An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Isis Pharmaceuticals
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00694109
First received: June 5, 2008
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

To evaluate the safety and efficacy of extended dosing with mipomersen (ISIS 301012) in patients with familial hypercholesterolemia or severe hypercholesterolemia on lipid-lowering therapy who have completed either the 301012-CS5 (NCT00607373), 301012-CS7 (NCT00706849), 301012-CS17 (NCT00477594) or MIPO3500108 (NCT00794664) clinical drug trials.


Condition Intervention Phase
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
Drug: mipomersen sodium
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percent reduction of low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo-B), total cholesterol and non-high-density lipoprotein cholesterol (non-HDL-C) at various timepoints [ Time Frame: Through up to four years of treatment and 24 weeks of follow-up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effects of mipomersen (ISIS 301012) on triglycerides, very-low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A-1 (apoA-1), lipoprotein (a) (Lp(a), lipoprotein sub-classes and high-sensitivity C-Reactive Protein [ Time Frame: Through up to four years of treatment and 24 weeks of follow-up ] [ Designated as safety issue: No ]

Enrollment: 145
Study Start Date: April 2008
Estimated Study Completion Date: September 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 200 mg mipomersen Drug: mipomersen sodium
200 mg mipomersen (ISIS 301012) subcutaneous injections (s.c.) every week (or if subjects weighing < 50 kg will receive 160 mg every week)
Other Name: ISIS 301012

Detailed Description:

All familial hypercholesterolemia (FH) or severe hypercholesterolemia patients who have tolerated the treatment regimen in Protocol 301012-CS5 (NCT00607373), 301012-CS7 (NCT00706849) or MIPO3500108 (NCT00794664) and satisfactorily completed the study through to Week 28 are eligible for participation in this open label treatment extension study for up to 4 years or until mipomersen is commercially available, whichever comes first. Consenting patients who have tolerated mipomersen and satisfactorily completed 301012-CS17 (NCT00477594) through Year 3 may also enroll for up to an additional 2 years of treatment in this study or until mipomersen is commercially available, whichever comes first. All patients who enter the study will receive 200 mg mipomersen (ISIS 301012) subcutaneously (s.c.) every week, including those who were randomized to placebo in their initial study. Patients who were originally enrolled in Protocol 301012-CS5 (NCT00607373) and weigh < 50 kg will receive 160 mg every week. Dose adjustments (70 mg injections administered three times per week, on separate days) are allowed for patients who are not tolerating or who have had previous issues with tolerating the once a week injections due to injection site reactions (ISRs) or flu-like symptoms. Study visits and clinical lab assessments including hematology with differential, chemistry, serum lipid panel (total cholesterol, low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB), apoA-1, triglycerides (TG) and Lp(a), and urinalysis will be performed every 4-10 weeks during the treatment period. Plasma trough mipomersen (ISIS 301012) levels will be measured to estimate exposure. Subjects who complete dosing or who discontinue prematurely from the study for any reason will be followed for safety for 24 weeks (safety follow-up period) after their last dose of mipomersen (ISIS 301012) or longer in the case of a significant adverse events (AE) or abnormal biochemical or clinical finding. Subjects will be required to return to the study center for clinical evaluation and clinical laboratory tests every 8 weeks during the safety follow-up period.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Satisfactory completion of dosing in their initial study (Protocol 301012-CS5 (NCT00607373), 301012-CS7 (NCT00706849), 301012-CS17 (NCT00477594), or MIPO3500108 (NCT00794664)).

Exclusion Criteria:

  • Have any new condition or worsening of existing condition which in the opinion of the Investigator would make the subject unsuitable for enrollment, or could interfere with the subject participating in or completing the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00694109

  Show 33 Study Locations
Sponsors and Collaborators
Genzyme, a Sanofi Company
Isis Pharmaceuticals
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided

Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00694109     History of Changes
Other Study ID Numbers: 301012-CS6, 2005-003450-10
Study First Received: June 5, 2008
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
South Africa: Medicines Control Council
Taiwan: Department of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Brazil: National Health Surveillance Agency
Singapore: Health Sciences Authority

Keywords provided by Sanofi:
Familial Hypercholesterolemia
FH
Heterozygous Familial Hypercholesterolemia
HeFH
Homozygous Familial Hypercholesterolemia
HoFH

Additional relevant MeSH terms:
Lipid Metabolism, Inborn Errors
Congenital Abnormalities
Genetic Diseases, Inborn
Hypercholesterolemia
Hyperlipoproteinemia Type II
Hyperlipidemias
Hyperlipoproteinemias
Infant, Newborn, Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Lipid Metabolism Disorders
Sphingolipidoses
Dyslipidemias
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Lipidoses
Lysosomal Storage Diseases
Mipomersen
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Molecular Probes

ClinicalTrials.gov processed this record on August 25, 2014