Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia

NCT00477594 | Completed Phase 2 Results

• 2 other identifiers: 301012-CS172007-001024-12
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of extended dosing of mipomersen in patients with familial hypercholesterolemia on lipid-lowering therapy who have completed either the 301012-CS8 (NCT00280995) or 301012-CS9 (NCT00281008) clinical drug trials.

Conditions

Lipid Metabolism, Inborn Errors; Hypercholesterolemia, Autosomal Dominant; Hyperlipidemias; Metabolic Diseases; Hyperlipoproteinemia Type II; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Metabolic Disorder; Congenital Abnormalities; Hypercholesterolemia; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders

Keywords

Familial Hypercholesterolemia; Heterozygous Familial Hypercholesterolemia; Homozygous Familial Hypercholesterolemia; ISIS 301012; mipomersen; Open Label Extension

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)

  LDL cholesterol 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. For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.

  Baseline and Weeks 52 and 104

• Low-density Lipoprotein Cholesterol (LDL-C) Over Time

  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. For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.

  Baseline and Weeks 52 and 104.

Secondary Outcomes (12)

• Percent Change From Baseline in Apolipoprotein B

  Baseline and Weeks 52 and 104

• Apolipoprotein B Over Time

  Baseline and Weeks 52 and 104.

• Percent Change From Baseline in Total Cholesterol

  Baseline and Weeks 52 and 104.

• Total Cholesterol Over Time

  Baseline and Weeks 52 and 104.

• Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol

  Baseline and Weeks 52 and 104.

Other Outcomes (12)

• Percent Change From Baseline in Triglycerides

  Baseline and Weeks 52 and 104.

• Triglycerides Over Time

  Baseline and Weeks 52 and 104.

• Percent Change From Baseline in Lipoprotein(a)

  Baseline and Weeks 52 and 104.

Study Arms (2)

Mipomersen 200 mg per week

EXPERIMENTAL

Participants received 200 mg mipomersen once a week by subcutaneous injection, for up to 3 years.

Drug: mipomersen sodium

Mipomersen 200 mg every other week

EXPERIMENTAL

Participants received 200 mg mipomersen every other week by subcutaneous injection, for up to 3 years. Participants could receive mipomersen 200 mg once a week at the Investigator's discretion after the first 52 weeks of the treatment period.

Drug: mipomersen sodium

Interventions

mipomersen sodium DRUG

200 mg/ml, in 1 ml solution for subcutaneous injection.

Also known as: ISIS 301012, Kynamro™

Mipomersen 200 mg every other week; Mipomersen 200 mg per week

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Satisfactory completion of dosing and Week 7 or Week 15 assessments (depending on the treatment and dose received) in their initial study (Protocol 301012-CS8 (NCT00280995) or 301012-CS9 (NCT00281008)).

You may not qualify if:

• \- Have a new condition or worsening of existing condition which in the opinion of the Investigator would make the patient unsuitable for enrollment, or could interfere with patient's participation in or completion of the study.

Sponsors & Collaborators

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

Study Sites (5)

Unknown Facility

Chicago, Illinois, 60654, United States

Location

Unknown Facility

Auburn, Maine, 04210, United States

Location

Unknown Facility

Biddeford, Maine, 04005, United States

Location

Unknown Facility

Scarborough, Maine, 04074, United States

Location

Unknown Facility

Cincinnati, Ohio, 45212, United States

Location

Related Publications (1)

• 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

Lipid Metabolism, Inborn Errors; Hyperlipoproteinemia Type II; Hyperlipidemias; Metabolic Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Congenital Abnormalities; Hypercholesterolemia; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders; Homozygous Familial Hypercholesterolemia

Interventions

mipomersen

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; 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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2007
• First Posted: May 24, 2007
• Study Start: May 1, 2007
• Primary Completion: March 1, 2011
• Study Completion: July 1, 2011
• Last Updated: September 9, 2016
• Results First Posted: April 5, 2013

Record last verified: 2016-08

Locations

US (5)