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

Status:	Completed
Conditions:	High Cholesterol, Peripheral Vascular Disease, Cardiology
Therapuetic Areas:	Cardiology / Vascular Diseases
Healthy:	No
Age Range:	18 - Any
Updated:	3/28/2019
Start Date:	December 2011
End Date:	December 29, 2015

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 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.

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

We found this trial at

sites

Clinical Trial Facility in Ciudad Autonoma de Buenos Aires

Ciudad Autonoma de Buenos Aires,

5602

from

Ciudad Autonoma de Buenos Aires,