Skip to main content
OpenTrials
Completed

NCT Number: NCT00607373

Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia

The purpose of this study is to evaluate the safety and efficacy of mipomersen (ISIS 301012) in subjects with homozygous familial hypercholesterolemia on lipid-lowering therapy.

This study consisted of a 26-week treatment period and a 24-week post-treatment follow-up period. Following treatment and Week 28 evaluations, participants could elect to enroll in an open-label extension study (301012-CS6; NCT00694109). Participants who were not eligible or elected not to enroll in the open-label extension study or who discontinued during the 28-week treatment period were followed in this study for 24 weeks from administration of the last dose of study drug.

Completed

Looking for future studies?

Notify Me

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

Loading trial locations.

About this study

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder of lipoprotein metabolism characterized by markedly elevated low density lipoprotein (LDL), premature onset of atherosclerosis and development of xanthomata. Patients with homozygous familial hypercholesterolemia (HoFH) have a severe disease that presents in childhood with total cholesterol typically in the 650 to 1000 mg/dL range.

This was a randomized, double-blind, placebo-controlled study, which consisted of a 4-week screening period, 26 weeks of treatment, and a 24-week post- treatment follow-up period (with the exception of patients who enrolled in the open-label extension study, Study 301012-CS6; NCT00694109). Eligible patients were randomized in a 2:1 ratio to receive 200 mg mipomersen or matching volume placebo subcutaneous (SC) injections weekly. Patients who weighed <50 kg received a lower dose of 160 mg mipomersen or matching volume of placebo SC injections weekly. Patients were to have been on a stable (>=12 weeks) regimen of allowed lipid-lowering therapies at screening, and were required to remain on the same dose and regimen throughout the study.

Patients returned to the study center for clinical evaluation every other week during the first 4 weeks of treatment, once every 4 to 5 weeks for the remainder of the treatment period, and monthly during the post-treatment evaluation (follow-up) period. The primary endpoint assessment was at Week 28. Following treatment and Week 28 evaluations, eligible patients who tolerated the study drug could elect to enroll in the open-label extension study (Study 301012-CS6; NCT00694109). Patients who did not participate in the open-label extension study were required to return to the study center for clinical evaluation at least twice during the post-treatment follow-up period, including an end-of-study termination visit at the end of this 24-week period.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Diagnosis of Homozygous Familial Hypercholesterolemia (HoFH)
  • Stable lipid-lowering therapy for 12 weeks
  • Stable weight for 6 weeks
  • Stable low fat diet for 8 weeks

Exclusion criteria

  • Significant health problems in the recent past including heart attack, stroke, blood disorders, cancer, or digestive problems

Treatment and study plan

mipomersen

Drug

200 mg mipomersen administered once a week for 26 weeks as a 1 mL subcutaneous injection. Subjects weighing less than 50 kg received a lower dose of 160 mg (0.8mL) mipomersen.

Other names: ISIS 301012, mipomersen sodium, Kynamro™

Placebo

Drug

1 mL subcutaneous injection once a week for 26 weeks. Subjects weighing less than 50 kg received 0.8 mL subcutaneous injection.

Primary outcomes

  1. Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Primary Efficacy Time Point

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    LDL-C 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. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. If the Study Day 1 and screening LDL-C values were >12% different (relative to the maximum value), then the screening value was not used, because the Study Day 1 value represents the best estimate of the patient's condition at the beginning of study drug administration. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  2. LDL-C at Baseline and the Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Secondary outcomes

  1. Percent Change From Baseline in Apolipoprotein B (Apo-B) at Primary Efficacy Time Point

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    Apo-B was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  2. Apo-B at Baseline and the Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 )

    The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  3. Percentage Change From Baseline in Total Cholesterol at Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    Total cholesterol was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  4. Total Cholesterol at Baseline and the Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  5. Percentage Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    Non-HDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  6. Non-HDL-C at Baseline and the Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Other outcomes

  1. Percentage Change From Baseline in Triglycerides at Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    Triglycerides were measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  2. Triglycerides at Baseline and the Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  3. Percentage Change From Baseline in Lipoprotein(a) at Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    Lipoprotein(a) was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  4. Lipoprotein(a) at Baseline and the Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  5. Percentage Change From Baseline in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    VLDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  6. VLDL-C at Baseline and the Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  7. Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol (LDL-C) to High-density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    LDL-C and HDL-C were measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  8. Ratio of LDL-C to HDL-C at Baseline and the Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  9. Percent Change From Baseline in Apolipoprotein A1 (Apo-A1) at Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    Apo-A1 was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  10. Apo-A1 at Baseline and the Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  11. Percentage Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    HDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

  12. HDL-C at Baseline and the Primary Efficacy Time Point (PET)

    Time frame: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

    The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Sponsors and collaborators

Lead sponsor

Kastle Therapeutics, LLC

Industry

Collaborators

  • Ionis Pharmaceuticals, Inc.

Registry information

Official study title

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Mipomersen as Add-on Therapy in Homozygous Familial Hypercholesterolemia Subjects

Acronym: RADICHOL 1

Important dates

Study start
2007
Primary completion
2009
Study completion
2009
First posted
Feb 5, 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.

Related clinical trials

Published trials that share one or more normalized conditions with this study.