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 - Full Text View

Purpose

The primary objective of this study is to 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 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.

Condition	Intervention	Phase
Hypercholesterolemia Coronary Heart Disease	Drug: mipomersen sodium 200 mg Drug: Placebo Drug: mipomersen sodium 70 mg	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess the Safety and Efficacy or Two Different Regimens of Mipomersen in Patients With Severe Familial Hypercholesterolemia

Resource links provided by NLM:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease Farber lipogranulomatosis hypercholesterolemia

MedlinePlus related topics: Cholesterol Coronary Artery Disease Heart Diseases

Drug Information available for: Mipomersen sodium Mipomersen

U.S. FDA Resources

Further study details as provided by Genzyme:

Primary Outcome Measures:

Percent change from Baseline in low-density lipoprotein cholesterol (LDL-C) in Cohort 1 [ Time Frame: Baseline and Week 60 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Percent Change from Baseline in Apolipoprotein B (Apo B) [ Time Frame: Baseline and Week 60 ] [ Designated as safety issue: No ]
Percent Change from Baseline in Lipoprotein a [ Time Frame: Baseline and Week 60 ] [ Designated as safety issue: No ]
Percent Change from Baseline in LDL-C in Cohort 2 [ Time Frame: Baseline and Week 60 ] [ Designated as safety issue: No ]
Number of Participants with Adverse Events [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]
Number of Participants with Injection Site Reactions [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]
Blood plasma concentration of Mipomersen [ Time Frame: Pre-dose and at 2, 4, 6, 24, 48 and 72 hours post-dose at Weeks 1, 30, 36 and 60. ] [ Designated as safety issue: No ]

Estimated Enrollment:	480
Study Start Date:	December 2011
Estimated Study Completion Date:	May 2015
Estimated Primary Completion Date:	November 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Mipomersen 200mg once weekly Mipomersen sodium 200 mg (1 mL), subcutaneous injections administered once every other week for the first 8 weeks followed by once every week for 52 weeks.	Drug: mipomersen sodium 200 mg 200 mg (200 mg/mL in a volume of 1 mL), subcutaneous injections administered once every other week for the first 8 weeks followed by once every week for 52 weeks. Other Name: ISIS301012
Placebo Comparator: Placebo once weekly Placebo subcutaneous injection (1 mL) administered once every other week for the first 8 weeks followed by once a week for 52 weeks.	Drug: Placebo Placebo vehicle for subcutaneous injection.
Experimental: Mipomersen 70mg thrice weekly Mipomersen sodium 70 mg (0.5 mL), subcutaneous injections administered three times a week every other week for the first 8 weeks followed by three times a week every week for 52 weeks.	Drug: mipomersen sodium 70 mg 70 mg (140 mg/mL in a volume of 0.5 mL), administered by subcutaneous injection three times a week every other week for the first 8 weeks followed by three injections per week every week for 52 weeks. Other Name: ISIS301012
Placebo Comparator: Placebo thrice weekly Placebo subcutaneous injection (0.5 mL) three times a week every other week for the first 8 weeks followed by three times every week for 52 weeks.	Drug: Placebo Placebo vehicle for subcutaneous injection.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01475825

Contacts

Contact: Medical Information	800-745-4447	medinfo@genzyme.com
Contact: Medical Information	617-252-7832	medinfo@genzyme.com

Show 121 Study Locations

Sponsors and Collaborators

Genzyme

Investigators

Study Director:

Medical Monitor

Genzyme

More Information

No publications provided

Responsible Party:	Genzyme
ClinicalTrials.gov Identifier:	NCT01475825 History of Changes
Other Study ID Numbers:	MIPO3801011, 2011-001480-42
Study First Received:	November 17, 2011
Last Updated:	May 7, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Hypercholesterolemia
Hyperlipoproteinemia Type II
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases

Vascular Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias

ClinicalTrials.gov processed this record on May 16, 2013

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)