A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx... | NCT05355402

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Participants received olezarsen-matching placebo, as a single subcutaneous (SC) injection, once every 4 weeks for 53 weeks treatment period.	Drug: Placebo
Olezarsen 50 mg	Experimental	Participants received olezarsen 50 mg, as a single 0.5 milliliters (mL) SC injection, once every 4 weeks for 53 weeks treatment period.	Drug: Olezarsen
Olezarsen 80 mg	Experimental	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.	Drug: Olezarsen

Name	Type	Description	Arm Group Labels	Other Names
Olezarsen	Drug	SC injection.	Olezarsen 50 mg Olezarsen 80 mg

Measure	Description	Time Frame
Percent Change From Baseline in Fasting TG 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 jump to reference (J2R) approach.	Baseline, Month 6

Measure	Description	Time Frame
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.

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Trials Research		Lincoln	California	95648	United States
Catalina Research Institute, LLC

PubMed Identifier	Type	Citation	Retractions
38587249	Derived	Bergmark BA, Marston NA, Prohaska TA, Alexander VJ, Zimerman A, Moura FA, Murphy SA, Goodrich EL, Zhang S, Gaudet D, Karwatowska-Prokopczuk E, Tsimikas S, Giugliano RP, Sabatine MS; Bridge-TIMI 73a Investigators. Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk. N Engl J Med. 2024 May 16;390(19):1770-1780. doi: 10.1056/NEJMoa2402309. Epub 2024 Apr 7.

ID	Title	Description
FG000	Placebo	Participants received olezarsen-matching placebo, as a single subcutaneous (SC) injection, once every 4 weeks for 53 weeks treatment period.
FG001	Olezarsen 50 mg	Participants received olezarsen 50 milligrams (mg), as a single 0.5 milliliters (mL) SC injection, once every 4 weeks for 53 weeks treatment period.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Mar 22, 2023

Primary

Percent Change From Baseline in Fasting TG 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 jump to reference (J2R) approach.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

Percent Change

Baseline, Month 6

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Units	Counts
Participants	OG00039 OG00158 OG00257

Title

Denominators

Categories

Title	Measurements
	OG000-7.77(-15.34 to -0.21) OG001-57.05(-63.19 to -50.92) OG002-60.92(-67.11 to -54.73)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		<0.0001	Analysis of covariance (ANCOVA) included percent change from baseline to Month 6 in fasting TG as the dependent variable, treatment group as a fixed effect, and log-transformed baseline TG value as a covariate.	Least Squares (LS) Mean Difference	-49.28			2-Sided	95	-59.02	-39.54			Difference in the LS mean was calculated as olezarsen 50 mg - placebo.		Superiority

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 12

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo). Here, the "overall number of participants analyzed" are the number of participants with baseline TG <500 mg/dL (5.65 mmol/L).

Posted

Number

percentage of participants

Baseline, Month 6

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo). Here, the "overall number of participants analyzed" are the number of participants with baseline triglycerides <500 mg/dL (5.65 mmol/L).

Posted

Number

percentage of participants

Baseline, Month 12

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 6

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 12

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 6

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 12

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 6

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 12

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 6

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 12

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 6

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 12

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 6

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 12

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 6

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 12

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 6

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 12

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 6

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline, Month 12

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo). Here, the "overall number of participants analyzed" is the number of participants with baseline TG ≥500 mg/dL.

Posted

Number

percentage of participants

Baseline, Month 6

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo). Here, the "overall number of participants analyzed" is the number of participants with baseline TG ≥500 mg/dL.

Posted

Number

percentage of participants

Baseline, Month 12

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Count of Participants

Participants

Up to 12 months

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.

Secondary

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.

FAS included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Posted

Count of Participants

Participants

Up to 12 months

ID	Title	Description
OG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
OG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
OG002	Olezarsen 80 mg

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected58 at risk EG0020 affected57 at risk
Angina pectoris	Cardiac disorders	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected58 at risk EG0021 affected57 at risk
Atrial fibrillation	Cardiac disorders	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected58 at risk EG0020 affected57 at risk
Coronary artery disease	Cardiac disorders	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected58 at risk EG0020 affected57 at risk
Left ventricular failure	Cardiac disorders	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected58 at risk EG0020 affected57 at risk
Tachycardia	Cardiac disorders	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected58 at risk EG0021 affected57 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected58 at risk EG0020 affected57 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected58 at risk EG0021 affected57 at risk
Death	General disorders	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected58 at risk EG0020 affected57 at risk
Drug withdrawal syndrome	General disorders	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected58 at risk EG0021 affected57 at risk
Sepsis	Infections and infestations	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0011 affected58 at risk EG0021 affected57 at risk
Cellulitis	Infections and infestations	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected58 at risk EG0021 affected57 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA26.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected58 at risk EG0021 affected57 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA26.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected58 at risk EG0020 affected57 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA26.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected58 at risk EG0020 affected57 at risk
Invasive ductal breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected58 at risk EG0021 affected57 at risk
Non-Hodgkin's lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected58 at risk EG0021 affected57 at risk
Rectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected58 at risk EG0021 affected57 at risk
Squamous cell carcinoma of head and neck	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected58 at risk EG0021 affected57 at risk
Endometrial cancer stage I	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA26.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected58 at risk EG0020 affected57 at risk
Encephalopathy	Nervous system disorders	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected58 at risk EG0021 affected57 at risk
Lacunar infarction	Nervous system disorders	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0010 affected58 at risk EG0021 affected57 at risk
Syncope	Nervous system disorders	MedDRA26.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected58 at risk EG0020 affected57 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Injection site erythema	General disorders	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0018 affected58 at risk EG0022 affected57 at risk
Fatigue	General disorders	MedDRA26.0	Systematic Assessment	EG0001 affected39 at risk EG0016 affected58 at risk EG0021 affected57 at risk
COVID-19	Infections and infestations	MedDRA26.0	Systematic Assessment	EG0002 affected39 at risk EG0015 affected58 at risk EG0024 affected57 at risk
Urinary tract infection	Infections and infestations	MedDRA26.0	Systematic Assessment	EG0006 affected39 at risk EG0016 affected58 at risk EG0023 affected57 at risk
Nasopharyngitis	Infections and infestations	MedDRA26.0	Systematic Assessment	EG0002 affected39 at risk EG0012 affected58 at risk EG0023 affected57 at risk
Acute sinusitis	Infections and infestations	MedDRA26.0	Systematic Assessment	EG0001 affected39 at risk EG0011 affected58 at risk EG0023 affected57 at risk
Bronchitis	Infections and infestations	MedDRA26.0	Systematic Assessment	EG0003 affected39 at risk EG0013 affected58 at risk EG0020 affected57 at risk
Cellulitis	Infections and infestations	MedDRA26.0	Systematic Assessment	EG0002 affected39 at risk EG0011 affected58 at risk EG0021 affected57 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA26.0	Systematic Assessment	EG0002 affected39 at risk EG0011 affected58 at risk EG0020 affected57 at risk
Sinusitis	Infections and infestations	MedDRA26.0	Systematic Assessment	EG0004 affected39 at risk EG0011 affected58 at risk EG0021 affected57 at risk
Pyelonephritis	Infections and infestations	MedDRA26.0	Systematic Assessment	EG0002 affected39 at risk EG0010 affected58 at risk EG0020 affected57 at risk
Fall	Injury, poisoning and procedural complications	MedDRA26.0	Systematic Assessment	EG0002 affected39 at risk EG0010 affected58 at risk EG0021 affected57 at risk
Skin abrasion	Injury, poisoning and procedural complications	MedDRA26.0	Systematic Assessment	EG0002 affected39 at risk EG0010 affected58 at risk EG0020 affected57 at risk
Alanine aminotransferase increased	Investigations	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0013 affected58 at risk EG0023 affected57 at risk
Liver function test increased	Investigations	MedDRA26.0	Systematic Assessment	EG0000 affected39 at risk EG0013 affected58 at risk EG0021 affected57 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA26.0	Systematic Assessment	EG0001 affected39 at risk EG0010 affected58 at risk EG0023 affected57 at risk
Glomerular filtration rate decreased	Investigations	MedDRA26.0	Systematic Assessment	EG0003 affected39 at risk EG0011 affected58 at risk EG0020 affected57 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA26.0	Systematic Assessment	EG0001 affected39 at risk EG0014 affected58 at risk EG0024 affected57 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA26.0	Systematic Assessment	EG0002 affected39 at risk EG0011 affected58 at risk EG0021 affected57 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA26.0	Systematic Assessment	EG0001 affected39 at risk EG0015 affected58 at risk EG0021 affected57 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA26.0	Systematic Assessment	EG0002 affected39 at risk EG0015 affected58 at risk EG0020 affected57 at risk
Dysuria	Renal and urinary disorders	MedDRA26.0	Systematic Assessment	EG0002 affected39 at risk EG0010 affected58 at risk EG0020 affected57 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA26.0	Systematic Assessment	EG0002 affected39 at risk EG0011 affected58 at risk EG0023 affected57 at risk
Upper respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA26.0	Systematic Assessment	EG0002 affected39 at risk EG0011 affected58 at risk EG0020 affected57 at risk
Hypertension	Vascular disorders	MedDRA26.0	Systematic Assessment	EG0002 affected39 at risk EG0012 affected58 at risk EG0021 affected57 at risk

ID	Term
D015228	Hypertriglyceridemia
D050197	Atherosclerosis

ID	Term
D006949	Hyperlipidemias
D050171	Dyslipidemias
D052439	Lipid Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D001161	Arteriosclerosis
D001157	Arterial Occlusive Diseases
D014652	Vascular Diseases
D002318	Cardiovascular Diseases

ID	Title	Description
BG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
BG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
BG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.	0	39	2	39	22	39
EG001	Olezarsen 50 mg	Participants received olezarsen 50 mg, administered SC as a single 0.5 mL injection, once every 4 weeks, during Weeks 1 to 49 of the treatment period.	1	58	6	58	32	58
EG002	Olezarsen 80 mg	Participants received olezarsen 80 mg, administered SC as a single 0.8 mL injection, once every 4 weeks, during Weeks 1 to 49 of the treatment period.	0	57	8	57	24	57