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

Kastle Therapeutics

Status and phase: Completed; Phase 2

Conditions: Hyperlipoproteinemia Type II; Hyperlipidemias; Hypercholesterolemia; Genetic Diseases, Inborn; Congenital Abnormalities; Hyperlipoproteinemias; Metabolic Diseases; Hypercholesterolemia, Autosomal Dominant; Lipid Metabolism Disorders; Dyslipidemias; Metabolic Disorder; Metabolism, Inborn Errors; Lipid Metabolism, Inborn Errors; Infant, Newborn, Diseases

Treatments: Drug: mipomersen sodium

Study type: Interventional

Funder types: Industry

Identifiers

NCT00477594

2007-001024-12 (EudraCT Number)

301012-CS17

Details and patient eligibility

About

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.

Full 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.

Enrollment: 21 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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21 participants in 2 patient groups

Mipomersen 200 mg per week

Experimental group

Description:

Participants received 200 mg mipomersen once a week by subcutaneous injection, for up to 3 years.

Treatment:

Drug: mipomersen sodium

Mipomersen 200 mg every other week

Experimental group

Description:

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.

Treatment:

Drug: mipomersen sodium