Familial Chylomicronemia Syndrome
Conditions
Keywords
FCS
Brief summary
The purpose of the study was to evaluate the efficacy of olezarsen as compared to placebo on the percent change in fasting triglycerides (TG) from baseline.
Detailed description
This was a multi-center, double-blind, Phase 3 study in up to 60 patients with FCS. Participants were randomized in a 2:1 ratio to receive Olezarsen or matching placebo in a 53-week treatment period. The length of participation in the study was approximately 74 weeks, which included an up to 8-week screening period, a 53-week treatment period, and a 13-week post-treatment evaluation period. Following the treatment period, eligible patients had the option to enroll in the Open-label Extension (OLE) Study ISIS 678354-CS13 (NCT05130450).
Interventions
DRUGOlezarsen
Olezarsen was administered by SC injection.
DRUGPlacebo
Olezarsen-matching placebo was administered by SC injection.
Sponsors
Ionis Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * A diagnosis of genetically confirmed Familial Chylomicronemia Syndrome (type 1 Hyperlipoproteinemia) * Fasting TG ≥ 880 mg/dL (10 millimoles per liter (mmol/L) at Screening * History of pancreatitis. Patients without a documented history of pancreatitis are also eligible but their enrollment will be capped at 35% * Stable doses of statins, omega-3 fatty acids, fibrates, or other lipid-lowering medications are allowed Key
Exclusion criteria
* Acute coronary syndrome within 6 months of Screening * Major surgery within 3 months of Screening * Have any other conditions, which, in the opinion of the Investigator would make the participant unsuitable for inclusion, or could interfere with participating in or completing the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in Fasting TG at Month 6 | Baseline, Month 6 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Fasting TG at Month 12 | Baseline, Month 12 | — |
| Percentage of Participants With ≥ 40% Reduction in Fasting TG at Month 6 | Month 6 | Percentages are rounded off to the nearest single decimal place. |
| Percent Change From Baseline in Fasting Apolipoprotein B-48 (apoB-48) at Months 6 and 12 | Baseline, Months 6 and 12 | — |
| Percent Change From Baseline in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Months 6 and 12 | Baseline, Months 6 and 12 | — |
| Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During the Treatment Period (Week 1 Through Week 53) in Participants With Prior History of Pancreatitis | During the treatment period Week 1 through Week 53 | All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the Acute Pancreatitis Adjudication Committee (PAC) Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the treatment period. |
| Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During the Treatment Period (Week 1 Through Week 53) | During the treatment period Week 1 through Week 53 | All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the treatment period. |
| Percent Change From Baseline in Fasting Apolipoprotein C-III (apoC-III) at Months 6 and 12 | Baseline, Months 6 and 12 | — |
| Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Week 13 to Week 53 | Week 13 through Week 53 | All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the specified duration. |
| Percentage of Participants With ≥ 70% Reduction in Fasting TG at Month 6 | Month 6 | Percentages are rounded off to the nearest single decimal place. |
| Percentage of Participants With Fasting TG ≤ 880 mg/dL at Month 6 | Month 6 | Percentages are rounded off to the nearest single decimal place. |
| Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Treatment Period in Participants With ≥ 2 Events in 5 Years Prior to Enrollment | During the treatment period Week 1 through Week 53 | All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the treatment period. |
| Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years From Week 13 to Week 53 in Participants With ≥ 2 Events in 5 Years Prior to Enrollment | Week 13 to Week 53 | All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the specified duration. |
| Percentage of Participants With Fasting TG ≤ 500 mg/dL at Month 6 | Month 6 | Percentages are rounded off to the nearest single decimal place. |
| Adjudicated Acute Pancreatitis Mean Event Per 100 Participant-Years Rate During Week 13 Through Week 53 in Participants With Prior History of Pancreatitis | Week 13 through Week 53 | All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the specified duration. |
Countries
Canada, France, Italy, Netherlands, Norway, Portugal, Slovakia, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at investigative sites in the United States, Canada, France, Italy, Netherlands, Norway, Portugal, Slovakia, Spain, Sweden and the United Kingdom from 18 November 2020 to 17 October 2023.
Pre-assignment details
Participants with Familial Chylomicronemia Syndrome (FCS) were enrolled and randomized to receive either olezarsen (50 milligrams \[mg\] or 80 mg) or olezarsen-matching placebo for a 53-week treatment period. Participants completing treatment had an option to enroll in the Open-label Extension (OLE) Study ISIS 678354-CS13 (NCT05130450).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received olezarsen-matching placebo, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period. | 23 |
| Olezarsen 50 mg Participants received olezarsen 50 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period. | 21 |
| Olezarsen 80 mg Participants received olezarsen 80 mg, once every 4 weeks by SC injection, during Weeks 1 to 49 of the 53-week treatment period. | 22 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Events (AE) or Serious Adverse Events (SAE) | 0 | 1 | 2 |
| Overall Study | Investigator Judgement | 1 | 0 | 0 |
| Overall Study | Voluntary Withdrawal | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Olezarsen 50 mg | Olezarsen 80 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 44.0 years STANDARD_DEVIATION 14.67 | 43.2 years STANDARD_DEVIATION 12.11 | 47.7 years STANDARD_DEVIATION 13.3 | 45 years STANDARD_DEVIATION 13.38 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 1 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 18 Participants | 21 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fasting Triglycerides (TG) | 2595.7 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 1255.72 | 2683.8 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 1235.06 | 2613.1 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 1498.96 | 2629.5 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 1315.45 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 17 Participants | 17 Participants | 56 Participants |
| Sex: Female, Male Female | 12 Participants | 15 Participants | 11 Participants | 38 Participants |
| Sex: Female, Male Male | 11 Participants | 6 Participants | 11 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 1 / 21 | 0 / 22 |
| other Total, other adverse events | 19 / 23 | 17 / 21 | 18 / 22 |
| serious Total, serious adverse events | 9 / 23 | 4 / 21 | 3 / 22 |
Outcome results
Primary
Percent Change From Baseline in Fasting TG at Month 6
Time frame: Baseline, Month 6
Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Fasting TG at Month 6 | 11.52 percent change |
| Olezarsen 50 mg | Percent Change From Baseline in Fasting TG at Month 6 | -10.85 percent change |
| Olezarsen 80 mg | Percent Change From Baseline in Fasting TG at Month 6 | -31.99 percent change |
p-value: =0.000995% CI: [-69.085, -17.921]ANCOVA
p-value: =0.077595% CI: [-47.2, 2.463]ANCOVA
Secondary
Adjudicated Acute Pancreatitis Mean Event Per 100 Participant-Years Rate During Week 13 Through Week 53 in Participants With Prior History of Pancreatitis
All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the specified duration.
Time frame: Week 13 through Week 53
Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo. Overall number of participants analyzed is the number of participants with a history of pancreatitis within 10 years prior to screening. As prespecified in the protocol, data for this outcome measure was collected and reported in a pooled manner for olezarsen (combined Olezarsen 50 mg + Olezarsen 80 mg).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Adjudicated Acute Pancreatitis Mean Event Per 100 Participant-Years Rate During Week 13 Through Week 53 in Participants With Prior History of Pancreatitis | 57.89 events per 100 participant-years |
| Olezarsen 50 mg | Adjudicated Acute Pancreatitis Mean Event Per 100 Participant-Years Rate During Week 13 Through Week 53 in Participants With Prior History of Pancreatitis | 8.17 events per 100 participant-years |
p-value: =0.017495% CI: [0.028, 0.709]Negative Binomial Regression Model
Secondary
Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During the Treatment Period (Week 1 Through Week 53)
All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the treatment period.
Time frame: During the treatment period Week 1 through Week 53
Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo. As prespecified in the protocol, data for this outcome measure was collected and reported in a pooled manner for olezarsen (combined Olezarsen 50 mg + Olezarsen 80 mg).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During the Treatment Period (Week 1 Through Week 53) | 36.31 events per 100 participant-years |
| Olezarsen 50 mg | Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During the Treatment Period (Week 1 Through Week 53) | 4.37 events per 100 participant-years |
p-value: =0.014495% CI: [0.022, 0.656]Negative Binomial Regression Model
Secondary
Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During the Treatment Period (Week 1 Through Week 53) in Participants With Prior History of Pancreatitis
All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the Acute Pancreatitis Adjudication Committee (PAC) Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the treatment period.
Time frame: During the treatment period Week 1 through Week 53
Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo. Overall number of participants analyzed is the number of participants with a history of pancreatitis within 10 years prior to screening. As prespecified in the protocol, data for this outcome measure was collected and reported in a pooled manner for olezarsen (combined Olezarsen 50 mg + Olezarsen 80 mg)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During the Treatment Period (Week 1 Through Week 53) in Participants With Prior History of Pancreatitis | 66.22 events per 100 participant-years |
| Olezarsen 50 mg | Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During the Treatment Period (Week 1 Through Week 53) in Participants With Prior History of Pancreatitis | 6.73 events per 100 participant-years |
p-value: =0.005295% CI: [0.02, 0.506]Negative Binomial Regression Model
Secondary
Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Treatment Period in Participants With ≥ 2 Events in 5 Years Prior to Enrollment
All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the treatment period.
Time frame: During the treatment period Week 1 through Week 53
Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo. Overall number of participants analyzed is the number of participants with ≥ 2 adjudicated acute pancreatitis events in 5 years prior to enrollment. As prespecified in the protocol, data for this outcome measure was collected and reported in a pooled manner for olezarsen (combined Olezarsen 50 mg + Olezarsen 80 mg).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Treatment Period in Participants With ≥ 2 Events in 5 Years Prior to Enrollment | 118.59 events per 100 participant-years |
| Olezarsen 50 mg | Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Treatment Period in Participants With ≥ 2 Events in 5 Years Prior to Enrollment | 16.59 events per 100 participant-years |
p-value: =0.013795% CI: [0.029, 0.669]Negative Binomial Regression Model
Secondary
Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Week 13 to Week 53
All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the specified duration.
Time frame: Week 13 through Week 53
Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo. As prespecified in the protocol, data for this outcome measure was collected and reported in a pooled manner for olezarsen (combined Olezarsen 50 mg + Olezarsen 80 mg).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Week 13 to Week 53 | 33.43 events per 100 participant-years |
| Olezarsen 50 mg | Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years During Week 13 to Week 53 | 5.42 events per 100 participant-years |
p-value: =0.031495% CI: [0.031, 0.85]Negative Binomial Regression Model
Secondary
Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years From Week 13 to Week 53 in Participants With ≥ 2 Events in 5 Years Prior to Enrollment
All AEs and SAEs that consistently occurred during the study with an event of acute pancreatitis were adjudicated by a blinded, independent committee according to the Atlanta classification of acute pancreatitis as outlined in the PAC Charter. These events were categorized as 1) documented pancreatitis, 2) probable pancreatitis, 3) possible pancreatitis, 4) unable to adjudicate and 5) no diagnosis of acute pancreatitis. The adjudicated event rate represents the average number of events per 100 participant-years during the specified duration.
Time frame: Week 13 to Week 53
Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo. Overall number of participants analyzed is the number of participants with ≥ 2 adjudicated acute pancreatitis events in 5 years prior to enrollment. As prespecified in the protocol, data for this outcome measure was collected and reported in a pooled manner for olezarsen (combined Olezarsen 50 mg + Olezarsen 80 mg).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years From Week 13 to Week 53 in Participants With ≥ 2 Events in 5 Years Prior to Enrollment | 106.91 events per 100 participant-years |
| Olezarsen 50 mg | Adjudicated Acute Pancreatitis Mean Event Rate Per 100 Participant-Years From Week 13 to Week 53 in Participants With ≥ 2 Events in 5 Years Prior to Enrollment | 21.36 events per 100 participant-years |
p-value: =0.04895% CI: [0.04, 0.986]Negative Binomial Regression Model
Secondary
Percentage of Participants With ≥ 40% Reduction in Fasting TG at Month 6
Percentages are rounded off to the nearest single decimal place.
Time frame: Month 6
Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With ≥ 40% Reduction in Fasting TG at Month 6 | 4.3 percentage of participants |
| Olezarsen 50 mg | Percentage of Participants With ≥ 40% Reduction in Fasting TG at Month 6 | 33.3 percentage of participants |
| Olezarsen 80 mg | Percentage of Participants With ≥ 40% Reduction in Fasting TG at Month 6 | 40.9 percentage of participants |
Secondary
Percentage of Participants With ≥ 70% Reduction in Fasting TG at Month 6
Percentages are rounded off to the nearest single decimal place.
Time frame: Month 6
Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With ≥ 70% Reduction in Fasting TG at Month 6 | 0 percentage of participants |
| Olezarsen 50 mg | Percentage of Participants With ≥ 70% Reduction in Fasting TG at Month 6 | 4.8 percentage of participants |
| Olezarsen 80 mg | Percentage of Participants With ≥ 70% Reduction in Fasting TG at Month 6 | 9.1 percentage of participants |
Secondary
Percentage of Participants With Fasting TG ≤ 500 mg/dL at Month 6
Percentages are rounded off to the nearest single decimal place.
Time frame: Month 6
Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo. 'Overall number of participants analyzed' indicates the number of participants with data available for the analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Fasting TG ≤ 500 mg/dL at Month 6 | 0 percentage of participants |
| Olezarsen 50 mg | Percentage of Participants With Fasting TG ≤ 500 mg/dL at Month 6 | 0 percentage of participants |
| Olezarsen 80 mg | Percentage of Participants With Fasting TG ≤ 500 mg/dL at Month 6 | 13.6 percentage of participants |
Secondary
Percentage of Participants With Fasting TG ≤ 880 mg/dL at Month 6
Percentages are rounded off to the nearest single decimal place.
Time frame: Month 6
Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo. Overall number of participants analyzed indicates the number of participants with data available for analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Fasting TG ≤ 880 mg/dL at Month 6 | 0 percentage of participants |
| Olezarsen 50 mg | Percentage of Participants With Fasting TG ≤ 880 mg/dL at Month 6 | 10.0 percentage of participants |
| Olezarsen 80 mg | Percentage of Participants With Fasting TG ≤ 880 mg/dL at Month 6 | 14.3 percentage of participants |
Secondary
Percent Change From Baseline in Fasting Apolipoprotein B-48 (apoB-48) at Months 6 and 12
Time frame: Baseline, Months 6 and 12
Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting Apolipoprotein B-48 (apoB-48) at Months 6 and 12 | Month 6 | 24.50 percent change |
| Placebo | Percent Change From Baseline in Fasting Apolipoprotein B-48 (apoB-48) at Months 6 and 12 | Month 12 | -3.52 percent change |
| Olezarsen 50 mg | Percent Change From Baseline in Fasting Apolipoprotein B-48 (apoB-48) at Months 6 and 12 | Month 6 | -8.78 percent change |
| Olezarsen 50 mg | Percent Change From Baseline in Fasting Apolipoprotein B-48 (apoB-48) at Months 6 and 12 | Month 12 | -36.41 percent change |
| Olezarsen 80 mg | Percent Change From Baseline in Fasting Apolipoprotein B-48 (apoB-48) at Months 6 and 12 | Month 6 | -59.46 percent change |
| Olezarsen 80 mg | Percent Change From Baseline in Fasting Apolipoprotein B-48 (apoB-48) at Months 6 and 12 | Month 12 | -79.15 percent change |
Comparison: Percent Change From Baseline at Month 6p-value: =0.18695% CI: [-82.612, 16.041]ANCOVA
Comparison: Percent Change From Baseline at Month 6p-value: =0.001995% CI: [-136.949, -30.982]ANCOVA
Comparison: Percent Change from Baseline at Month 12p-value: =0.421995% CI: [-113.254, 47.459]ANCOVA
Comparison: Percent Change from Baseline at Month 12p-value: =0.05695% CI: [-153.195, 1.927]ANCOVA
Secondary
Percent Change From Baseline in Fasting Apolipoprotein C-III (apoC-III) at Months 6 and 12
Time frame: Baseline, Months 6 and 12
Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting Apolipoprotein C-III (apoC-III) at Months 6 and 12 | Month 6 | 7.57 percent change |
| Placebo | Percent Change From Baseline in Fasting Apolipoprotein C-III (apoC-III) at Months 6 and 12 | Month 12 | 17.08 percent change |
| Olezarsen 50 mg | Percent Change From Baseline in Fasting Apolipoprotein C-III (apoC-III) at Months 6 and 12 | Month 6 | -57.91 percent change |
| Olezarsen 50 mg | Percent Change From Baseline in Fasting Apolipoprotein C-III (apoC-III) at Months 6 and 12 | Month 12 | -59.98 percent change |
| Olezarsen 80 mg | Percent Change From Baseline in Fasting Apolipoprotein C-III (apoC-III) at Months 6 and 12 | Month 6 | -66.13 percent change |
| Olezarsen 80 mg | Percent Change From Baseline in Fasting Apolipoprotein C-III (apoC-III) at Months 6 and 12 | Month 12 | -64.20 percent change |
Comparison: Percent Change from Baseline at Month 6p-value: <0.000195% CI: [-82.634, -48.32]ANCOVA
Comparison: Percent Change from Baseline at Month 6p-value: <0.000195% CI: [-94.553, -52.837]ANCOVA
Comparison: Percent Change from Baseline at Month 12p-value: <0.000195% CI: [-98.938, -55.177]ANCOVA
Comparison: Percent Change from Baseline at Month 12p-value: <0.000195% CI: [-104.656, -57.894]ANCOVA
Secondary
Percent Change From Baseline in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Months 6 and 12
Time frame: Baseline, Months 6 and 12
Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Months 6 and 12 | Month 6 | 5.33 percent change |
| Placebo | Percent Change From Baseline in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Months 6 and 12 | Month 12 | 12.01 percent change |
| Olezarsen 50 mg | Percent Change From Baseline in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Months 6 and 12 | Month 6 | -12.35 percent change |
| Olezarsen 50 mg | Percent Change From Baseline in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Months 6 and 12 | Month 12 | -17.84 percent change |
| Olezarsen 80 mg | Percent Change From Baseline in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Months 6 and 12 | Month 6 | -18.86 percent change |
| Olezarsen 80 mg | Percent Change From Baseline in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Months 6 and 12 | Month 12 | -27.69 percent change |
Comparison: Percent Change from Baseline Month 6p-value: =0.040195% CI: [-34.571, -0.801]ANCOVA
Comparison: Percent Change from Baseline Month 6p-value: =0.003695% CI: [-40.484, -7.911]ANCOVA
Comparison: Percent Change from Baseline at Month 12p-value: =0.013495% CI: [-53.49, -6.198]ANCOVA
Comparison: Percent Change from Baseline at Month 12p-value: =0.000995% CI: [-63.108, -16.292]ANCOVA
Secondary
Percent Change From Baseline in Fasting TG at Month 12
Time frame: Baseline, Month 12
Population: FAS included all participants that were randomly assigned to treatment and received at least 1 dose of olezarsen or placebo.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Fasting TG at Month 12 | 20.89 percent change |
| Olezarsen 50 mg | Percent Change From Baseline in Fasting TG at Month 12 | -22.92 percent change |
| Olezarsen 80 mg | Percent Change From Baseline in Fasting TG at Month 12 | -38.50 percent change |
p-value: =0.004495% CI: [-73.928, -13.692]ANCOVA
p-value: =0.000295% CI: [-90.663, -28.119]ANCOVA