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: 11 April 2016
• Main ID: EUCTR2011-001480-42-BE
• Date of registration: 07/12/2011
• 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 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 - FOCUS FH
• Date of first enrolment: 30/01/2012
• Target sample size: 300
• 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: yes Other trial design description: Optional continuation period: open label study and all patients will receive mipomersen If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 6

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, Croatia, Czech Republic, Denmark, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Korea, Republic of, 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 240
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

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

Heterozygous familial hypercholesterolemia
MedDRA version: 16.1 Level: LLT Classification code 10057079 Term: Heterozygous familial hypercholesterolemia System Organ Class: 100000004850

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

Intervention(s)

Trade Name: Kynamro
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
Other descriptive name: GZ402661
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
Other descriptive name: GZ402661
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)

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.

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

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 if there are qualitative differences between tolerability of the 2 dosing regimens and placebo
-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.

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

Secondary Outcome(s)

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

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.

Secondary ID(s)

2011-001480-42-ES

MIPO3801011/EFC12875

Source(s) of Monetary Support

Genzyme Corporation and its Affiliates