Clinical trial NCT00770146: Safety and Efficacy of Mipomersen (ISIS 301012) As Add-on Therapy in High Risk Hypercholesterolemic Patients
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) as Add-on Therapy in High Risk Hypercholesterolemic Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Coronary Heart Disease
Lead sponsor: Kastle Therapeutics, LLC
Sponsor class: INDUSTRY
Collaborators: name: Ionis Pharmaceuticals, Inc.
First posted: 2008-10-09
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficacy of dosing with mipomersen for 26 weeks in patients with high cholesterol who are on a maximally tolerated dose of statin and who have a diagnosis that puts them at least at high risk of coronary heart disease (CHD).

Detailed description: Hypercholesterolemia is characterized by markedly elevated low density lipoproteins (LDL). Elevated LDL is a major risk factor for 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 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 patients with high cholesterol who are at high risk for CHD and who are already on the maximally tolerated dose of statin.

This study consisted of a 26-week treatment period and a 24-week post-treatment follow-up period. Participants who finished treatment or who discontinued prematurely from the study for any reason were assessed for safety for 24 weeks after the last study drug dose.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of hypercholesterolemia (LDL-C ≥ 100 mg/dL)
* At high risk of CHD
* On stable, maximally tolerated statin therapy 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, liver disease, cancer, type I diabetes.

Primary outcomes:
measure: Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
measure: Low-density Lipoprotein Cholesterol (LDL-C) at Baseline and at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Secondary outcomes:
measure: Percent Change From Baseline in Apolipoprotein B at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
measure: Apolipoprotein B at Baseline and at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
measure: Percent Change From Baseline in Total Cholesterol at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
measure: Total Cholesterol at Baseline and at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
measure: Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
measure: Non-High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Other outcomes:
measure: Percent Change From Baseline in Triglycerides at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
measure: Triglycerides at Baseline and at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
measure: Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
measure: High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
measure: Percent Change From Baseline in Lipoprotein (a) at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
measure: Lipoprotein (a) at Baseline and at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
measure: Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
measure: Very Low Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
measure: Percent Change From Baseline in the Ratio of LDL Cholesterol to HDL Cholesterol at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
measure: Ratio of LDL Cholesterol to HDL Cholesterol at Baseline and at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
measure: Percent Change From Baseline in Apolipoprotein A1 at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
measure: Apolipoprotein A1 at Baseline and at the Primary Efficacy Time Point
timeFrame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Locations:
city: Birmingham
country: United States
state: Alabama
city: Birmingham
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Muscle Shoals
country: United States
state: Alabama
city: Litchfield Park
country: United States
state: Arizona
city: Beverly Hills
country: United States
state: California
city: Escondido
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Mission Viejo
country: United States
state: California
city: Newport Beach
country: United States
state: California
city: San Diego
country: United States
state: California
city: Santa Rosa
country: United States
state: California
city: Thousand Oaks
country: United States
state: California
city: Westlake Village
country: United States
state: California
city: Aventura
country: United States
state: Florida
city: Inverness
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Longwood
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Pensacola
country: United States
state: Florida
city: Ponte Verda
country: United States
state: Florida
city: Port Orange
country: United States
state: Florida
city: Sandy Springs
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Chicago
country: United States
state: Illinois
city: Bloomingtom
country: United States
state: Indiana
city: Evansville
country: United States
state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Louisville
country: United States
state: Kentucky
city: Baltimore
country: United States
state: Maryland
city: Brockton
country: United States
state: Massachusetts
city: New Bedford
country: United States
state: Massachusetts
city: Edina
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: Berlin
country: United States
state: New Jersey
city: Johnson City
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Greenville
country: United States
state: North Carolina
city: Wilson
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Mentor
country: United States
state: Ohio
city: Norman
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Lansdale
country: United States
state: Pennsylvania
city: Murrells Inlet
country: United States
state: South Carolina
city: Simpsonville
country: United States
state: South Carolina
city: Spartanburg
country: United States
state: South Carolina
city: Rapid City
country: United States
state: South Dakota
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Grapevine
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Olympia
country: United States
state: Washington
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Santos RD, Raal FJ, Catapano AL, Witztum JL, Steinhagen-Thiessen E, Tsimikas S. Mipomersen, an antisense oligonucleotide to apolipoprotein B-100, reduces lipoprotein(a) in various populations with hypercholesterolemia: results of 4 phase III trials. Arterioscler Thromb Vasc Biol. 2015 Mar;35(3):689-99. doi: 10.1161/ATVBAHA.114.304549. Epub 2015 Jan 22.
citation: Thomas GS, Cromwell WC, Ali S, Chin W, Flaim JD, Davidson M. Mipomersen, an apolipoprotein B synthesis inhibitor, reduces atherogenic lipoproteins in patients with severe hypercholesterolemia at high cardiovascular risk: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol. 2013 Dec 10;62(23):2178-84. doi: 10.1016/j.jacc.2013.07.081. Epub 2013 Sep 4.