| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT00694109 | An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia | PHASE3 | COMPLETED | 144 | — | — | Apr 1, 2008 | Sep 1, 2014 | Sep 9, 2016 | 33 | United States, Brazil +5 |
| NCT00607373 | Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia | PHASE3 | COMPLETED | 51 | — | — | Jul 1, 2007 | Mar 1, 2009 | Sep 9, 2016 | 10 | United States, Brazil +5 |
| NCT00477594 | Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia | PHASE2 | COMPLETED | 21 | — | — | May 1, 2007 | Jul 1, 2011 | Sep 9, 2016 | 5 | United States |
| NCT00362180 | Measure Liver Fat Content After ISIS 301012 (Mipomersen) Administration | PHASE2 | COMPLETED | 38 | — | — | Jul 1, 2006 | Sep 1, 2010 | Oct 21, 2016 | 1 | Netherlands |
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
Baseline was defined as the last value prior to receiving the first dose of mipomersen in this study (for participants randomized to placebo in their index study and for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \>=6 months from their last dose of mipomersen in their index study), or the last value prior to receiving the first dose of mipomersen in their index study (for participants randomized to mipomersen in their index study and their first dose of mipomersen in this study was administered \<6 months from their last dose of mipomersen in their index study).
LDL-C was measured in mg/dL. Samples were taken following an overnight fast. For patients with triglycerides \<400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides \>=400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. If the Study Day 1 and screening LDL-C values were \>12% different (relative to the maximum value), then the screening value was not used, because the Study Day 1 value represents the best estimate of the patient's condition at the beginning of study drug administration. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
LDL cholesterol was measured in mg/dL. Samples were taken following an overnight fast. For patients with triglycerides \<400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides ≥400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
Samples were taken following an overnight fast. For patients with triglycerides \<400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides ≥400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. For patients who were on placebo in the index study or who took their last dose of mipomersen ≥6 months prior to first dose in this study, Baseline is defined as the last measurement prior to first dose in this study. For participants who took their last dose of mipomersen less than 6 months before starting this study, Baseline is defined as the last measurement taken prior to receiving a first dose in the index study.
Localized proton MRS was used to quantify liver TG concentration. All MRS imaging of the liver was performed using the same 1.5T scanner. The instructions were to cover the entire liver (from just above the dome to just below the inferior tip) using a qualified imaging technique (Yokoo, 2009, Radiology). Liver fat quantification was performed by determining the liver fat fraction (%) derived from MRS using selected Regions of Interest (ROI). The analyst typically looked for the branching of the right portal vein and mapped slices from one scan to the next. There were typically 2 ROIs in the right lobe and 1 in the left lobe. Magnetic resonance spectroscopy imaging ROIs between different scans were selected using anatomical landmarks for both time points.
| Arm | Type | Description |
|---|---|---|
| Mipomersen | EXPERIMENTAL | Mipomersen Sodium once a week for up to 4 years (depending on participant's consent). Participants were followed for additional 24 week post-treatment. |
| Placebo | PLACEBO_COMPARATOR | Participants received placebo as a subcutaneous injection once a week for 26 weeks. |
| Mipomersen 200 mg per week | EXPERIMENTAL | Participants received 200 mg mipomersen once a week by subcutaneous injection, for up to 3 years. |
| Mipomersen 200 mg every other week | EXPERIMENTAL | 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. |
| Cohort A: mipomersen | EXPERIMENTAL | Healthy volunteers treated with 6 injections of mipomersen 200 mg over the course of 4 weeks. Injections were given subcutaneously (sc) on days 1, 4, 8, 11, 15 and 22. |
| Cohort A: placebo | PLACEBO_COMPARATOR | Healthy volunteers treated with 6 injections of placebo over the course of 4 weeks. Injections were given subcutaneously (sc) on days 1, 4, 8, 11, 15 and 22. |
| Cohort D: mipomersen | EXPERIMENTAL | Participants with impaired fasting glucose and mixed dyslipidemia who were treated with 6 injections of mipomersen 200 mg over the course of 4 weeks. Injections were given subcutaneously (sc) on days 1, 4, 8, 11, 15 and 22. |
| Cohort D: placebo | PLACEBO_COMPARATOR | Participants with impaired fasting glucose and mixed dyslipidemia who were treated with 6 injections of placebo over the course of 4 weeks. Injections were given subcutaneously (sc) on days 1, 4, 8, 11, 15 and 22. |
| Cohort E: mipomersen | EXPERIMENTAL | Participants with uncomplicated heterozygous familial hypercholesterolemia (HeFH) treated with weekly mipomersen 200 mg injections for 13 weeks. |
| Cohort E: placebo | PLACEBO_COMPARATOR | Participants with uncomplicated heterozygous familial hypercholesterolemia (HeFH) treated with weekly placebo injections for 13 weeks. |
| Cohort F: no intervention | NO_INTERVENTION | A reference group of participants with familial hypobetalipoproteinemia (FBHL) who did not receive a study intervention. Data gathered for 15 weeks. |
| Cohort G: mipomersen | EXPERIMENTAL | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with mipomersen 200 mg weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
| Cohort G: placebo followed by mipomersen | PLACEBO_COMPARATOR | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with placebo weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
| Name | Type | Description |
|---|---|---|
| Mipomersen Sodium | DRUG | Subcutaneous injection as a single injection directly into the abdomen, thigh, or outer area of the upper arm. |
| mipomersen | DRUG | 200 mg mipomersen administered once a week for 26 weeks as a 1 mL subcutaneous injection. Subjects weighing less than 50 kg received a lower dose of 160 mg (0.8mL) mipomersen. |
| Placebo | DRUG | 1 mL subcutaneous injection once a week for 26 weeks. Subjects weighing less than 50 kg received 0.8 mL subcutaneous injection. |
Inclusion Criteria: * Satisfactory completion of dosing in their initial study (Protocol 301012-CS5 \[NCT00607373\], 301012-CS7 \[NCT00706849\], 301012-CS17 \[NCT00477594\], or MIPO3500108 \[NCT00794664\]) Exclusion Criteria: * Had any new condition or worsening of existing condition which in the...