Phase 3
N=309
A Study of the Safety and Efficacy of Two Different Regimens of Mipomersen in Patients With Familial Hypercholesterolemia and Inadequately Controlled Low-Density Lipoprotein Cholesterol
Hypercholesterolemia · Heterozygous Familial
Bottom Line
View on ClinicalTrials.gov: NCT01475825 ↗Enrolled (actual)
309
Serious AEs
20.7%
Results posted
Mar 2019
Primary outcome: Primary: Percent Change From Baseline To Primary Endpoint Visit (PET) In LDL-C In Cohort 1 — -27.17; -6.77; -22.96; -10.62 Percent
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- mipomersen sodium 200 mg (Drug); Placebo (Drug); mipomersen sodium 70 mg (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Kastle Therapeutics, LLC
- Primary completion
- Dec 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline To Primary Endpoint Visit (PET) In LDL-C In Cohort 1 |
-27.17; -6.77; -22.96; -10.62 | — |
| SECONDARY Percent Change From Baseline To PET In LDL-C In Cohort 2 |
-31.20; -9.25; -43.60; -13.57 | — |
| SECONDARY Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 1 |
-24.14; -2.83; -21.43; -7.28 | — |
| SECONDARY Percent Change From Baseline To PET In Apolipoprotein B (Apo B) In Cohort 2 |
-30.76; -6.67; -36.34; -3.77 | — |
| SECONDARY Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 1 |
-18.84; -16.85; -27.18; -10.08 | — |
| SECONDARY Percent Change From Baseline To PET in Lipoprotein (a) In Cohort 2 |
-23.41; -11.86; -35.56; 18.79 | — |
Summary
Primary objective:
Determine whether mipomersen (ISIS 301012) significantly reduces atherogenic lipid levels in patients with severe heterozygous familial hypercholesterolemia (severe HeFH), defined as low-density lipoprotein cholesterol (LDL-C) levels ≥200 mg/dL plus the presence of coronary heart disease (CHD)/risk equivalents or LDL-C levels ≥300 mg/dL regardless of the presence of CHD/risk equivalents (referred to as Cohort 1) compared to placebo. Two different mipomersen dosing regimens will be studied: subcutaneous (SC) mipomersen 200 mg once weekly versus placebo, and SC mipomersen 70 mg thrice weekly versus placebo.
Secondary Objectives:
* Determine whether there are qualitative differences between the safety profiles of the 2 dosing regimens and placebo in Cohort 1, patients with HeFH with LDL-C levels ≥160 mg/dL and <200 mg/dL plus the presence of CHD/risk equivalents (referred to as Cohort 2), and the overall study population
* Determine whether there are qualitative differences between the tolerability of the 2 dosing regimens and placebo in Cohort 1, Cohort 2, and the overall study population
* Further characterize the pharmacokinetics (PK) of the 2 dosing regimens in Cohort 1, Cohort 2, and the overall study population
* Determine whether the 2 mipomersen dosing regimens significantly reduce atherogenic lipid levels in Cohort 2 compared to placebo
* Obtain additional data regarding ongoing safety and efficacy of mipomersen in patients with FH and inadequately controlled LDL-C who complete the primary efficacy assessment visit (PET) in the Blinded Treatment Period and continue treatment in Open-Label Continuation Period
Eligibility Criteria
Inclusion Criteria
- Diagnosis of severe hypercholesterolemia (LDL-C ≥300 mg/dL (7.77 mmol/L) or LDL-C ≥200 mg/dL (5.18 mmol/L) with documented coronary heart disease (CHD) or CHD risk equivalents, or diagnosis of Heterozygous Familial Hypercholesterolemia and LDL-C ≥160 mg/dL (4.14 mmol/L) and 6 weeks
Exclusion Criteria
- Significant health problems in the recent past including heart attack, stroke, coronary syndrome, unstable angina, heart failure, significant arrhythmia, hypertension, blood disorders, liver disease, cancer, digestive disorders, Type I diabetes, or uncontrolled Type II diabetes
- Apheresis within 3 months prior to Screening or expected to start apheresis during the treatment phase
Data sourced from ClinicalTrials.gov (NCT01475825). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.