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)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT01475825
First received: November 17, 2011
Last updated: April 8, 2014
Last verified: April 2014
  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:


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
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: April 8, 2014
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
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias

ClinicalTrials.gov processed this record on April 22, 2014