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 (FOCUS FH)
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| ClinicalTrials.gov Identifier: NCT01475825 |
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Recruitment Status :
Completed
First Posted : November 21, 2011
Results First Posted : March 14, 2019
Last Update Posted : March 26, 2019
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Sponsor:
Kastle Therapeutics, LLC
Information provided by (Responsible Party):
Kastle Therapeutics, LLC
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Brief 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 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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hypercholesterolemia Heterozygous Familial | Drug: mipomersen sodium 200 mg Drug: Placebo Drug: mipomersen sodium 70 mg | Phase 3 |
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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 309 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | December 2011 |
| Actual Primary Completion Date : | December 29, 2015 |
| Actual Study Completion Date : | December 29, 2015 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Familial hypercholesterolemia
| Arm | Intervention/treatment |
|---|---|
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Experimental: Regimen A: Mipomersen
Subcutaneous injection of mipomersen 200 mg once weekly
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Drug: mipomersen sodium 200 mg
Subcutaneous mipomersen 200 mg once weekly
Other Name: Kynamro (ISIS 301012) |
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Placebo Comparator: Regimen A: Placebo
Placebo matching subcutaneous injection once weekly.
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Drug: Placebo
Placebo vehicle for subcutaneous injection. |
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Experimental: Regimen B: Mipomersen
Subcutaneous injection of mipomersen 70 mg thrice weekly.
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Drug: mipomersen sodium 70 mg
Subcutaneous mipomersen 70 mg thrice weekly
Other Name: Kynamro (ISIS 301012) |
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Placebo Comparator: Regimen B: Placebo
Placebo matching subcutaneous injection thrice weekly.
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Drug: Placebo
Placebo vehicle for subcutaneous injection. |
Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- Percent Change From Baseline To PET In LDL-C In Cohort 2 [ Time Frame: Baseline, PET (up to 60 weeks) ]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.
- Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 1 [ Time Frame: Baseline and Week 61 ]The percent change from baseline to PET in Apo B was measured in participants in Cohort 1 with HeFH during the Blinded Treatment Period.
- Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 2 [ Time Frame: Baseline and Week 61 ]The percent change from baseline to PET in Apo B was measured in participants in Cohort 2 with HeFH during the Blinded Treatment Period.
- Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 1 [ Time Frame: Baseline and Week 61 ]The percent change from baseline to PET in Lipoprotein A1 was measured in participants in Cohort 1 with HeFH during the Blinded Treatment Period.
- Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 2 [ Time Frame: Baseline and Week 61 ]The percent change from baseline to PET in Lipoprotein A1 was measured in participants in Cohort 2 with HeFH during the Blinded Treatment Period.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01475825
Locations
Show 116 study locations
Sponsors and Collaborators
Kastle Therapeutics, LLC
Investigators
| Study Director: | Medical Monitor | Genzyme, a Sanofi Company |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Kastle Therapeutics, LLC |
| ClinicalTrials.gov Identifier: | NCT01475825 |
| Other Study ID Numbers: |
MIPO3801011 2011-001480-42 ( EudraCT Number ) EFC12875 ( Other Identifier: Sanofi ) |
| First Posted: | November 21, 2011 Key Record Dates |
| Results First Posted: | March 14, 2019 |
| Last Update Posted: | March 26, 2019 |
| Last Verified: | March 2019 |
Additional relevant MeSH terms:
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Hyperlipoproteinemia Type II Hypercholesterolemia Hyperlipidemias Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases Lipid Metabolism, Inborn Errors Metabolism, Inborn Errors |
Genetic Diseases, Inborn Hyperlipoproteinemias Mipomersen Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents |