Study of ISIS 301012 (Mipomersen) in Heterozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy

Study Overview
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Brief Summary
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The aim of this study is to assess the safety and efficacy of varying doses of ISIS 301012 (mipomersen) as add-on therapy in subjects with Heterozygous Familial Hypercholesterolemia

Official Title
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A Phase 2, Double-Blind, Placebo-Controlled, Dose Escalation Study to Assess the Safety, Efficacy, and Pharmacokinetics of ISIS 301012 as Add-on Therapy in Heterozygous Familial Hypercholesterolemia Subjects

Conditions
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Hypercholesterolemia, Familial

Intervention / Treatment
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* Drug: ISIS 301012 or Placebo
* Drug: ISIS 301012 or Placebo
* Drug: ISIS 301012 or Placebo
* Drug: ISIS 301012 or Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Weight ≥ 50 kg Diagnosis of Heterozygous Familial Hypercholesterolemia. Females must be non-pregnant and non-lactating. On stable lipid lowering therapy for at least 4 weeks. Lipid levels meet the pre-specified criteria. Exclusion Criteria: Subject had heart problems in the prior 6 months. Subject has elevated ALT, AST, or CPK. History of renal disease, liver disease, or malignancy. Use of oral anticoagulants, unless the dose has been stable for 4 weeks Have any other conditions, which in the opinion of the Investigator would make the subject unsuitable for enrollment, or could interfere with the subject participating in or completing the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>Loading doses followed by weekly maintenance doses | Drug: ISIS 301012 or Placebo<br>* 50 mg subcutaneous injections on days 1, 4, 8, 11, 15, 22, 29, and 36<br>|
| Experimental: Cohort B<br>Loading doses followed by weekly maintenance doses | Drug: ISIS 301012 or Placebo<br>* 100 mg subcutaneous injections on days 1, 4, 8, 11, 15, 22, 29, and 36<br>|
| Experimental: Cohort C<br>Loading doses followed by weekly maintenance doses | Drug: ISIS 301012 or Placebo<br>* 200 mg subcutaneous injections on days 1, 4, 8, 11, 15, 22, 29, and 36<br>|
| Experimental: Cohort D<br>Loading doses followed by extended weekly maintenance doses | Drug: ISIS 301012 or Placebo<br>* 300 mg subcutaneous injections on days 1, 4, 8, 11, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, and 85<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent reduction in LDL-cholesterol from baseline |  | Week 7 (Cohorts A-C), Week 15 (Cohort D) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LDL-cholesterol, apoB-100, Heterozygous Familial Hypercholesterolemia