A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) in Adults With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease (Established or at Increased Risk for), and/or With Severe Hypertriglyceridemia

Percent Change From Baseline in Fasting TG at Month 12

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 12

Percentage of Participants Who Achieved Fasting TG <150 mg/dL (1.69 Millimoles Per Liter [mmol/L]) at Month 6 With Baseline TG <500 mg/dL (5.65 mmol/L)

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 6

Percentage of Participants Who Achieved Fasting TG <150 mg/dL (1.69 mmol/L) at Month 12 With Baseline TG <500 mg/dL (5.65 mmol/L)

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 12

Percent Change From Baseline in Fasting Apolipoprotein C-III (ApoC-III) at Month 6

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 6

Percent Change From Baseline in Fasting ApoC-III at Month 12

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 12

Percent Change From Baseline in Fasting Very Low-density Lipoprotein Cholesterol (VLDL-C) at Month 6

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 6

Percent Change From Baseline in VLDL-C at Month 12

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 12

Percent Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at Month 6

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 6

Percent Change From Baseline in Fasting Non-HDL-C at Month 12

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 12

Percent Change From Baseline in Fasting High-density Lipoprotein Cholesterol (HDL-C) at Month 6

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 6

Percent Change From Baseline in Fasting HDL-C at Month 12

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 12

Percent Change From Baseline Fasting Remnant Cholesterol (Remnant-C) at Month 6

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 6

Percent Change From Baseline in Fasting Remnant-C at Month 12

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 12

Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Month 6

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 6

Percent Change From Baseline in Fasting ApoB at Month 12

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 12

Percent Change From Baseline in Fasting Apolipoprotein A-1 (ApoA-1) at Month 6

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 6

Percent Change From Baseline in Fasting ApoA-1 at Month 12

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 12

Percent Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C) at Month 6

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 6

Percent Change From Baseline in Fasting LDL-C at Month 12

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 12

Percent Change From Baseline in Fasting Total Cholesterol (Total-C) at Month 6

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 6

Percent Change From Baseline in Fasting Total-C at Month 12

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 12

Percentage of Participants Who Achieved Fasting TG <500 mg/dL (5.65 mmol/L) With Baseline TG ≥500 mg/dL at Month 6

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 6 was defined as the average of Weeks 25 and 27. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 6

Percentage of Participants Who Achieved Fasting TG <500 mg/dL (5.65 mmol/L) With Baseline TG ≥500 mg/dL at Month 12

Baseline was defined as the average of the pre-dose measurement on Day 1 and all non-missing measurements from the qualification period. If the Day 1 pre-dose and qualification period measurements were all missing, then the last non-missing measurement from the screening period was used as baseline. Month 12 was defined as the average of Weeks 51 and 53. If 1 of the 2 assessments was missing, then the non-missing assessment was used. Missing data after the last observed value for participants in the olezarsen arms were imputed using the J2R approach.

Time frame: Baseline, Month 12

Number of Participants With Adjudicated Acute Pancreatitis Events

All adverse events (AEs) and serious adverse events (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. Number of participants with adjudicated acute pancreatitis events were reported.

Time frame: Up to 12 months

Number of Participants With Adjudicated Acute Pancreatitis Events (≥2 Events in 5 Years Prior to Enrollment)

The adjudicated acute pancreatitis event rates were compared between pooled olezarsen treatment and placebo group using a negative binomial regression model or Poisson regression model with the treatment group and natural log transformed baseline fasting TG as the factors, and number of adjudicated acute pancreatitis events in 5 years prior to enrollment as a covariate. The logarithm of time in year that each participant observed during the treatment period were used as an offset variable. Number of participants with adjudicated acute pancreatitis events with ≥2 events in 5 years prior to enrollment were reported.

Time frame: Up to 12 months