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

• Register: EUCTR
• Last refreshed on: 9 May 2016
• Main ID: EUCTR2011-001480-42-ES
• Date of registration: 23/11/2011
• Prospective Registration: Yes
• Primary sponsor: Genzyme Corporation and its Affiliates
• Public title: 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
• Scientific title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Safety and Efficacy of Two Different Regimens of Mipomersen in Patients with Familial Hypercholesterolemia and Inadequately Controlled Low-Density-Lipoprotein Cholesterol - FOCUS FH
• Date of first enrolment: 26/04/2012
• Target sample size: 900
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-001480-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, Croatia, Czech Republic, Denmark, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Malaysia, Netherlands, New Zealand, Norway, Poland, Russian Federation, Slovakia, South Africa, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Medical Information Genzyme Europe
• Affiliation: Genzyme Europe B.V.

• Name: Medical Information Genzyme Europe
• Affiliation: Genzyme Europe B.V.

Key inclusion & exclusion criteria

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) and documented coronary heart disease (CHD) or CHD risk equivalent 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 460
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Heterozygous familial hypercholesterolemia
MedDRA version: 14.1 Level: LLT Classification code 10057079 Term: Heterozygous familial hypercholesterolemia System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: Mipomersen
Product Code: ISIS 301012
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Mipomersen
CAS Number: 629167-92-6
Current Sponsor code: ISIS 301012
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Product Name: Mipomersen
Product Code: ISIS 301012
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Mipomersen
CAS Number: 629167-92-6
Current Sponsor code: ISIS 301012
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 140-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Baseline to Week 60

Primary end point(s): Percent change from Baseline in low-density lipoprotein cholesterol in Cohort 1

Main 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 Objective: - 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 (comprising patients in both Cohort 1 and Cohort 2)
- 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

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Percent change from Baseline in Apolipoprotein : Baseline to Week 60
Percent change from Baseline in Lipoprotein a : Baseline to Week 60
Percent change from Baseline in low-density lipoprotein cholesterol in Cohort 2 : Baseline to Week 60
Number of Participants with Adverse Events : 60 weeks
Number of Participants with injection site reactions : 60 weeks
Blood plasma concentration of Mipomersen : Pre-dose and at 2, 4, 6, 24, 48 and 72 hours post-dose at Weeks 1, 30, 36 and 60.

Secondary end point(s): Percent change from Baseline in Apolipoprotein
Percent change from Baseline in Lipoprotein a
Percent change from Baseline in low-density lipoprotein cholesterol in Cohort 2
Number of Participants with Adverse Events
Number of Participants with injection site reactions
Blood plasma concentration of Mipomersen

Secondary ID(s)

MIPO3801011

Source(s) of Monetary Support

Genzyme Corporation and its Affiliates