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Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia

This study has been completed.
Sponsor:
Collaborator:
Isis Pharmaceuticals
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00477594
First received: May 22, 2007
Last updated: December 2, 2013
Last verified: December 2013

May 22, 2007
December 2, 2013
May 2007
March 2011   (final data collection date for primary outcome measure)
  • Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Baseline and Weeks 52 and 104 ] [ Designated as safety issue: No ]
    LDL cholesterol 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. For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
  • Low-density Lipoprotein Cholesterol (LDL-C) Over Time [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
    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. For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
To evaluate the safety and efficacy of extended dosing with ISIS 301012 in subjects with familial hypercholesterolemia on lipid-lowering therapy [ Time Frame: one year ]
Complete list of historical versions of study NCT00477594 on ClinicalTrials.gov Archive Site
  • Percent Change From Baseline in Apolipoprotein B [ Time Frame: Baseline and Weeks 52 and 104 ] [ Designated as safety issue: No ]
    Apolipoprotein B was measured in mg/dL. Samples were taken following an overnight fast. For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
  • Apolipoprotein B Over Time [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
    For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
  • Percent Change From Baseline in Total Cholesterol [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
    Total cholesterol was measured in mg/dL. Samples were taken following an overnight fast.
  • Total Cholesterol Over Time [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
    For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
  • Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
    Non-high-density lipoprotein cholesterol was measured in mg/dL. Samples were taken following an overnight fast.
  • Non-High-Density Lipoprotein Cholesterol Over Time [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
    For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    AEs were considered as related if assessed by the Investigator as possibly, probably or definitely related to study drug. The severity of each event was assessed using the following categories: Mild (symptom(s) barely noticeable to the patient or do not make the patient uncomfortable); Moderate (symptom(s) of a sufficient severity to make the patient uncomfortable, performance of daily activities is influenced) or Severe (symptom(s) of a sufficient severity to cause the patient severe discomfort, may cause cessation of treatment with the study drug). Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above.
  • Percent Change From Baseline in Clinical Chemistry Parameters [ Time Frame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment. ] [ Designated as safety issue: Yes ]
  • Percent Change From Baseline in Hematology Parameters [ Time Frame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment ] [ Designated as safety issue: Yes ]
  • Percent Change From Baseline in Blood Pressure [ Time Frame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment. ] [ Designated as safety issue: Yes ]
  • Percent Change From Baseline in Pulse Rate [ Time Frame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment. ] [ Designated as safety issue: Yes ]
  • Percent Change From Baseline in Respiratory Rate [ Time Frame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment. ] [ Designated as safety issue: Yes ]
Not Provided
  • Percent Change From Baseline in Triglycerides [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
    Triglycerides were measured in mg/dL. Samples were taken following an overnight fast.
  • Triglycerides Over Time [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
    For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
  • Percent Change From Baseline in Lipoprotein(a) [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
    Lipoprotein(a) was measured in mg/dL. Samples were taken following an overnight fast.
  • Lipoprotein(a) Over Time [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
    For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
  • Percent Change From Baseline in Very-Low-Density Lipoprotein (VLDL) Cholesterol [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
    Very-Low-Density Lipoprotein (VLDL) Cholesterol was measured in mg/dL. Samples were taken following an overnight fast.
  • Very-Low-Density Lipoprotein (VLDL) Cholesterol Over Time [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
    For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
  • Percent Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
  • Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol Over Time [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
    For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
  • Percent Change From Baseline in Apolipoprotein A1 [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
    Apolipoprotein A1 was measured in mg/dL. Samples were taken following an overnight fast.
  • Apolipoprotein A1 Over Time [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
    For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
  • Percent Change From Baseline in High-Density Lipoprotein Cholesterol [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
    High-Density Lipoprotein (HDL) Cholesterol was measured in mg/dL. Samples were taken following an overnight fast.
  • High-Density Lipoprotein Cholesterol Over Time [ Time Frame: Baseline and Weeks 52 and 104. ] [ Designated as safety issue: No ]
    For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
Not Provided
 
Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia
An Open-Label Extension Study to Assess the Long-term Safety and Efficacy of Mipomersen in Subjects With Familial Hypercholesterolemia

The purpose of this study is to evaluate the safety and efficacy of extended dosing of mipomersen in patients with familial hypercholesterolemia on lipid-lowering therapy who have completed either the 301012-CS8 (NCT00280995) or 301012-CS9 (NCT00281008) clinical drug trials.

Familial Hypercholesterolemia (FH) is an autosomal dominant metabolic disorder characterized by markedly elevated low density lipoprotein (LDL), premature onset of atherosclerosis, and development of xanthomata. There are two distinct subpopulations that have a high unmet medical need due to the lack of alternative therapy: homozygotes, who have two defective LDL receptor (LDL-R) genes, and heterozygotes with a history of cardiovascular disease (CVD) on maximally tolerated therapy. Treatment for FH is directed at lowering plasma levels of LDL-C.

Mipomersen is an antisense drug targeted to human apolipoprotein B (apoB), the principal apolipoprotein of atherogenic LDL-C and its metabolic precursor, very low density lipoprotein (VLDL). Mipomersen is complimentary to the coding region of the messenger ribonucleic acid (mRNA) for apo-B. Inhibition of apo-B would be expected to impair VLDL synthesis and result in lowered levels of LDL-C.

In early clinical trials, mipomersen has been shown to reduce levels of LDL-C to recommended target levels in some participants.

This was an open-label extension study, which consisted of a ≤2-week screening period, up to 3 years of treatment with mipomersen, and a 24-week post-treatment follow-up period. Patients who participated in Cohorts A, B, or C in study 301012-CS9 were randomized in a 1:1 ratio to mipomersen 200 mg once a week (QW) or 200 mg mipomersen every other week (QOW) for up to 3 years. Patients randomized to mipomersen 200 mg QOW were allowed to receive mipomersen 200 mg QW at the Investigator's discretion after the first 52 weeks of the treatment period. Patients who participated in study 301012-CS8 or Cohort D of study 301012-CS9 received 200 mg mipomersen QW for up to 3 years.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
200 mg/ml, in 1 ml solution for subcutaneous injection.
Other Names:
  • ISIS 301012
  • Kynamro™
  • Experimental: Mipomersen 200 mg per week
    Participants received 200 mg mipomersen once a week by subcutaneous injection, for up to 3 years.
    Intervention: Drug: mipomersen sodium
  • Experimental: Mipomersen 200 mg every other week
    Participants received 200 mg mipomersen every other week by subcutaneous injection, for up to 3 years. Participants could receive mipomersen 200 mg once a week at the Investigator's discretion after the first 52 weeks of the treatment period.
    Intervention: Drug: mipomersen sodium
Patel N, Hegele RA. Mipomersen as a potential adjunctive therapy for hypercholesterolemia. Expert Opin Pharmacother. 2010 Oct;11(15):2569-72. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21
July 2011
March 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

- Satisfactory completion of dosing and Week 7 or Week 15 assessments (depending on the treatment and dose received) in their initial study (Protocol 301012-CS8 (NCT00280995) or 301012-CS9 (NCT00281008)).

Exclusion Criteria:

- Have a new condition or worsening of existing condition which in the opinion of the Investigator would make the patient unsuitable for enrollment, or could interfere with patient's participation in or completion of the study.

Both
12 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00477594
301012-CS17, 2007-001024-12
No
Sanofi ( Genzyme, a Sanofi Company )
Genzyme, a Sanofi Company
Isis Pharmaceuticals
Study Director: Medical Monitor Genzyme, a Sanofi Company
Sanofi
December 2013

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