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Trial record 7 of 19 for:    MIPOMERSEN

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00694109
Recruitment Status : Completed
First Posted : June 10, 2008
Results First Posted : December 21, 2015
Last Update Posted : September 9, 2016
Sponsor:
Collaborator:
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Kastle Therapeutics, LLC

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

Condition or disease Intervention/treatment 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

Detailed Description:
All familial hypercholesterolemia (FH) or severe hypercholesterolemia participants who had tolerated the treatment regimen in Protocol 301012-CS5 (NCT00607373), 301012-CS7 (NCT00706849) or MIPO3500108 (NCT00794664) and satisfactorily completed the study through to Week 28 were eligible for participation in this open label treatment extension study for up to 4 years or until mipomersen was commercially available, whichever comes first. Consenting participants who had 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 was commercially available, whichever comes first. All participants, who entered the study, received 200 mg mipomersen (ISIS 301012) subcutaneously (s.c.) every week, including those who were randomized to placebo in their initial study. Participants who were originally enrolled in Protocol 301012-CS5 (NCT00607373) and weighed <50 kg received 160 mg every week. Dose adjustments (70 mg injections administered three times per week, on separate days) were allowed for participants who were not tolerating or who 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, 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 was to be performed every 4-10 weeks during the treatment period. Plasma trough mipomersen (ISIS 301012) levels was to be measured to estimate exposure. Participants who completed dosing or who discontinued prematurely from the study for any reason was 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. Participants were required to return to the study center for clinical evaluation and clinical laboratory tests every 8 weeks during the safety follow-up period.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 144 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : April 2008
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2014


Arm Intervention/treatment
Experimental: Mipomersen
Mipomersen Sodium once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment.
Drug: Mipomersen Sodium
Subcutaneous injection as a single injection directly into the abdomen, thigh, or outer area of the upper arm.
Other Names:
  • ISIS 301012
  • Kynamro®




Primary Outcome Measures :
  1. Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  2. Percent Change From Baseline in Apolipoprotein B (Apo B) [ Time Frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  3. Percent Change From Baseline in Total Cholesterol [ Time Frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  4. Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) [ Time Frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).


Secondary Outcome Measures :
  1. Percent Change From Baseline in Triglycerides [ Time Frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  2. Percent Change From Baseline in Lipoprotein (a) [ Time Frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  3. Percent Change From Baseline in LDL Particles' Size (Total) [ Time Frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  4. Percent Change From Baseline in LDL Particles' Size (Large) [ Time Frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  5. Percent Change From Baseline in LDL Particles' Size (Medium) [ Time Frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  6. Percent Change From Baseline in LDL Particles' Size (Small) [ Time Frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  7. Percent Change From Baseline in LDL Particles' Size (Very Small) [ Time Frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  8. Percent Change From Baseline in HDL Particles' Size (Large) [ Time Frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  9. Percent Change From Baseline in HDL Particles' Size (Medium) [ Time Frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  10. Percent Change From Baseline in HDL Particles' Size (Small) [ Time Frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  11. Percent Change From Baseline in Intermediate Density Lipoprotein Particles' Size [ Time Frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  12. Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Particles' Size (Large) and Chylomicron Particles' Size [ Time Frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  13. Percent Change From Baseline in VLDL Particles' Size (Medium) [ Time Frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  14. Percent Change From Baseline in VLDL Particles' Size (Small) [ Time Frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  15. Percent Change From Baseline in Total VLDL Particles' Size and Chylomicron Particles' Size [ Time Frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  16. Change From Baseline in C-Reactive Protein [ Time Frame: Baseline up to End of treatment; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).

  17. Percent Change From Baseline in Apolipoprotein A-1 [ Time Frame: Baseline up to Week 234; 24 weeks post treatment (up to 4.5 years) ]
    Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered >=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered <6 months from their last dose of mipomersen in their index study).



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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:

  • Had any new condition or worsening of existing condition which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00694109


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Locations
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United States, California
Mission Viejo, California, United States, 92691
Newport Beach, California, United States, 92660
United States, Connecticut
Bridgeport, Connecticut, United States, 06606
United States, Florida
Melbourne, Florida, United States, 32901
Winter Park, Florida, United States, 32792
United States, Illinois
Chicago, Illinois, United States, 60654
United States, Kansas
Kansas City, Kansas, United States, 66160
United States, Maine
Biddeford, Maine, United States, 04005
United States, Massachusetts
Boston, Massachusetts, United States, 02114
United States, Missouri
St Louis, Missouri, United States, 63110
United States, New Hampshire
Concord, New Hampshire, United States, 03301
United States, New York
New York, New York, United States, 10032
United States, North Carolina
Charlotte, North Carolina, United States, 28204
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati, Ohio, United States, 45212
Franklin, Ohio, United States, 45005
United States, Oregon
Portland, Oregon, United States, 97239
United States, Tennessee
Nashville, Tennessee, United States, 37232
United States, Texas
Dallas, Texas, United States, 75226
United States, Washington
Seattle, Washington, United States, 98104
Brazil
Sao Paulo, Brazil
Canada, Manitoba
Winnipeg, Manitoba, Canada, R3A 1M5
Canada, Ontario
London, Ontario, Canada, N6A 5K8
Canada, Quebec
Chicoutimi, Quebec, Canada, G7H 5H6
Montreal, Quebec, Canada, H1T 1C8
Montreal, Quebec, Canada, H2W 1R7
Sherbrooke, Quebec, Canada, J1H 5N4
Canada
Quebec, Canada, G1V 4M6
Singapore
Singapore, Singapore, 168752
South Africa
Observatory, South Africa, 7925
Parktown, South Africa, 2193
Taiwan
Taipei, Taiwan, 11217
United Kingdom
London, United Kingdom, WC1N 3BG
Sponsors and Collaborators
Kastle Therapeutics, LLC
Ionis Pharmaceuticals, Inc.
Investigators
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Study Director: Medical Monitor Genzyme, a Sanofi Company

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Kastle Therapeutics, LLC
ClinicalTrials.gov Identifier: NCT00694109     History of Changes
Other Study ID Numbers: 301012-CS6
2005-003450-10 ( EudraCT Number )
First Posted: June 10, 2008    Key Record Dates
Results First Posted: December 21, 2015
Last Update Posted: September 9, 2016
Last Verified: August 2016
Keywords provided by Kastle Therapeutics, LLC:
Familial Hypercholesterolemia
FH
Heterozygous Familial Hypercholesterolemia
HeFH
Homozygous Familial Hypercholesterolemia
HoFH
Additional relevant MeSH terms:
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Mipomersen
Congenital Abnormalities
Hyperlipoproteinemia Type II
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Infant, Newborn, Diseases
Lipid Metabolism, Inborn Errors
Hypercholesterolemia
Dyslipidemias
Hyperlipidemias
Hyperlipoproteinemias
Metabolic Diseases
Lipid Metabolism Disorders
Disease
Pathologic Processes
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents