Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia (RADICHOL 1)

Kastle Therapeutics

Status and phase: Completed; Phase 3

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: Placebo; Drug: mipomersen

Study type: Interventional

Funder types: Industry

Identifiers

NCT00607373

2005-003449-15 (EudraCT Number)

301012CS5

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 51 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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51 participants in 2 patient groups, including a placebo group

Mipomersen

Experimental group

Description:

Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.

Treatment:

Drug: mipomersen

Placebo

Placebo Comparator group

Description:

Participants received placebo as a subcutaneous injection once a week for 26 weeks.

Treatment:

Drug: Placebo