Congenital Abnormalities, Dyslipidemias, Genetic Diseases, Inborn, Hypercholesterolemia, Hypercholesterolemia, Autosomal Dominant, Hyperlipidemias, Hyperlipoproteinemias, Hyperlipoproteinemia Type II, Infant, Newborn, Diseases, Lipid Metabolism Disorders, Lipid Metabolism, Inborn Errors, Metabolic Diseases, Metabolic Disorder, Metabolism, Inborn Errors
Conditions
Keywords
Familial Hypercholesterolemia, Heterozygous Familial Hypercholesterolemia, Homozygous Familial Hypercholesterolemia, ISIS 301012, mipomersen, Open Label Extension
Brief summary
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.
Detailed 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.
Interventions
200 mg/ml, in 1 ml solution for subcutaneous injection.
Sponsors
Ionis Pharmaceuticals, Inc.
Kastle Therapeutics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Baseline and Weeks 52 and 104 | 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. |
| Low-density Lipoprotein Cholesterol (LDL-C) Over Time | Baseline and Weeks 52 and 104. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apolipoprotein B Over Time | Baseline and Weeks 52 and 104. | 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. |
| Percent Change From Baseline in Apolipoprotein B | Baseline and Weeks 52 and 104 | Apolipoprotein B was measured in mg/dL. Samples were taken following an overnight fast. 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. |
| Percent Change From Baseline in Total Cholesterol | Baseline and Weeks 52 and 104. | Total cholesterol was measured in mg/dL. Samples were taken following an overnight fast. |
| Total Cholesterol Over Time | Baseline and Weeks 52 and 104. | 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. |
| Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol | Baseline and Weeks 52 and 104. | Non-high-density lipoprotein cholesterol was measured in mg/dL. Samples were taken following an overnight fast. |
| Non-High-Density Lipoprotein Cholesterol Over Time | Baseline and Weeks 52 and 104. | 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. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) | 2 years | AEs were considered as related if assessed by the Investigator as possibly, probably or definitely related to study drug. The severity of each event was assessed using the following categories: Mild (symptom(s) barely noticeable to the patient or do not make the patient uncomfortable); Moderate (symptom(s) of a sufficient severity to make the patient uncomfortable, performance of daily activities is influenced) or Severe (symptom(s) of a sufficient severity to cause the patient severe discomfort, may cause cessation of treatment with the study drug). Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above. |
| Percent Change From Baseline in Clinical Chemistry Parameters | Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment. | — |
| Percent Change From Baseline in Hematology Parameters | Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment | — |
| Percent Change From Baseline in Blood Pressure | Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment. | — |
| Percent Change From Baseline in Pulse Rate | Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment. | — |
| Percent Change From Baseline in Respiratory Rate | Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment. | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Lipoprotein(a) | Baseline and Weeks 52 and 104. | Lipoprotein(a) was measured in mg/dL. Samples were taken following an overnight fast. |
| Lipoprotein(a) Over Time | Baseline and Weeks 52 and 104. | 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. |
| Percent Change From Baseline in Very-Low-Density Lipoprotein (VLDL) Cholesterol | Baseline and Weeks 52 and 104. | Very-Low-Density Lipoprotein (VLDL) Cholesterol was measured in mg/dL. Samples were taken following an overnight fast. |
| Very-Low-Density Lipoprotein (VLDL) Cholesterol Over Time | Baseline and Weeks 52 and 104. | 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. |
| Percent Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol | Baseline and Weeks 52 and 104. | — |
| Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol Over Time | Baseline and Weeks 52 and 104. | 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. |
| Percent Change From Baseline in Apolipoprotein A1 | Baseline and Weeks 52 and 104. | Apolipoprotein A1 was measured in mg/dL. Samples were taken following an overnight fast. |
| Apolipoprotein A1 Over Time | Baseline and Weeks 52 and 104. | 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. |
| Percent Change From Baseline in High-Density Lipoprotein Cholesterol | Baseline and Weeks 52 and 104. | High-Density Lipoprotein (HDL) Cholesterol was measured in mg/dL. Samples were taken following an overnight fast. |
| High-Density Lipoprotein Cholesterol Over Time | Baseline and Weeks 52 and 104. | 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. |
| Triglycerides Over Time | Baseline and Weeks 52 and 104. | 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. |
| Percent Change From Baseline in Triglycerides | Baseline and Weeks 52 and 104. | Triglycerides were measured in mg/dL. Samples were taken following an overnight fast. |
Countries
United States
Participant flow
Recruitment details
Patients who completed dosing in study 301012-CS8 (NCT00280995) or 301012-CS9 (NCT00281008) at a site in the U.S. with an acceptable safety profile, per Investigator judgment, were eligible to enroll in this study.
Pre-assignment details
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). Patients who participated in study 301012-CS8 or Cohort D of study 301012-CS9 received 200 mg mipomersen QW.
Participants by arm
| Arm | Count |
|---|---|
| Mipomersen 200 mg Per Week Participants received 200 mg mipomersen once a week by subcutaneous injection, for up to 3 years. | 16 |
| Mipomersen 200 mg Every Other Week 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. | 5 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up Period | Other | 1 | 0 |
| Follow-up Period | Withdrawal by Subject | 2 | 1 |
| Year 1 and Year 2 | Adverse Event | 4 | 2 |
| Year 1 and Year 2 | Other | 1 | 0 |
| Year 1 and Year 2 | Physician Decision | 2 | 1 |
| Year 1 and Year 2 | Withdrawal by Subject | 2 | 1 |
| Year 3 | Adverse Event | 1 | 0 |
| Year 3 | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Mipomersen 200 mg Per Week | Mipomersen 200 mg Every Other Week | Total |
|---|---|---|---|
| Age, Continuous | 47.1 years STANDARD_DEVIATION 11.6 | 54.6 years STANDARD_DEVIATION 15.7 | 48.9 years STANDARD_DEVIATION 12.7 |
| Alcohol use Current | 13 participants | 3 participants | 16 participants |
| Alcohol use Never | 2 participants | 2 participants | 4 participants |
| Alcohol use Non-current | 1 participants | 0 participants | 1 participants |
| Body Mass Index (BMI) | 28.9 kg/m^2 STANDARD_DEVIATION 5.6 | 27.4 kg/m^2 STANDARD_DEVIATION 4.81 | 28.6 kg/m^2 STANDARD_DEVIATION 5.34 |
| Metabolic syndrome No | 8 participants | 3 participants | 11 participants |
| Metabolic syndrome Yes | 8 participants | 2 participants | 10 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Multiple | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 15 participants | 5 participants | 20 participants |
| Race/Ethnicity, Customized Other race | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 14 participants | 5 participants | 19 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 12 Participants | 3 Participants | 15 Participants |
| Tobacco Use Current | 1 participants | 0 participants | 1 participants |
| Tobacco Use Never | 10 participants | 3 participants | 13 participants |
| Tobacco Use Non-current | 5 participants | 2 participants | 7 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 16 | 5 / 5 |
| serious Total, serious adverse events | 4 / 16 | 3 / 5 |
Outcome results
Primary
Low-density Lipoprotein Cholesterol (LDL-C) Over Time
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.
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Low-density Lipoprotein Cholesterol (LDL-C) Over Time | Baseline [N=16, 5] | 177 mg/dL |
| Mipomersen 200 mg Per Week | Low-density Lipoprotein Cholesterol (LDL-C) Over Time | Week 52 [N=13, 4] | 145 mg/dL |
| Mipomersen 200 mg Per Week | Low-density Lipoprotein Cholesterol (LDL-C) Over Time | Week 104 [N=7, 1] | 121 mg/dL |
| Mipomersen 200 mg Per Week | Low-density Lipoprotein Cholesterol (LDL-C) Over Time | Week 104/Early Termination [N=16, 5} | 144 mg/dL |
| Mipomersen 200 mg Every Other Week | Low-density Lipoprotein Cholesterol (LDL-C) Over Time | Week 104/Early Termination [N=16, 5} | 161 mg/dL |
| Mipomersen 200 mg Every Other Week | Low-density Lipoprotein Cholesterol (LDL-C) Over Time | Baseline [N=16, 5] | 131 mg/dL |
| Mipomersen 200 mg Every Other Week | Low-density Lipoprotein Cholesterol (LDL-C) Over Time | Week 104 [N=7, 1] | 162 mg/dL |
| Mipomersen 200 mg Every Other Week | Low-density Lipoprotein Cholesterol (LDL-C) Over Time | Week 52 [N=13, 4] | 127 mg/dL |
Primary
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
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.
Time frame: Baseline and Weeks 52 and 104
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Week 52 [N=13, 4] | -16.2 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Week 104 [N=7, 1] | -32.4 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Week 104/Early Termination [N=16, 5] | -13.8 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Week 52 [N=13, 4] | -2.6 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Week 104 [N=7, 1] | 30.6 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Week 104/Early Termination [N=16, 5] | 9.5 percentage of baseline |
Secondary
Apolipoprotein B Over Time
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.
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Apolipoprotein B Over Time | Baseline [N=16, 5] | 148 mg/dL |
| Mipomersen 200 mg Per Week | Apolipoprotein B Over Time | Week 52 [N=13, 4] | 136 mg/dL |
| Mipomersen 200 mg Per Week | Apolipoprotein B Over Time | Week 104 [N=7, 1] | 110 mg/dL |
| Mipomersen 200 mg Per Week | Apolipoprotein B Over Time | Week 104/Early Termination [N=16, 5] | 132 mg/dL |
| Mipomersen 200 mg Every Other Week | Apolipoprotein B Over Time | Week 104/Early Termination [N=16, 5] | 128 mg/dL |
| Mipomersen 200 mg Every Other Week | Apolipoprotein B Over Time | Baseline [N=16, 5] | 124 mg/dL |
| Mipomersen 200 mg Every Other Week | Apolipoprotein B Over Time | Week 104 [N=7, 1] | 128 mg/dL |
| Mipomersen 200 mg Every Other Week | Apolipoprotein B Over Time | Week 52 [N=13, 4] | 110 mg/dL |
Secondary
Non-High-Density Lipoprotein Cholesterol Over Time
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.
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Non-High-Density Lipoprotein Cholesterol Over Time | Week 52 [N=13, 4] | 167 mg/dL |
| Mipomersen 200 mg Per Week | Non-High-Density Lipoprotein Cholesterol Over Time | Week 104 [N=7, 1] | 161 mg/dL |
| Mipomersen 200 mg Per Week | Non-High-Density Lipoprotein Cholesterol Over Time | Baseline [N=16, 5] | 206 mg/dL |
| Mipomersen 200 mg Per Week | Non-High-Density Lipoprotein Cholesterol Over Time | Week 104/Early Termination [N=16, 5] | 164 mg/dL |
| Mipomersen 200 mg Every Other Week | Non-High-Density Lipoprotein Cholesterol Over Time | Week 104/Early Termination [N=16, 5] | 177 mg/dL |
| Mipomersen 200 mg Every Other Week | Non-High-Density Lipoprotein Cholesterol Over Time | Week 52 [N=13, 4] | 150 mg/dL |
| Mipomersen 200 mg Every Other Week | Non-High-Density Lipoprotein Cholesterol Over Time | Baseline [N=16, 5] | 151 mg/dL |
| Mipomersen 200 mg Every Other Week | Non-High-Density Lipoprotein Cholesterol Over Time | Week 104 [N=7, 1] | 177 mg/dL |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (AEs)
AEs were considered as related if assessed by the Investigator as possibly, probably or definitely related to study drug. The severity of each event was assessed using the following categories: Mild (symptom(s) barely noticeable to the patient or do not make the patient uncomfortable); Moderate (symptom(s) of a sufficient severity to make the patient uncomfortable, performance of daily activities is influenced) or Severe (symptom(s) of a sufficient severity to cause the patient severe discomfort, may cause cessation of treatment with the study drug). Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: 2 years
Population: Safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Mild adverse event | 5 participants |
| Mipomersen 200 mg Per Week | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Severe adverse event | 3 participants |
| Mipomersen 200 mg Per Week | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Treatment-related adverse event | 16 participants |
| Mipomersen 200 mg Per Week | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Serious adverse event | 4 participants |
| Mipomersen 200 mg Per Week | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Moderate adverse event | 8 participants |
| Mipomersen 200 mg Per Week | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Adverse event leading to treatment discontinuation | 4 participants |
| Mipomersen 200 mg Per Week | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Any adverse event | 16 participants |
| Mipomersen 200 mg Every Other Week | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Adverse event leading to treatment discontinuation | 2 participants |
| Mipomersen 200 mg Every Other Week | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Any adverse event | 5 participants |
| Mipomersen 200 mg Every Other Week | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Treatment-related adverse event | 5 participants |
| Mipomersen 200 mg Every Other Week | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Mild adverse event | 2 participants |
| Mipomersen 200 mg Every Other Week | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Moderate adverse event | 3 participants |
| Mipomersen 200 mg Every Other Week | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Severe adverse event | 0 participants |
| Mipomersen 200 mg Every Other Week | Number of Participants With Treatment-Emergent Adverse Events (AEs) | Serious adverse event | 2 participants |
Secondary
Percent Change From Baseline in Apolipoprotein B
Apolipoprotein B was measured in mg/dL. Samples were taken following an overnight fast. 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.
Time frame: Baseline and Weeks 52 and 104
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Apolipoprotein B | Week 52 [N=13, 4] | -25.9 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Apolipoprotein B | Week 104 [N=7, 1] | -27.2 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Apolipoprotein B | Week 104/Early Termination [N=16, 5] | -15.8 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Apolipoprotein B | Week 52 [N=13, 4] | -7.3 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Apolipoprotein B | Week 104 [N=7, 1] | 20.8 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Apolipoprotein B | Week 104/Early Termination [N=16, 5] | -3.7 percentage of baseline |
Secondary
Percent Change From Baseline in Blood Pressure
Time frame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.
Population: Safety set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Blood Pressure | Systolic Blood Pressure | 6.99 percentage of baseline | Standard Deviation 12.33 |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Blood Pressure | Diastolic Blood Pressure | -0.88 percentage of baseline | Standard Deviation 11.31 |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Blood Pressure | Systolic Blood Pressure | 2.35 percentage of baseline | Standard Deviation 12.54 |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Blood Pressure | Diastolic Blood Pressure | 10.67 percentage of baseline | Standard Deviation 15.35 |
Secondary
Percent Change From Baseline in Clinical Chemistry Parameters
Time frame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.
Population: Safety set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Clinical Chemistry Parameters | Alanine aminotransferase (ALT) | 63.73 percentage of baseline | Standard Deviation 112.98 |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Clinical Chemistry Parameters | Aspartate aminotransferase (AST) | 48.73 percentage of baseline | Standard Deviation 86 |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Clinical Chemistry Parameters | Bilirubin, Indirect | 13.81 percentage of baseline | Standard Deviation 20.56 |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Clinical Chemistry Parameters | Bilirubin, Total | 34.79 percentage of baseline | Standard Deviation 57.97 |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Clinical Chemistry Parameters | Blood Urea Nitrogen (BUN) | 6.08 percentage of baseline | Standard Deviation 22.9 |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase | -17.24 percentage of baseline | Standard Deviation 36.85 |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Clinical Chemistry Parameters | Creatinine | -9.94 percentage of baseline | Standard Deviation 12.54 |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Clinical Chemistry Parameters | Glomerular Filtration Rate (GFR) | 16.20 percentage of baseline | Standard Deviation 24.56 |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Clinical Chemistry Parameters | Glomerular Filtration Rate (GFR) | 15.49 percentage of baseline | Standard Deviation 21.58 |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Clinical Chemistry Parameters | Alanine aminotransferase (ALT) | 29.96 percentage of baseline | Standard Deviation 80.01 |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Clinical Chemistry Parameters | Blood Urea Nitrogen (BUN) | -11.06 percentage of baseline | Standard Deviation 16.56 |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Clinical Chemistry Parameters | Aspartate aminotransferase (AST) | 3.53 percentage of baseline | Standard Deviation 39.14 |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Clinical Chemistry Parameters | Creatinine | -9.84 percentage of baseline | Standard Deviation 14.05 |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Clinical Chemistry Parameters | Bilirubin, Indirect | 12.50 percentage of baseline | Standard Deviation 29.86 |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Clinical Chemistry Parameters | Creatine Kinase | 40.95 percentage of baseline | Standard Deviation 149.95 |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Clinical Chemistry Parameters | Bilirubin, Total | 0.48 percentage of baseline | Standard Deviation 10.96 |
Secondary
Percent Change From Baseline in Hematology Parameters
Time frame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment
Population: Safety set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Hematology Parameters | Hemoglobin | 0.90 percentage of baseline | Standard Deviation 7.61 |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Hematology Parameters | Platelets | -8.55 percentage of baseline | Standard Deviation 11.88 |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Hematology Parameters | Leukocytes | -0.80 percentage of baseline | Standard Deviation 31.95 |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Hematology Parameters | Hematocrit | -0.04 percentage of baseline | Standard Deviation 8.69 |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Hematology Parameters | Leukocytes | -5.99 percentage of baseline | Standard Deviation 43.17 |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Hematology Parameters | Hemoglobin | -4.24 percentage of baseline | Standard Deviation 4.44 |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Hematology Parameters | Hematocrit | -5.24 percentage of baseline | Standard Deviation 3.69 |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Hematology Parameters | Platelets | -1.36 percentage of baseline | Standard Deviation 12.31 |
Secondary
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol
Non-high-density lipoprotein cholesterol was measured in mg/dL. Samples were taken following an overnight fast.
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol | Week 104 [N=7, 1] | -34.3 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol | Week 104/Early Termination [N=16, 5] | -16.5 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol | Week 52 [N=13, 4] | -24.7 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol | Week 52 [N=13, 4] | -6.7 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol | Week 104 [N=7, 1] | 17.2 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol | Week 104/Early Termination [N=16, 5] | 3.7 percentage of baseline |
Secondary
Percent Change From Baseline in Pulse Rate
Time frame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Pulse Rate | 4.89 percentage of baseline | Standard Deviation 14.41 |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Pulse Rate | 6.28 percentage of baseline | Standard Deviation 17.45 |
Secondary
Percent Change From Baseline in Respiratory Rate
Time frame: Baseline and Week 104 or the Early Termination visit for participants who did not complete 2 years of treatment.
Population: Safety set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Respiratory Rate | 0.87 percentage of baseline | Standard Deviation 10.57 |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Respiratory Rate | -4.44 percentage of baseline | Standard Deviation 13.3 |
Secondary
Percent Change From Baseline in Total Cholesterol
Total cholesterol was measured in mg/dL. Samples were taken following an overnight fast.
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Total Cholesterol | Week 104 [N=7, 1] | -25.3 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Total Cholesterol | Week 104/Early Termination [N=16, 5] | -11.2 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Total Cholesterol | Week 52 [N=13, 4] | -10.5 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Total Cholesterol | Week 52 [N=13, 4] | -6.5 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Total Cholesterol | Week 104 [N=7, 1] | -1.5 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Total Cholesterol | Week 104/Early Termination [N=16, 5] | -1.5 percentage of baseline |
Secondary
Total Cholesterol Over Time
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.
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Total Cholesterol Over Time | Baseline [N=16, 5] | 251 mg/dL |
| Mipomersen 200 mg Per Week | Total Cholesterol Over Time | Week 52 [N=13, 4] | 216 mg/dL |
| Mipomersen 200 mg Per Week | Total Cholesterol Over Time | Week 104 [N=7, 1] | 209 mg/dL |
| Mipomersen 200 mg Per Week | Total Cholesterol Over Time | Week 104/Early Termination [N=16, 5] | 209 mg/dL |
| Mipomersen 200 mg Every Other Week | Total Cholesterol Over Time | Week 104/Early Termination [N=16, 5] | 231 mg/dL |
| Mipomersen 200 mg Every Other Week | Total Cholesterol Over Time | Baseline [N=16, 5] | 233 mg/dL |
| Mipomersen 200 mg Every Other Week | Total Cholesterol Over Time | Week 104 [N=7, 1] | 196 mg/dL |
| Mipomersen 200 mg Every Other Week | Total Cholesterol Over Time | Week 52 [N=13, 4] | 203 mg/dL |
Other Pre-specified
Apolipoprotein A1 Over Time
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.
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Apolipoprotein A1 Over Time | Baseline [N=16, 5] | 132 mg/dL |
| Mipomersen 200 mg Per Week | Apolipoprotein A1 Over Time | Week 52 [N=13, 4] | 139 mg/dL |
| Mipomersen 200 mg Per Week | Apolipoprotein A1 Over Time | Week 104 [N=7, 1] | 142 mg/dL |
| Mipomersen 200 mg Per Week | Apolipoprotein A1 Over Time | Week 104/Early Termination [N=16, 5] | 141 mg/dL |
| Mipomersen 200 mg Every Other Week | Apolipoprotein A1 Over Time | Week 104/Early Termination [N=16, 5] | 144 mg/dL |
| Mipomersen 200 mg Every Other Week | Apolipoprotein A1 Over Time | Baseline [N=16, 5] | 149 mg/dL |
| Mipomersen 200 mg Every Other Week | Apolipoprotein A1 Over Time | Week 104 [N=7, 1] | 66 mg/dL |
| Mipomersen 200 mg Every Other Week | Apolipoprotein A1 Over Time | Week 52 [N=13, 4] | 159 mg/dL |
Other Pre-specified
High-Density Lipoprotein Cholesterol Over Time
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.
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | High-Density Lipoprotein Cholesterol Over Time | Baseline [N=16, 5] | 40 mg/dL |
| Mipomersen 200 mg Per Week | High-Density Lipoprotein Cholesterol Over Time | Week 52 [N=13, 4] | 46 mg/dL |
| Mipomersen 200 mg Per Week | High-Density Lipoprotein Cholesterol Over Time | Week 104 [N=7, 1] | 47 mg/dL |
| Mipomersen 200 mg Per Week | High-Density Lipoprotein Cholesterol Over Time | Week 104/Early Termination [N=16, 5] | 47 mg/dL |
| Mipomersen 200 mg Every Other Week | High-Density Lipoprotein Cholesterol Over Time | Week 104/Early Termination [N=16, 5] | 45 mg/dL |
| Mipomersen 200 mg Every Other Week | High-Density Lipoprotein Cholesterol Over Time | Baseline [N=16, 5] | 52 mg/dL |
| Mipomersen 200 mg Every Other Week | High-Density Lipoprotein Cholesterol Over Time | Week 104 [N=7, 1] | 19 mg/dL |
| Mipomersen 200 mg Every Other Week | High-Density Lipoprotein Cholesterol Over Time | Week 52 [N=13, 4] | 54 mg/dL |
Other Pre-specified
Lipoprotein(a) Over Time
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.
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Lipoprotein(a) Over Time | Baseline [N=16, 5] | 50 mg/dL |
| Mipomersen 200 mg Per Week | Lipoprotein(a) Over Time | Week 52 [N=13, 4] | 54 mg/dL |
| Mipomersen 200 mg Per Week | Lipoprotein(a) Over Time | Week 104 [N=7, 1] | 49 mg/dL |
| Mipomersen 200 mg Per Week | Lipoprotein(a) Over Time | Week 104/Early Termination [N=16, 5] | 47 mg/dL |
| Mipomersen 200 mg Every Other Week | Lipoprotein(a) Over Time | Week 104/Early Termination [N=16, 5] | 4 mg/dL |
| Mipomersen 200 mg Every Other Week | Lipoprotein(a) Over Time | Baseline [N=16, 5] | 5 mg/dL |
| Mipomersen 200 mg Every Other Week | Lipoprotein(a) Over Time | Week 104 [N=7, 1] | 3 mg/dL |
| Mipomersen 200 mg Every Other Week | Lipoprotein(a) Over Time | Week 52 [N=13, 4] | 4 mg/dL |
Other Pre-specified
Percent Change From Baseline in Apolipoprotein A1
Apolipoprotein A1 was measured in mg/dL. Samples were taken following an overnight fast.
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Apolipoprotein A1 | Week 104 [N=7, 1] | 5.9 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Apolipoprotein A1 | Week 104/Early Termination [N=16, 5] | 6.3 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Apolipoprotein A1 | Week 52 [N=13, 4] | 4.6 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Apolipoprotein A1 | Week 52 [N=13, 4] | 7.4 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Apolipoprotein A1 | Week 104 [N=7, 1] | -55.1 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Apolipoprotein A1 | Week 104/Early Termination [N=16, 5] | -7.9 percentage of baseline |
Other Pre-specified
Percent Change From Baseline in High-Density Lipoprotein Cholesterol
High-Density Lipoprotein (HDL) Cholesterol was measured in mg/dL. Samples were taken following an overnight fast.
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Percent Change From Baseline in High-Density Lipoprotein Cholesterol | Week 104 [N=7, 1] | 14.9 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in High-Density Lipoprotein Cholesterol | Week 104/Early Termination [N=16, 5] | 15.3 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in High-Density Lipoprotein Cholesterol | Week 52 [N=13, 4] | 12.8 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in High-Density Lipoprotein Cholesterol | Week 52 [N=13, 4] | 6.8 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in High-Density Lipoprotein Cholesterol | Week 104 [N=7, 1] | -60.4 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in High-Density Lipoprotein Cholesterol | Week 104/Early Termination [N=16, 5] | -17.9 percentage of baseline |
Other Pre-specified
Percent Change From Baseline in Lipoprotein(a)
Lipoprotein(a) was measured in mg/dL. Samples were taken following an overnight fast.
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Lipoprotein(a) | Week 52 [N=13, 4] | -20.2 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Lipoprotein(a) | Week 104 [N=7, 1] | -30.7 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Lipoprotein(a) | Week 104/Early Termination [N=16, 5] | -18.2 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Lipoprotein(a) | Week 52 [N=13, 4] | 0.0 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Lipoprotein(a) | Week 104 [N=7, 1] | 0.0 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Lipoprotein(a) | Week 104/Early Termination [N=16, 5] | -20.0 percentage of baseline |
Other Pre-specified
Percent Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol | Week 52 [N=13, 4] | -33.5 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol | Week 104 [N=7, 1] | -41.2 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol | Week 104/Early Termination [N=16, 5] | -24.9 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol | Week 52 [N=13, 4] | 2.6 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol | Week 104 [N=7, 1] | 230.1 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol | Week 104/Early Termination [N=16, 5] | 15.2 percentage of baseline |
Other Pre-specified
Percent Change From Baseline in Triglycerides
Triglycerides were measured in mg/dL. Samples were taken following an overnight fast.
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Triglycerides | Week 104 [N=7, 1] | -46.8 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Triglycerides | Week 52 [N=13, 4] | -30.2 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Triglycerides | Week 104/Early Termination [N=16, 5] | -34.3 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Triglycerides | Week 52 [N=13, 4] | -27.0 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Triglycerides | Week 104 [N=7, 1] | -44.8 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Triglycerides | Week 104/Early Termination [N=16, 5] | -34.7 percentage of baseline |
Other Pre-specified
Percent Change From Baseline in Very-Low-Density Lipoprotein (VLDL) Cholesterol
Very-Low-Density Lipoprotein (VLDL) Cholesterol was measured in mg/dL. Samples were taken following an overnight fast.
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Very-Low-Density Lipoprotein (VLDL) Cholesterol | Week 104 [N=7, 1] | -48.6 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Very-Low-Density Lipoprotein (VLDL) Cholesterol | Week 104/Early Termination [N=16, 5] | -34.0 percentage of baseline |
| Mipomersen 200 mg Per Week | Percent Change From Baseline in Very-Low-Density Lipoprotein (VLDL) Cholesterol | Week 52 [N=13, 4] | -31.6 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Very-Low-Density Lipoprotein (VLDL) Cholesterol | Week 52 [N=13, 4] | -25.9 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Very-Low-Density Lipoprotein (VLDL) Cholesterol | Week 104 [N=7, 1] | -44.4 percentage of baseline |
| Mipomersen 200 mg Every Other Week | Percent Change From Baseline in Very-Low-Density Lipoprotein (VLDL) Cholesterol | Week 104/Early Termination [N=16, 5] | -35.0 percentage of baseline |
Other Pre-specified
Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol Over Time
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.
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol Over Time | Baseline [N=16, 5] | 4 ratio |
| Mipomersen 200 mg Per Week | Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol Over Time | Week 52 [N=13, 4] | 3 ratio |
| Mipomersen 200 mg Per Week | Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol Over Time | Week 104 [N=7, 1] | 3 ratio |
| Mipomersen 200 mg Per Week | Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol Over Time | Week 104/Early Termination [N=16, 5] | 3 ratio |
| Mipomersen 200 mg Every Other Week | Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol Over Time | Week 104/Early Termination [N=16, 5] | 5 ratio |
| Mipomersen 200 mg Every Other Week | Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol Over Time | Baseline [N=16, 5] | 3 ratio |
| Mipomersen 200 mg Every Other Week | Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol Over Time | Week 104 [N=7, 1] | 9 ratio |
| Mipomersen 200 mg Every Other Week | Ratio of Low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol Over Time | Week 52 [N=13, 4] | 3 ratio |
Other Pre-specified
Triglycerides Over Time
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.
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Triglycerides Over Time | Baseline [N=16, 5] | 167 mg/dL |
| Mipomersen 200 mg Per Week | Triglycerides Over Time | Week 52 [N=13, 4] | 102 mg/dL |
| Mipomersen 200 mg Per Week | Triglycerides Over Time | Week 104 [N=7, 1] | 77 mg/dL |
| Mipomersen 200 mg Per Week | Triglycerides Over Time | Week 104/Early Termination [N=16, 5] | 98 mg/dL |
| Mipomersen 200 mg Every Other Week | Triglycerides Over Time | Week 104/Early Termination [N=16, 5] | 122 mg/dL |
| Mipomersen 200 mg Every Other Week | Triglycerides Over Time | Baseline [N=16, 5] | 134 mg/dL |
| Mipomersen 200 mg Every Other Week | Triglycerides Over Time | Week 104 [N=7, 1] | 74 mg/dL |
| Mipomersen 200 mg Every Other Week | Triglycerides Over Time | Week 52 [N=13, 4] | 90 mg/dL |
Other Pre-specified
Very-Low-Density Lipoprotein (VLDL) Cholesterol Over Time
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.
Time frame: Baseline and Weeks 52 and 104.
Population: The Safety Set included all enrolled patients who received at least 1 injection of study drug. N indicates the number of participants with available data at the specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mipomersen 200 mg Per Week | Very-Low-Density Lipoprotein (VLDL) Cholesterol Over Time | Baseline [N=16, 5] | 34 mg/dL |
| Mipomersen 200 mg Per Week | Very-Low-Density Lipoprotein (VLDL) Cholesterol Over Time | Week 52 [N=13, 4] | 20 mg/dL |
| Mipomersen 200 mg Per Week | Very-Low-Density Lipoprotein (VLDL) Cholesterol Over Time | Week 104 [N=7, 1] | 15 mg/dL |
| Mipomersen 200 mg Per Week | Very-Low-Density Lipoprotein (VLDL) Cholesterol Over Time | Week 104/Early Termination [N=16, 5] | 20 mg/dL |
| Mipomersen 200 mg Every Other Week | Very-Low-Density Lipoprotein (VLDL) Cholesterol Over Time | Week 104/Early Termination [N=16, 5] | 24 mg/dL |
| Mipomersen 200 mg Every Other Week | Very-Low-Density Lipoprotein (VLDL) Cholesterol Over Time | Baseline [N=16, 5] | 27 mg/dL |
| Mipomersen 200 mg Every Other Week | Very-Low-Density Lipoprotein (VLDL) Cholesterol Over Time | Week 104 [N=7, 1] | 15 mg/dL |
| Mipomersen 200 mg Every Other Week | Very-Low-Density Lipoprotein (VLDL) Cholesterol Over Time | Week 52 [N=13, 4] | 18 mg/dL |