Safety and Efficacy of Mipomersen in Patients With Severe Hypercholesterolemia on a Maximally Tolerated Lipid-Lowering Regimen and Who Are Not on Apheresis

Hypercholesterolemia Clinical Trial

Official title:

A Prospective Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Mipomersen in Patients With Severe Hypercholesterolemia on a Maximally Tolerated Lipid-Lowering Regimen and Who Are Not on Apheresis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00794664
• Other study ID #: MIPO3500108
• Secondary ID: 2008-006020-53
• Status: Completed
• Phase: Phase 3
• First received: November 19, 2008
• Last updated: October 27, 2014
• Start date: January 2009
• Est. completion date: October 2010

Study information

• Verified date: October 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaSouth Africa: Medicines Control CouncilCzech Republic: State Institute for Drug ControlGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the safety and efficacy of dosing with mipomersen for 26 weeks in treating severely hypercholesterolemic patients who are on a maximally tolerated lipid-lowering regimen and who are not on apheresis.

Description:

Hypercholesterolemia is characterized by markedly elevated low density lipoproteins (LDL). Elevated LDL is a major risk factor for coronary heart disease (CHD).

Mipomersen is an antisense drug that reduces a protein in the liver cells called apolipoprotein B (Apo-B). Apo-B plays a role in producing low density lipoprotein cholesterol (LDL-C) (the "bad" cholesterol) and moving it from the liver to one's bloodstream. High LDL-C is an independent risk factor for the development of coronary heart disease (CHD) or other diseases of blood vessels. It has been shown that lowering LDL-C reduces the risk of heart attacks and other major adverse cardiovascular events. The purpose of this study is to determine whether mipomersen safely and effectively lowers LDL-C in severely hypercholesterolemic patients who are on a maximally tolerated lipid-lowering regimen and who are not on apheresis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: October 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Fasting LDL-C =200 mg/dL (5.1 mmol/L) at screening and the presence of at least 1 of the following criteria:

• Myocardial infarction (MI)

• Percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)

• Coronary artery disease documented by angiography or any other accepted imaging technique

• Positive exercise test (=1 mm ST-depression at maximal exercise or test terminated because of angina) or a perfusion defect (e.g., thallium or single photon emission computed tomography)

• Other clinical atherosclerotic diseases: peripheral artery disease, symptomatic carotid artery disease, abdominal aortic aneurysm

• Or, if alternative above were not met, fasting LDL-C =300 mg/dL (7.8 mmol/L)

• On stable, maximally tolerated statin therapy for 8 weeks

• On stable, medication from an additional class of hypolipidemic agents for 8 weeks.

• On stable, low fat diet for 12 weeks

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Hypercholesterolemia
• Myocardial Ischemia

Intervention

Drug:
• Mipomersen
200 mg (1 mL), weekly subcutaneous injections for 26 weeks
• Placebo
1 mL weekly subcutaneous injections for 26 weeks

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company	Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Czech Republic,  Germany,  South Africa,  United Kingdom, 

References & Publications (1)

McGowan MP, Tardif JC, Ceska R, Burgess LJ, Soran H, Gouni-Berthold I, Wagener G, Chasan-Taber S. Randomized, placebo-controlled trial of mipomersen in patients with severe hypercholesterolemia receiving maximally tolerated lipid-lowering therapy. PLoS On — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage Change From Baseline in Triglycerides at Primary Efficacy Time Point (PET)	Triglycerides were measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Other	Triglycerides at Baseline and the Primary Efficacy Time Point (PET)	The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Other	Percentage Change From Baseline in Lipoprotein(a) at Primary Efficacy Time Point (PET)	Lipoprotein(a) was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Other	Lipoprotein(a) at Baseline and the Primary Efficacy Time Point (PET)	The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Other	Percentage Change From Baseline in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Primary Efficacy Time Point (PET)	VLDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Other	VLDL-C at Baseline and the Primary Efficacy Time Point (PET)	The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Other	Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol (LDL-C) to High-density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET)	LDL-C and HDL-C were measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Other	Ratio of LDL-C to HDL-C at Baseline and the Primary Efficacy Time Point (PET)	The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Other	Percent Change From Baseline in Apolipoprotein A1 (Apo-A1) at Primary Efficacy Time Point (PET)	Apo-A1 was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Other	Apo-A1 at Baseline and the Primary Efficacy Time Point (PET)	The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Other	Percentage Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET)	HDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Other	HDL-C at Baseline and the Primary Efficacy Time Point (PET)	The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Primary	Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Primary Efficacy Time Point	LDL-C was measured in mg/dL. Samples were taken following an overnight fast. For patients with triglycerides <400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides >=400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Primary	LDL-C at Baseline and the Primary Efficacy Time Point (PET)	The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Secondary	Percent Change From Baseline in Apolipoprotein B (Apo-B) at Primary Efficacy Time Point	Apo-B was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Secondary	Apo-B at Baseline and the Primary Efficacy Time Point (PET)	The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Secondary	Percentage Change From Baseline in Total Cholesterol at Primary Efficacy Time Point (PET)	Total cholesterol was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Secondary	Total Cholesterol at Baseline and the Primary Efficacy Time Point (PET)	The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Secondary	Percentage Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Primary Efficacy Time Point (PET)	Non-HDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No
Secondary	Non-HDL-C at Baseline and the Primary Efficacy Time Point (PET)	The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.	Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28	No