NCT01475825

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

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 309 (actual)
• Sponsor: Kastle Therapeutics, LLC · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Hypercholesterolemia
• Heterozygous Familial

Interventions

Type	Name	Description
DRUG	mipomersen sodium 200 mg	Subcutaneous mipomersen 200 mg once weekly
DRUG	Placebo	Placebo vehicle for subcutaneous injection.
DRUG	mipomersen sodium 70 mg	Subcutaneous mipomersen 70 mg thrice weekly

Timeline

• Start date: 2011-12-01
• Primary completion: 2015-12-29
• Completion: 2015-12-29
• First posted: 2011-11-21
• Last updated: 2019-03-26
• Results posted: 2019-03-14

Locations

113 sites across 30 countries: United States, Argentina, Australia, Belgium, Brazil, Canada, Croatia, Czechia, Denmark, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Malaysia, Netherlands, New Zealand, Norway, Poland, Russia, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom