPhase 3FOCUS FHNCT01475825
A Study of the Safety and Efficacy of Two Different Regimens of Mipomersen in Patients With Familial Hypercholesterolemia and Inadequately Controlled Low-Density Lipoprotein Cholesterol
A Phase 3 study testing mipomersen sodium 200 mg and mipomersen sodium 70 mg in people with Hypercholesterolemia and Heterozygous Familial, run by Kastle Therapeutics, LLC at 113 sites in 30 countries.
Trial summary
Primary objective: Determine whether mipomersen (ISIS 301012) significantly reduces atherogenic lipid levels in patients with severe heterozygous familial hypercholesterolemia (severe HeFH), defined as low-density lipoprotein cholesterol (LDL-C) levels ≥200 mg/dL plus the presence of coronary heart disease (CHD)/risk… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypercholesterolemia, Heterozygous Familial
- What is being tested?
- mipomersen sodium 200 mg and mipomersen sodium 70 mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 309 participants
- Where
- 113 sitesin 30 countries
- Study dates
- Dec 2011to 29 Dec 2015
- 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 severe hypercholesterolemia (LDL-C ≥300 mg/dL (7.77 mmol/L) or LDL-C ≥200 mg/dL (5.18 mmol/L) with documented coronary heart disease (CHD) or CHD risk equivalents, or diagnosis of Heterozygous Familial Hypercholesterolemia and LDL-C ≥160 mg/dL (4.14 mmol/L) and <200 mg/dL (5.18 mmol/L))
- On stable, maximally tolerated, statin therapy for at least 12 weeks or if statin intolerant, on at least 1 medication from another class of hypolipidemic agents (i.e., bile acid sequestrants, niacin/nicotinic acid, cholesterol absorption inhibitors, fibrates).
- On stable, low fat diet for 12 weeks
- Body mass index (BMI) ≤40 kg/m2 and 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
113 sites in 30 countries.
113 sites in 30 countries
United States20 sites
Study site
Ann Arbor, Michigan
Study site
Aurora, Colorado
Study site
Boston, Massachusetts
Study site
Charleston, South Carolina
Study site
Cooper City, Florida
Study site
Dallas, Texas
Study site
Grandville, Michigan
Study site
Indianapolis, Indiana
Study site
Kansas City, Kansas
Study site
Lancaster, Pennsylvania
Study site
Mission Viejo, California
Study site
Nashville, Tennessee
Study site
Norfolk, Virginia
Study site
North Massapequa, New York
Study site
Omaha, Nebraska
Study site
Portland, Oregon
Study site
Rochester, Minnesota
Study site
St Louis, Missouri
Study site
Summit, New Jersey
Study site
Winter Park, Florida
Poland10 sites
Study site
Bialystok
Study site
Gdansk
Study site
Katowice
Study site
Krakow
Study site
Nałęczów
Study site
Poznan
Study site
Sopot
Study site
Szczecin
Study site
Warsaw
Study site
Wroclaw
Russia9 sites
Study site
Barnaul
Study site
Kemerovo
Study site
Moscow
Study site
Novosibirsk
Study site
Petrozavodsk
Study site
Ryazan
Study site
Saint Petersburg
Study site
Tomsk
Study site
Yaroslavl
Germany7 sites
Study site
Aachen
Study site
Berlin
Study site
Cologne
Study site
Freiburg im Breisgau
Study site
Hamburg
Study site
Heidelberg
Study site
Magdeburg
Italy6 sites
Study site
Bologna
Study site
Naples
Study site
Padova
Study site
Palermo
Study site
Pisa
Study site
Roma
Netherlands6 sites
Study site
Alkmaar
Study site
Amsterdam
Study site
Maastricht
Study site
Nijmegen
Study site
Utrecht
Study site
Waalwijk
United Kingdom6 sites
Study site
Birmingham
Study site
Cardiff
Study site
Liverpool
Study site
London
Study site
Manchester
Study site
Oldham
Turkey (Türkiye)4 sites
Study site
Ankara
Study site
Istanbul
Study site
Izmir
Study site
Sivas
Ukraine4 sites
Study site
Ivano-Frankivsk
Study site
Kiev
Study site
Kyiv
Study site
Odesa
Canada3 sites
Study site
Chicoutimi, Quebec
Study site
Montreal, Quebec
Study site
Sainte-Foy, Quebec
About this study
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Followed by an Open-Label Continuation Period to Assess the Safety and Efficacy of Two Different Regimens of Mipomersen in Patients With Familial Hypercholesterolemia and Inadequately Controlled Low-Density Lipoprotein Cholesterol
Primary objective:
Determine whether mipomersen (ISIS 301012) significantly reduces atherogenic lipid levels in patients with severe heterozygous familial hypercholesterolemia (severe HeFH), defined as low-density lipoprotein cholesterol (LDL-C) levels ≥200 mg/dL plus the presence of coronary heart disease (CHD)/risk equivalents or LDL-C levels ≥300 mg/dL regardless of the presence of CHD/risk equivalents (referred to as Cohort 1) compared to placebo. Two different mipomersen dosing regimens will be studied: subcutaneous (SC) mipomersen 200 mg once weekly versus placebo, and SC mipomersen 70 mg thrice weekly versus placebo.
Read more
Secondary Objectives:
- Determine whether there are qualitative differences between the safety profiles of the 2 dosing regimens and placebo in Cohort 1, patients with HeFH with LDL-C levels ≥160 mg/dL and <200 mg/dL plus the presence of CHD/risk equivalents (referred to as Cohort 2), and the overall study population
- Determine whether there are qualitative differences between the tolerability of the 2 dosing regimens and placebo in Cohort 1, Cohort 2, and the overall study population
- Further characterize the pharmacokinetics (PK) of the 2 dosing regimens in Cohort 1, Cohort 2, and the overall study population
- Determine whether the 2 mipomersen dosing regimens significantly reduce atherogenic lipid levels in Cohort 2 compared to placebo
- Obtain additional data regarding ongoing safety and efficacy of mipomersen in patients with FH and inadequately controlled LDL-C who complete the primary efficacy assessment visit (PET) in the Blinded Treatment Period and continue treatment in Open-Label Continuation Period
Read the detailed description
The study consisted of a Screening period of up to 4 weeks, Blinded Treatment Phase of 60 weeks, Open-Label Continuation Period of 26 weeks, and Post-Treatment Phase of 24 weeks.
Study Design, masking - Study treatment was blinded (double-blinded) through the Primary Efficacy Assessment Visit in the Blinded Treatment Period. Study treatment was open-label in the Open-Label Continuation Period.
- Conditions
- Hypercholesterolemia, Heterozygous Familial
- Being tested
- mipomersen sodium 200 mg, Placebo, mipomersen sodium 70 mg
- Medical subject headings
- Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mipomersen sodium 200 mgDrug
Also called Kynamro (ISIS 301012)
Subcutaneous mipomersen 200 mg once weekly
PlaceboDrug
Placebo vehicle for subcutaneous injection.
mipomersen sodium 70 mgDrug
Also called Kynamro (ISIS 301012)
Subcutaneous mipomersen 70 mg thrice weekly
| Study group | Role | What they receive |
|---|---|---|
| Regimen A: Mipomersen | Experimental | Subcutaneous injection of mipomersen 200 mg once weekly Receives: Drug: mipomersen sodium 200 mg |
| Regimen A: Placebo | Placebo comparator | Placebo matching subcutaneous injection once weekly. Receives: Drug: Placebo |
| Regimen B: Mipomersen | Experimental | Subcutaneous injection of mipomersen 70 mg thrice weekly. Receives: Drug: mipomersen sodium 70 mg |
| Regimen B: Placebo | Placebo comparator | Placebo matching subcutaneous injection thrice weekly. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline To Primary Endpoint Visit (PET) In LDL-C In Cohort 1
The percent change from baseline to PET in LDL-C was measured in Cohort 1, which included participants with severe heterozygous familial hypercholesterolemia (HeFH). Severe HeFH was defined as LDL-C levels ≥200 mg/deciliter (dL) plus the presence of coronary heart disease (CHD)/risk equivalents or LDL-C levels ≥300 mg/dL regardless of the presence of CHD/risk equivalents.
Measured: Baseline and Week 61
Secondary outcomes (5)
Percent Change From Baseline To PET In LDL-C In Cohort 2
The percent change from baseline to PET in LDL-C was measured in Cohort 2, which included participants with HeFH with LDL-C levels ≥160 mg/dL and <200 mg/dL, plus the presence of CHD/risk equivalents.
Measured: Baseline, PET (up to 60 weeks)
Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 1
The percent change from baseline to PET in Apo B was measured in participants in Cohort 1 with HeFH during the Blinded Treatment Period.
Measured: Baseline and Week 61
Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 2
The percent change from baseline to PET in Apo B was measured in participants in Cohort 2 with HeFH during the Blinded Treatment Period.
Measured: Baseline and Week 61
Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 1
The percent change from baseline to PET in Lipoprotein A1 was measured in participants in Cohort 1 with HeFH during the Blinded Treatment Period.
Measured: Baseline and Week 61
Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 2
The percent change from baseline to PET in Lipoprotein A1 was measured in participants in Cohort 2 with HeFH during the Blinded Treatment Period.
Measured: Baseline and Week 61
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2011 (estimated)
- Study startDec 2011
- Primary completion29 Dec 2015
- Study completion29 Dec 2015
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 (1)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
- 309 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kastle Therapeutics, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Genzyme, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01475825
- Sponsor's protocol ID
- MIPO3801011
- Other IDs
- 2011-001480-42, EFC12875
- Acronym
- FOCUS FH
- Status last verified
- Mar 2019
- First submitted
- 17 Nov 2011
- Last updated
- 26 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Tragante V, Asselbergs FW, Swerdlow DI, Palmer TM, Moore JH, de Bakker PIW, Keating BJ, Holmes MV. Harnessing publicly available genetic data to prioritize lipid modifying therapeutic targets for prevention of coronary heart disease based on dysglycemic risk. Hum Genet. 2016 May;135(5):453-467. doi: 10.1007/s00439-016-1647-9. Epub 2016 Mar 5.
PubMed 26946290
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Followed by an Open-Label Continuation Period to Assess the Safety and Efficacy of Two Different Regimens of Mipomersen in Patients With Familial Hypercholesterolemia and Inadequately Controlled Low-Density Lipoprotein Cholesterol
- ClinicalTrials.gov ID
- NCT01475825
- Acronym / sponsor ID
- FOCUS FH / MIPO3801011
- Conditions
- Hypercholesterolemia, Heterozygous Familial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 309 participants (actual)
- Lead sponsor
- Kastle Therapeutics, LLCIndustry (pharma, biotech, devices)
- Study start
- Dec 2011 (actual)
- Primary completion
- 29 Dec 2015 (actual)
- Study completion
- 29 Dec 2015 (actual)
- First posted
- 21 Nov 2011 (estimated)
- Results
- Posted 14 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary objective:
Determine whether mipomersen (ISIS 301012) significantly reduces atherogenic lipid levels in patients with severe heterozygous familial hypercholesterolemia (severe HeFH), defined as low-density lipoprotein cholesterol (LDL-C) levels ≥200 mg/dL plus the presence of coronary heart disease (CHD)/risk equivalents or LDL-C levels ≥300 mg/dL regardless of the presence of CHD/risk equivalents (referred to as Cohort 1) compared to placebo. Two different mipomersen dosing regimens will be studied: subcutaneous (SC) mipomersen 200 mg once weekly versus placebo, and SC mipomersen 70 mg thrice weekly versus placebo.
Secondary Objectives:
- Determine whether there are qualitative differences between the safety profiles of the 2 dosing regimens and placebo in Cohort 1, patients with HeFH with LDL-C levels ≥160 mg/dL and <200 mg/dL plus the presence of CHD/risk equivalents (referred to as Cohort 2), and the overall study population
- Determine whether there are qualitative differences between the tolerability of the 2 dosing regimens and placebo in Cohort 1, Cohort 2, and the overall study population
- Further characterize the pharmacokinetics (PK) of the 2 dosing regimens in Cohort 1, Cohort 2, and the overall study population
- Determine whether the 2 mipomersen dosing regimens significantly reduce atherogenic lipid levels in Cohort 2 compared to placebo
- Obtain additional data regarding ongoing safety and efficacy of mipomersen in patients with FH and inadequately controlled LDL-C who complete the primary efficacy assessment visit (PET) in the Blinded Treatment Period and continue treatment in Open-Label Continuation Period
Detailed description
The study consisted of a Screening period of up to 4 weeks, Blinded Treatment Phase of 60 weeks, Open-Label Continuation Period of 26 weeks, and Post-Treatment Phase of 24 weeks.
Study Design, masking - Study treatment was blinded (double-blinded) through the Primary Efficacy Assessment Visit in the Blinded Treatment Period. Study treatment was open-label in the Open-Label Continuation Period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Regimen A: Mipomersen | Experimental | Drug: mipomersen sodium 200 mgSubcutaneous injection of mipomersen 200 mg once weekly |
| Regimen A: Placebo | Placebo comparator | Drug: PlaceboPlacebo matching subcutaneous injection once weekly. |
| Regimen B: Mipomersen | Experimental | Drug: mipomersen sodium 70 mgSubcutaneous injection of mipomersen 70 mg thrice weekly. |
| Regimen B: Placebo | Placebo comparator | Drug: PlaceboPlacebo matching subcutaneous injection thrice weekly. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of severe hypercholesterolemia (LDL-C ≥300 mg/dL (7.77 mmol/L) or LDL-C ≥200 mg/dL (5.18 mmol/L) with documented coronary heart disease (CHD) or CHD risk equivalents, or diagnosis of Heterozygous Familial Hypercholesterolemia and LDL-C ≥160 mg/dL (4.14 mmol/L) and <200 mg/dL (5.18 mmol/L))
- On stable, maximally tolerated, statin therapy for at least 12 weeks or if statin intolerant, on at least 1 medication from another class of hypolipidemic agents (i.e., bile acid sequestrants, niacin/nicotinic acid, cholesterol absorption inhibitors, fibrates).
- On stable, low fat diet for 12 weeks
- Body mass index (BMI) ≤40 kg/m2 and stable weight for > 6 weeks
Key exclusion criteria (2 listed)
- 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
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 sodium 200 mgAlso: Kynamro (ISIS 301012)Subcutaneous mipomersen 200 mg once weekly | Drug | Regimen A: Mipomersen |
| PlaceboPlacebo vehicle for subcutaneous injection. | Drug | Regimen A: Placebo, Regimen B: Placebo |
| mipomersen sodium 70 mgAlso: Kynamro (ISIS 301012)Subcutaneous mipomersen 70 mg thrice weekly | Drug | Regimen B: Mipomersen |
Primary outcome
Percent Change From Baseline To Primary Endpoint Visit (PET) In LDL-C In Cohort 1
Time frame: Baseline and Week 61
The percent change from baseline to PET in LDL-C was measured in Cohort 1, which included participants with severe heterozygous familial hypercholesterolemia (HeFH). Severe HeFH was defined as LDL-C levels ≥200 mg/deciliter (dL) plus the presence of coronary heart disease (CHD)/risk equivalents or LDL-C levels ≥300 mg/dL regardless of the presence of CHD/risk equivalents.
5 secondary outcomes
Percent Change From Baseline To PET In LDL-C In Cohort 2
Time frame: Baseline, PET (up to 60 weeks)
Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 1
Time frame: Baseline and Week 61
Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 2
Time frame: Baseline and Week 61
Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 1
Time frame: Baseline and Week 61
Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 2
Time frame: Baseline and Week 61
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26946290Tragante V, Asselbergs FW, Swerdlow DI, Palmer TM, Moore JH, de Bakker PIW, Keating BJ, Holmes MV. Harnessing publicly available genetic data to prioritize lipid modifying therapeutic targets for prevention of coronary heart disease based on dysglycemic risk. Hum Genet. 2016 May;135(5):453-467. doi: 10.1007/s00439-016-1647-9. Epub 2016 Mar 5.
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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
113 sites in 30 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing mipomersen sodium 200 mg and mipomersen sodium 70 mg in people with Hypercholesterolemia and Heterozygous Familial, run by Kastle Therapeutics, LLC at 113 sites in 30 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 4 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 26 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 113 sites in United States, Poland, Russia, Germany, Italy and 25 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. 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 14 Mar 2019). 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 To Primary Endpoint Visit (PET) In LDL-C In Cohort 1 (time frame: Baseline and Week 61). 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 NCT01475825, which also lists 1 linked publication.
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 26 Mar 2019.