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 Grandville Michigan

Grandville, Michigan

from

Grandville, MI