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

November 17, 2011
April 8, 2014
December 2011
February 2015   (final data collection date for primary outcome measure)
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 ]
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 ]
Complete list of historical versions of study NCT01475825 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 ]
Not Provided
Not Provided
 
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, 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.

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

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Hypercholesterolemia
  • Heterozygous Familial
  • Drug: mipomersen sodium 200 mg
    200 mg (200 mg/mL in a volume of 1 mL), subcutaneous injections
    Other Name: Kynamro (ISIS 301012)
  • Drug: Placebo
    Placebo vehicle for subcutaneous injection.
  • Drug: mipomersen sodium 70 mg
    70 mg (140 mg/mL in a volume of 0.5 mL), subcutaneous injections
    Other Name: Kynamro (ISIS 301012)
  • 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.
    Intervention: Drug: mipomersen sodium 200 mg
  • 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.
    Intervention: Drug: Placebo
  • 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.
    Intervention: Drug: mipomersen sodium 70 mg
  • 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.
    Intervention: Drug: Placebo
  • 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
    Intervention: Drug: mipomersen sodium 200 mg
  • 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.
    Intervention: Drug: mipomersen sodium 70 mg
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
300
February 2016
February 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Belgium,   Brazil,   Canada,   Croatia,   Czech Republic,   Denmark,   Germany,   Greece,   Hong Kong,   Hungary,   India,   Israel,   Italy,   Korea, Republic of,   Malaysia,   Netherlands,   New Zealand,   Norway,   Poland,   Russian Federation,   South Africa,   Spain,   Sweden,   Taiwan,   Turkey,   Ukraine,   United Kingdom
 
NCT01475825
MIPO3801011, 2011-001480-42, EFC12875
Yes
Sanofi ( Genzyme, a Sanofi Company )
Genzyme, a Sanofi Company
Not Provided
Study Director: Medical Monitor Genzyme, a Sanofi Company
Sanofi
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP