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NCT Number: NCT00694109

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

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.

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Key information

Conditions

Lipid Metabolism, Inborn Errors Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Dyslipidemias Genetic Diseases, Inborn Homozygous Familial Hypercholesterolemia Hypercholesterolemia Hypercholesterolemia, Autosomal Dominant Hyperlipidemias Hyperlipoproteinemia Type II Hyperlipoproteinemias Infant, Newborn, Diseases Lipid Metabolism Disorders Metabolic Diseases Metabolic Disorder Metabolism, Inborn Errors Nutritional and Metabolic Diseases

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

São Paulo, Brazil

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

mipomersen sodium

Drug

Subcutaneous injection as a single injection directly into the abdomen, thigh, or outer area of the upper arm.

Other names: ISIS 301012, Kynamro®

Primary outcomes

  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 outcomes

  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).

Sponsors and collaborators

Lead sponsor

Kastle Therapeutics, LLC

Industry

Collaborators

  • Ionis Pharmaceuticals, Inc.

Registry information

Official study 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

Important dates

Study start
2008
Primary completion
2014
Study completion
2014
First posted
Jun 10, 2008
Registry last updated
Sep 9, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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