Clinical trial NCT00477594: Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia
Official title: An Open-Label Extension Study to Assess the Long-term Safety and Efficacy of Mipomersen in Subjects With Familial Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Keywords: Familial Hypercholesterolemia
Heterozygous Familial Hypercholesterolemia
Homozygous Familial Hypercholesterolemia
ISIS 301012
mipomersen
Open Label Extension
Lead sponsor: Kastle Therapeutics, LLC
Sponsor class: INDUSTRY
Collaborators: name: Ionis Pharmaceuticals, Inc.
First posted: 2007-05-24
Enrollment: 21
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
timeFrame: Baseline and Weeks 52 and 104
measure: Low-density Lipoprotein Cholesterol (LDL-C) Over Time
timeFrame: Baseline and Weeks 52 and 104.
Secondary outcomes:
measure: Percent Change From Baseline in Apolipoprotein B
timeFrame: Baseline and Weeks 52 and 104
measure: Apolipoprotein B Over Time
timeFrame: Baseline and Weeks 52 and 104.
measure: Percent Change From Baseline in Total Cholesterol
timeFrame: Baseline and Weeks 52 and 104.
measure: Total Cholesterol Over Time
timeFrame: Baseline and Weeks 52 and 104.
measure: Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol
timeFrame: Baseline and Weeks 52 and 104.
measure: Non-High-Density Lipoprotein Cholesterol Over Time
timeFrame: Baseline and Weeks 52 and 104.
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs)
timeFrame: 2 years
measure: Percent Change From Baseline in Clinical Chemistry Parameters
timeFrame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.
measure: Percent Change From Baseline in Hematology Parameters
timeFrame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment
measure: Percent Change From Baseline in Blood Pressure
timeFrame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.
measure: Percent Change From Baseline in Pulse Rate
timeFrame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.
measure: Percent Change From Baseline in Respiratory Rate
timeFrame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.
Other outcomes:
measure: Percent Change From Baseline in Triglycerides
timeFrame: Baseline and Weeks 52 and 104.
measure: Triglycerides Over Time
timeFrame: Baseline and Weeks 52 and 104.
measure: Percent Change From Baseline in Lipoprotein(a)
timeFrame: Baseline and Weeks 52 and 104.
measure: Lipoprotein(a) Over Time
timeFrame: Baseline and Weeks 52 and 104.
measure: Percent Change From Baseline in Very-Low-Density Lipoprotein (VLDL) Cholesterol
timeFrame: Baseline and Weeks 52 and 104.
measure: Very-Low-Density Lipoprotein (VLDL) Cholesterol Over Time
timeFrame: Baseline and Weeks 52 and 104.
measure: Percent Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol
timeFrame: Baseline and Weeks 52 and 104.
measure: Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol Over Time
timeFrame: Baseline and Weeks 52 and 104.
measure: Percent Change From Baseline in Apolipoprotein A1
timeFrame: Baseline and Weeks 52 and 104.
measure: Apolipoprotein A1 Over Time
timeFrame: Baseline and Weeks 52 and 104.
measure: Percent Change From Baseline in High-Density Lipoprotein Cholesterol
timeFrame: Baseline and Weeks 52 and 104.
measure: High-Density Lipoprotein Cholesterol Over Time
timeFrame: Baseline and Weeks 52 and 104.
Locations:
city: Chicago
country: United States
state: Illinois
city: Auburn
country: United States
state: Maine
city: Biddeford
country: United States
state: Maine
city: Scarborough
country: United States
state: Maine
city: Cincinnati
country: United States
state: Ohio
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Patel N, Hegele RA. Mipomersen as a potential adjunctive therapy for hypercholesterolemia. Expert Opin Pharmacother. 2010 Oct;11(15):2569-72. doi: 10.1517/14656566.2010.512006.