Safety and Efficacy Study of ISIS 301012 (Mipomersen) Administration in High Risk Statin Intolerant Subjects

NCT00707746 | Completed Phase 2 Results

• 2 other identifiers: 301012-CS192007-005140-24
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine safety and efficacy of mipomersen (ISIS 301012) in the reduction of total cholesterol, low density lipoprotein cholesterol (LDL-C), and apolipoprotein B (apoB) in high risk subjects intolerant to statins.

Conditions

Metabolic Diseases; Hyperlipidemias; Metabolic Disorder; Hypercholesterolemia; Dyslipidemias; Lipid Metabolism Disorders

Keywords

statin intolerant; hypercholesterolemia

Outcome Measures

Primary Outcomes (3)

• Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the 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. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.

  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).

• Low-density Lipoprotein Cholesterol at Baseline and the Primary Efficacy Time Point

  The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.

  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).

• Summary of Participants With Adverse Events

  The on-treatment time frame spanned the time during which the study drug was administered until the later of the primary efficacy time point and 14 days beyond the last study drug date. Adverse events (AEs) were considered related if assessed by the Investigator as possibly, probably or definitely related to study drug. Severity was assessed as: * Mild-symptom barely noticeable to the patient or do not make the patient uncomfortable; * Moderate-symptom makes the patient uncomfortable, affects performance of daily activities; * Severe-symptom causes the patient severe discomfort, may cause cessation of treatment with the study drug. Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention.

  Pre-treatment (prior to first dose), On-treatment (Day 1 to week 28), Post-treatment (Week 28-52)

Secondary Outcomes (6)

• Percent Change From Baseline in Apolipoprotein B at the Primary Efficacy Time Point

  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).

• Apolipoprotein B at Baseline and at the Primary Efficacy Time Point

  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).

• Percent Change From Baseline in Total Cholesterol at the Primary Efficacy Time Point

  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).

• Total Cholesterol at Baseline and at the Primary Efficacy Time Point

  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).

• Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol at the Primary Efficacy Time Point

  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 (12)

• Percent Change From Baseline in Triglycerides at the Primary Efficacy Time Point

  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).

• Triglycerides at Baseline and at the Primary Efficacy Time Point

  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).

• Percent Change From Baseline in Lipoprotein (a) at the Primary Efficacy Time Point

  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).

Study Arms (2)

Placebo

PLACEBO COMPARATOR

1 mL placebo saline, weekly subcutaneous injections for 26 weeks

Drug: placebo

Mipomersen

EXPERIMENTAL

200 mg (1 mL), weekly subcutaneous injections for 26 weeks

Drug: mipomersen

Interventions

mipomersen DRUG

Also known as: ISIS 301012, mipomersen sodium, Kynamro™

Mipomersen

placebo DRUG

Also known as: placebo saline

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of statin intolerance
• Diagnosis of Coronary Artery Disease (CAD)
• Diagnosis of hypercholesterolemia
• Stable weight for \> 6 weeks

You may not qualify if:

• Significant health problems in the recent past (≤24 weeks) including heart attack, heart surgery, heart failure, uncontrolled hypothyroidism, blood disorders, digestive problems, disease of central nervous system, cancer, liver or renal disease

Sponsors & Collaborators

• Kastle Therapeutics, LLC: lead
• Ionis Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Unknown Facility

Amsterdam, 1105AZ, Netherlands

Location

Related Publications (2)

• Visser ME, Wagener G, Baker BF, Geary RS, Donovan JM, Beuers UH, Nederveen AJ, Verheij J, Trip MD, Basart DC, Kastelein JJ, Stroes ES. Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial. Eur Heart J. 2012 May;33(9):1142-9. doi: 10.1093/eurheartj/ehs023. Epub 2012 Apr 16.

  PMID: 22507979 DERIVED

• Patel N, Hegele RA. Mipomersen as a potential adjunctive therapy for hypercholesterolemia. Expert Opin Pharmacother. 2010 Oct;11(15):2569-72. doi: 10.1517/14656566.2010.512006.

  PMID: 20707601 DERIVED

MeSH Terms

Conditions

Metabolic Diseases; Hyperlipidemias; Hypercholesterolemia; Dyslipidemias; Lipid Metabolism Disorders

Interventions

mipomersen

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Genzyme Medical Information
• Organization: Genzyme Corporation

617-252-7832

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2008
• First Posted: July 1, 2008
• Study Start: October 1, 2008
• Primary Completion: August 1, 2010
• Study Completion: January 1, 2011
• Last Updated: September 9, 2016
• Results First Posted: April 5, 2013

Record last verified: 2016-08

Locations

NL (1)