Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

Tracking Information
First Submitted Date  ICMJE June 5, 2008
First Posted Date  ICMJE June 10, 2008
Results First Submitted Date  ICMJE September 11, 2015
Results First Posted Date  ICMJE December 21, 2015
Last Update Posted Date September 9, 2016
Study Start Date  ICMJE April 2008
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 17, 2015)
  • 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).
  • 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).
  • 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).
  • 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).
Original Primary Outcome Measures  ICMJE
 (submitted: June 5, 2008)
To evaluate the safety and efficacy of extended dosing with ISIS 301012 in subjects with familial hypercholesterolemia on lipid-lowering therapy [ Time Frame: Through 26 weeks of treatment and through 24 weeks of follow up ]
Change History Complete list of historical versions of study NCT00694109 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2015)
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE 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®
Study Arms  ICMJE 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.
Intervention: Drug: Mipomersen Sodium
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 17, 2015)
144
Original Estimated Enrollment  ICMJE
 (submitted: June 5, 2008)
145
Actual Study Completion Date  ICMJE September 2014
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Canada,   Singapore,   South Africa,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00694109
Other Study ID Numbers  ICMJE 301012-CS6
2005-003450-10 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kastle Therapeutics, LLC
Study Sponsor  ICMJE Kastle Therapeutics, LLC
Collaborators  ICMJE Ionis Pharmaceuticals, Inc.
Investigators  ICMJE
Study Director: Medical Monitor Genzyme, a Sanofi Company
PRS Account Kastle Therapeutics, LLC
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP