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

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	Intervention	Phase
Hypercholesterolemia Heterozygous Familial	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:	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

Resource links provided by NLM:

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

MedlinePlus related topics: Cholesterol

Drug Information available for: Mipomersen sodium Mipomersen

Genetic and Rare Diseases Information Center resources: Hyperlipoproteinemia Type 2 Sphingolipidosis

U.S. FDA Resources

Further study details as provided by Sanofi:

Primary Outcome Measures:

Percent change from Baseline in low-density lipoprotein cholesterol (LDL-C) in Cohort 1 [ Time Frame: Baseline to primary endpoint visit (PET) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Percent Change from Baseline in Apolipoprotein B (Apo B) [ Time Frame: Baseline to PET ] [ Designated as safety issue: No ]
Percent Change from Baseline in Lipoprotein a [ Time Frame: Baseline to PET ] [ Designated as safety issue: No ]
Percent Change from Baseline in LDL-C in Cohort 2 [ Time Frame: Baseline to PET ] [ Designated as safety issue: No ]


Estimated Enrollment:	300
Study Start Date:	December 2011
Estimated Study Completion Date:	February 2016
Estimated Primary Completion Date:	February 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Blinded mipomersen 200 mg 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 Other Name: Kynamro (ISIS 301012)
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: Blinded mipomersen 70 mg 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), subcutaneous injections Other Name: Kynamro (ISIS 301012)
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.
Experimental: Open-label mipomersen 200 mg once weekly Mipomersen sodium 200 mg (1 mL), subcutaneous injections administered once every week for 26 weeks following completion of blinded treatment period	Drug: mipomersen sodium 200 mg 200 mg (200 mg/mL in a volume of 1 mL), subcutaneous injections Other Name: Kynamro (ISIS 301012)
Experimental: Open-label mipomersen 70 mg thrice weekly Mipomersen sodium 70 mg (0.5 mL), subcutaneous injections administered three times a week for 26 weeks following completion of blinded treatment period.	Drug: mipomersen sodium 70 mg 70 mg (140 mg/mL in a volume of 0.5 mL), subcutaneous injections Other Name: Kynamro (ISIS 301012)

Detailed Description:

The study consists 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 is blinded (double-blinded) through the Primary Efficacy Assessment Visit in the Blinded Treatment Period. Study treatment is open-label in the Open-Label Continuation Period.

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Show 131 Study Locations

Sponsors and Collaborators

Genzyme, a Sanofi Company

Investigators


Study Director:	Medical Monitor	Genzyme, a Sanofi Company

More Information

No publications provided


Responsible Party:	Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:	NCT01475825 History of Changes
Other Study ID Numbers:	MIPO3801011, 2011-001480-42, EFC12875
Study First Received:	November 17, 2011
Last Updated:	January 27, 2015
Health Authority:	United States: Food and Drug Administration Canada: Health Canada Belgium: Federal Agency for Medicines and Health Products, FAMHP New Zealand: Medsafe Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines Germany: Federal Institute for Drugs and Medical Devices South Africa: Medicines Control Council Netherlands: Ministry of Health, Welfare and Sport Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Malaysia: Ministry of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency Sweden: Medical Products Agency Czech Republic: State Institute for Drug Control Israel: Israeli Health Ministry Pharmaceutical Administration Australia: Department of Health and Ageing Therapeutic Goods Administration Greece: Ministry of Health and Social Solidarity National Organization for Medicines Spain: Spanish Agency for Medications and Health Products Russia: Ministry of Public Health and Social Development of the Russian Federation Hong Kong: Department of Health Italy: The Italian Medicines Agency Ukraine: Ministry of Health Taiwan : Food and Drug Administration Norway: Norwegian Medicines Agency Croatia: Ministry of Health and Social Care India: Drugs Controller General of India Argentina: National Administration of Drugs, Foods and Medical Devices, ANMAT Brazil: National Health Surveillance Agency Turkey: Ministry of Health South Korea: Korea Food and Drug Administration (KFDA) Denmark: Danish Health and Medicines Authority

Additional relevant MeSH terms:


Hypercholesterolemia Hyperlipoproteinemia Type II Dyslipidemias Genetic Diseases, Inborn Hyperlipidemias Hyperlipoproteinemias Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Metabolic Diseases Metabolism, Inborn Errors	Mipomersen Anticholesteremic Agents Antimetabolites Diagnostic Uses of Chemicals Hypolipidemic Agents Lipid Regulating Agents Molecular Mechanisms of Pharmacological Action Molecular Probes Pharmacologic Actions Therapeutic Uses

ClinicalTrials.gov processed this record on February 27, 2015

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)