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)

Kastle Therapeutics

Status and phase: Completed; Phase 3

Conditions: Hypercholesterolemia; Heterozygous Familial

Treatments: Drug: Placebo; Drug: mipomersen sodium 70 mg; Drug: mipomersen sodium 200 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01475825

2011-001480-42 (EudraCT Number)

EFC12875 (Other Identifier)

MIPO3801011

Details and patient eligibility

About

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

Full 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.

Enrollment: 309 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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309 participants in 4 patient groups, including a placebo group

Regimen A: Mipomersen

Experimental group

Description:

Subcutaneous injection of mipomersen 200 mg once weekly

Treatment:

Drug: mipomersen sodium 200 mg

Regimen A: Placebo

Placebo Comparator group

Description:

Placebo matching subcutaneous injection once weekly.

Treatment:

Drug: Placebo

Regimen B: Mipomersen

Experimental group

Description:

Subcutaneous injection of mipomersen 70 mg thrice weekly.

Treatment:

Drug: mipomersen sodium 70 mg

Regimen B: Placebo

Placebo Comparator group

Description:

Placebo matching subcutaneous injection thrice weekly.

Treatment:

Drug: Placebo