Trial Outcomes & Findings for 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 (NCT NCT05355402)

NCT ID: NCT05355402

Last Updated: 2026-04-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

154 participants

Primary outcome timeframe

Baseline, Month 6

Results posted on

2026-04-23

Participant Flow

Participants took part at 28 clinical sites including 21 sites in the United States (US) and 7 sites in Canada from 01 June 2022 to 17 January 2023.

A total of 154 participants were enrolled in the study. All Participants were randomized in 1:1 ratio in two cohorts to receive either 50 mg, or 80 mg, and each cohort was further randomly assigned in a 3:1 ratio to receive olezarsen or olezarsen-matching placebo.

Participant milestones

Participant milestones
Measure
Placebo
Participants received olezarsen-matching placebo, as a single subcutaneous (SC) injection, once every 4 weeks for 53 weeks treatment period.
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.
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.
Overall Study
STARTED
39
58
57
Overall Study
COMPLETED
38
51
52
Overall Study
NOT COMPLETED
1
7
5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Total
n=154 Participants
Total of all reporting groups
Age, Continuous
63.3 years
STANDARD_DEVIATION 9.52 • n=60 Participants
62.3 years
STANDARD_DEVIATION 10.15 • n=56 Participants
60.4 years
STANDARD_DEVIATION 10.77 • n=116 Participants
61.8 years
STANDARD_DEVIATION 10.24 • n=7 Participants
Sex: Female, Male
Female
24 Participants
n=60 Participants
24 Participants
n=56 Participants
17 Participants
n=116 Participants
65 Participants
n=7 Participants
Sex: Female, Male
Male
15 Participants
n=60 Participants
34 Participants
n=56 Participants
40 Participants
n=116 Participants
89 Participants
n=7 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=60 Participants
0 Participants
n=56 Participants
0 Participants
n=116 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
Asian
0 Participants
n=60 Participants
1 Participants
n=56 Participants
0 Participants
n=116 Participants
1 Participants
n=7 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=60 Participants
0 Participants
n=56 Participants
0 Participants
n=116 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
Black or African American
5 Participants
n=60 Participants
3 Participants
n=56 Participants
5 Participants
n=116 Participants
13 Participants
n=7 Participants
Race (NIH/OMB)
White
34 Participants
n=60 Participants
54 Participants
n=56 Participants
52 Participants
n=116 Participants
140 Participants
n=7 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=60 Participants
0 Participants
n=56 Participants
0 Participants
n=116 Participants
0 Participants
n=7 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=60 Participants
0 Participants
n=56 Participants
0 Participants
n=116 Participants
0 Participants
n=7 Participants
Fasting Triglycerides (TG)
302.1 milligrams/deciliter (mg/dL)
STANDARD_DEVIATION 201.91 • n=60 Participants
292.1 milligrams/deciliter (mg/dL)
STANDARD_DEVIATION 183.01 • n=56 Participants
315.1 milligrams/deciliter (mg/dL)
STANDARD_DEVIATION 221.63 • n=116 Participants
303.2 milligrams/deciliter (mg/dL)
STANDARD_DEVIATION 201.7 • n=7 Participants

PRIMARY outcome

Timeframe: Baseline, Month 6

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting TG at Month 6
-7.77 Percent Change
Interval -15.34 to -0.21
-57.05 Percent Change
Interval -63.19 to -50.92
-60.92 Percent Change
Interval -67.11 to -54.73

SECONDARY outcome

Timeframe: Baseline, Month 12

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting TG at Month 12
-5.59 percent change
Interval -13.09 to 1.9
-51.67 percent change
Interval -57.74 to -45.6
-60.39 percent change
Interval -66.51 to -54.27

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: 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).

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.

Outcome measures

Outcome measures
Measure
Placebo
n=35 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=53 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=50 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
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)
11.4 percentage of participants
79.2 percentage of participants
84.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: 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).

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.

Outcome measures

Outcome measures
Measure
Placebo
n=35 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=53 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=50 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
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)
5.7 percentage of participants
69.8 percentage of participants
82.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 6

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting Apolipoprotein C-III (ApoC-III) at Month 6
-5.47 percent change
Interval -16.46 to 5.51
-69.63 percent change
Interval -79.56 to -59.71
-78.72 percent change
Interval -87.79 to -69.65

SECONDARY outcome

Timeframe: Baseline, Month 12

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting ApoC-III at Month 12
-12.40 percent change
Interval -24.02 to -0.77
-69.09 percent change
Interval -79.42 to -58.76
-83.78 percent change
Interval -93.22 to -74.34

SECONDARY outcome

Timeframe: Baseline, Month 6

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting Very Low-density Lipoprotein Cholesterol (VLDL-C) at Month 6
-9.74 percent change
Interval -20.65 to 1.17
-55.93 percent change
Interval -65.65 to -46.22
-59.46 percent change
Interval -68.79 to -50.13

SECONDARY outcome

Timeframe: Baseline, Month 12

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in VLDL-C at Month 12
-14.90 percent change
Interval -23.97 to -5.82
-58.00 percent change
Interval -66.11 to -49.88
-66.67 percent change
Interval -74.47 to -58.87

SECONDARY outcome

Timeframe: Baseline, Month 6

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at Month 6
3.28 percent change
Interval -7.04 to 13.61
-22.11 percent change
Interval -31.33 to -12.89
-19.79 percent change
Interval -28.72 to -10.85

SECONDARY outcome

Timeframe: Baseline, Month 12

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting Non-HDL-C at Month 12
-2.55 percent change
Interval -11.91 to 6.81
-20.00 percent change
Interval -28.23 to -11.76
-26.57 percent change
Interval -34.59 to -18.55

SECONDARY outcome

Timeframe: Baseline, Month 6

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting High-density Lipoprotein Cholesterol (HDL-C) at Month 6
8.38 percent change
Interval -3.7 to 20.46
48.02 percent change
Interval 37.0 to 59.04
48.01 percent change
Interval 37.18 to 58.83

SECONDARY outcome

Timeframe: Baseline, Month 12

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting HDL-C at Month 12
10.53 percent change
Interval -1.87 to 22.94
54.20 percent change
Interval 42.94 to 65.47
57.43 percent change
Interval 46.32 to 68.53

SECONDARY outcome

Timeframe: Baseline, Month 6

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline Fasting Remnant Cholesterol (Remnant-C) at Month 6
-9.46 percent change
Interval -20.39 to 1.47
-55.98 percent change
Interval -65.73 to -46.23
-59.59 percent change
Interval -68.96 to -50.22

SECONDARY outcome

Timeframe: Baseline, Month 12

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting Remnant-C at Month 12
-14.83 percent change
Interval -23.85 to -5.82
-58.17 percent change
Interval -66.2 to -50.13
-66.90 percent change
Interval -74.63 to -59.17

SECONDARY outcome

Timeframe: Baseline, Month 6

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Month 6
6.82 percent change
Interval -1.44 to 15.07
-11.42 percent change
Interval -18.8 to -4.03
-11.67 percent change
Interval -18.8 to -4.53

SECONDARY outcome

Timeframe: Baseline, Month 12

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting ApoB at Month 12
0.68 percent change
Interval -7.09 to 8.44
-11.67 percent change
Interval -18.45 to -4.9
-18.53 percent change
Interval -25.12 to -11.93

SECONDARY outcome

Timeframe: Baseline, Month 6

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting Apolipoprotein A-1 (ApoA-1) at Month 6
2.84 percent change
Interval -2.19 to 7.87
17.37 percent change
Interval 12.82 to 21.93
14.91 percent change
Interval 10.49 to 19.32

SECONDARY outcome

Timeframe: Baseline, Month 12

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting ApoA-1 at Month 12
0.81 percent change
Interval -4.11 to 5.72
16.37 percent change
Interval 11.97 to 20.78
15.46 percent change
Interval 11.15 to 19.76

SECONDARY outcome

Timeframe: Baseline, Month 6

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C) at Month 6
40.46 percent change
Interval 25.11 to 55.8
30.61 percent change
Interval 16.44 to 44.77
32.74 percent change
Interval 19.35 to 46.14

SECONDARY outcome

Timeframe: Baseline, Month 12

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting LDL-C at Month 12
35.08 percent change
Interval 21.09 to 49.08
32.99 percent change
Interval 20.52 to 45.46
27.27 percent change
Interval 15.28 to 39.26

SECONDARY outcome

Timeframe: Baseline, Month 6

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting Total Cholesterol (Total-C) at Month 6
2.99 percent change
Interval -4.94 to 10.92
-6.78 percent change
Interval -13.86 to 0.3
-6.48 percent change
Interval -13.31 to 0.35

SECONDARY outcome

Timeframe: Baseline, Month 12

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percent Change From Baseline in Fasting Total-C at Month 12
-2.15 percent change
Interval -9.25 to 4.95
-6.08 percent change
Interval -12.35 to 0.18
-10.80 percent change
Interval -16.87 to -4.72

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=4 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=5 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=7 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percentage of Participants Who Achieved Fasting TG <500 mg/dL (5.65 mmol/L) With Baseline TG ≥500 mg/dL at Month 6
75.0 percentage of participants
80.0 percentage of participants
100.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=4 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=5 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=7 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Percentage of Participants Who Achieved Fasting TG <500 mg/dL (5.65 mmol/L) With Baseline TG ≥500 mg/dL at Month 12
75.0 percentage of participants
100.0 percentage of participants
100.0 percentage of participants

SECONDARY outcome

Timeframe: Up to 12 months

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Number of Participants With Adjudicated Acute Pancreatitis Events
0 Participants
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Up to 12 months

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

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.

Outcome measures

Outcome measures
Measure
Placebo
n=39 Participants
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 Participants
Participants received olezarsen 50 mg, as a single 0.5 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 80 mg
n=57 Participants
Participants received olezarsen 80 mg, as a single 0.8 mL SC injection, once every 4 weeks for 53 weeks treatment period.
Number of Participants With Adjudicated Acute Pancreatitis Events (≥2 Events in 5 Years Prior to Enrollment)
0 Participants
0 Participants
0 Participants

Adverse Events

Placebo

Serious events: 2 serious events
Other events: 22 other events
Deaths: 0 deaths

Olezarsen 50 mg

Serious events: 6 serious events
Other events: 32 other events
Deaths: 1 deaths

Olezarsen 80 mg

Serious events: 8 serious events
Other events: 24 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Placebo
n=39 participants at risk
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 participants at risk
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.
Olezarsen 80 mg
n=57 participants at risk
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.
Cardiac disorders
Acute myocardial infarction
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.7%
1/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Cardiac disorders
Angina pectoris
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of head and neck
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer stage I
2.6%
1/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Nervous system disorders
Encephalopathy
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Nervous system disorders
Lacunar infarction
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Nervous system disorders
Syncope
2.6%
1/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Cardiac disorders
Atrial fibrillation
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.7%
1/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Cardiac disorders
Coronary artery disease
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.7%
1/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Cardiac disorders
Left ventricular failure
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.7%
1/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Cardiac disorders
Tachycardia
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Gastrointestinal disorders
Pancreatitis acute
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.7%
1/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Gastrointestinal disorders
Small intestinal obstruction
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
General disorders
Death
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.7%
1/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
General disorders
Drug withdrawal syndrome
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Infections and infestations
Sepsis
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.7%
1/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Infections and infestations
Cellulitis
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Injury, poisoning and procedural complications
Tibia fracture
2.6%
1/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Injury, poisoning and procedural complications
Head injury
2.6%
1/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Injury, poisoning and procedural complications
Ligament sprain
2.6%
1/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive ductal breast carcinoma
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-Hodgkin's lymphoma
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Other adverse events

Other adverse events
Measure
Placebo
n=39 participants at risk
Participants received olezarsen-matching placebo, as a single SC injection, once every 4 weeks for 53 weeks treatment period.
Olezarsen 50 mg
n=58 participants at risk
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.
Olezarsen 80 mg
n=57 participants at risk
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.
Infections and infestations
Cellulitis
5.1%
2/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.7%
1/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Infections and infestations
Upper respiratory tract infection
5.1%
2/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.7%
1/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Infections and infestations
Sinusitis
10.3%
4/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.7%
1/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Infections and infestations
Nasopharyngitis
5.1%
2/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
3.4%
2/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
5.3%
3/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Infections and infestations
Acute sinusitis
2.6%
1/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.7%
1/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
5.3%
3/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Infections and infestations
Bronchitis
7.7%
3/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
5.2%
3/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Investigations
Blood creatine phosphokinase increased
2.6%
1/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
5.3%
3/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Investigations
Glomerular filtration rate decreased
7.7%
3/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.7%
1/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Metabolism and nutrition disorders
Diabetes mellitus
2.6%
1/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
6.9%
4/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
7.0%
4/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Metabolism and nutrition disorders
Type 2 diabetes mellitus
5.1%
2/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.7%
1/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Musculoskeletal and connective tissue disorders
Back pain
2.6%
1/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
8.6%
5/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Musculoskeletal and connective tissue disorders
Arthralgia
5.1%
2/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
8.6%
5/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Renal and urinary disorders
Dysuria
5.1%
2/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Respiratory, thoracic and mediastinal disorders
Cough
5.1%
2/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.7%
1/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
5.3%
3/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract congestion
5.1%
2/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.7%
1/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Vascular disorders
Hypertension
5.1%
2/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
3.4%
2/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Infections and infestations
Pyelonephritis
5.1%
2/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Injury, poisoning and procedural complications
Fall
5.1%
2/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Injury, poisoning and procedural complications
Skin abrasion
5.1%
2/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
0.00%
0/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Investigations
Alanine aminotransferase increased
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
5.2%
3/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
5.3%
3/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Investigations
Liver function test increased
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
5.2%
3/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
General disorders
Injection site erythema
0.00%
0/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
13.8%
8/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
3.5%
2/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
General disorders
Fatigue
2.6%
1/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
10.3%
6/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
1.8%
1/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Infections and infestations
COVID-19
5.1%
2/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
8.6%
5/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
7.0%
4/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
Infections and infestations
Urinary tract infection
15.4%
6/39 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
10.3%
6/58 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).
5.3%
3/57 • Up to 15 months
The safety set included all participants who were randomized and received any amount of study drug (olezarsen or placebo).

Additional Information

Ionis Pharmaceuticals, Inc.

Ionis Pharmaceuticals, Inc.

Phone: 760-603-2346

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place