Conditions: Hypercholesterolemia Heterozygous Familial
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 309
Healthy volunteers: no

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

Detailed description:
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.

Arms:
arm 1: Subcutaneous injection of mipomersen 200 mg once weekly arm 2: Placebo matching subcutaneous injection once weekly. arm 3: Subcutaneous injection of mipomersen 70 mg thrice weekly. arm 4: Placebo matching subcutaneous injection thrice weekly.

Interventions: intervention 1: mipomersen sodium 200 mg intervention 2: Placebo intervention 3: mipomersen sodium 70 mg
Intervention descriptions: intervention 1: Subcutaneous mipomersen 200 mg once weekly intervention 2: Placebo vehicle for subcutaneous injection. intervention 3: Subcutaneous mipomersen 70 mg thrice weekly

Protocol document: