Trial Outcomes & Findings for Study to Evaluate ARO-APOC3 in Adults With Severe Hypertriglyceridemia (NCT NCT04720534)

NCT ID: NCT04720534

Last Updated: 2026-03-24

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

229 participants

Primary outcome timeframe

Baseline, Week 24

Results posted on

2026-03-24

Participant Flow

There were 76 study centers in 8 countries (Australia, Canada, Germany, Hungary, The Netherlands, New Zealand, Poland, and the United States \[US\]).

Participants who met all the protocol eligibility criteria during Screening were enrolled and randomly assigned to treatment in a double-blind fashion. Participants were randomly assigned 3:1 to receive 1 of 3 ARO-APOC3 dosing regimens (ARO-APOC3 10 mg, 25 mg, or 50 mg) or matched placebo.

Participant milestones

Participant milestones
Measure	Placebo, Day 1 and Week 12 Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 10 mg Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.
Overall Study STARTED	62	55	55	57
Overall Study COMPLETED	58	50	52	53
Overall Study NOT COMPLETED	4	5	3	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo, Day 1 and Week 12 Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 10 mg Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.
Overall Study Withdrawal by Subject	3	1	1	1
Overall Study Physician Decision	0	0	0	1
Overall Study Other, Not Specified	0	2	0	1
Overall Study Adverse Event	0	1	0	1
Overall Study Lost to Follow-up	1	1	2	0

Baseline Characteristics

Study to Evaluate ARO-APOC3 in Adults With Severe Hypertriglyceridemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo, Day 1 and Week 12 n=62 Participants Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 10 mg n=55 Participants Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg n=55 Participants Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg n=57 Participants Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	Total n=229 Participants Total of all reporting groups
Age, Continuous	55.8 years STANDARD_DEVIATION 11.22 • n=138 Participants	52.9 years STANDARD_DEVIATION 9.55 • n=62 Participants	56.0 years STANDARD_DEVIATION 10.64 • n=123 Participants	54.3 years STANDARD_DEVIATION 11.00 • n=158 Participants	54.9 years STANDARD_DEVIATION 10.59 • n=3208 Participants
Sex: Female, Male Female	15 Participants n=138 Participants	8 Participants n=62 Participants	12 Participants n=123 Participants	16 Participants n=158 Participants	51 Participants n=3208 Participants
Sex: Female, Male Male	47 Participants n=138 Participants	47 Participants n=62 Participants	43 Participants n=123 Participants	41 Participants n=158 Participants	178 Participants n=3208 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=138 Participants	7 Participants n=62 Participants	7 Participants n=123 Participants	6 Participants n=158 Participants	33 Participants n=3208 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	48 Participants n=138 Participants	47 Participants n=62 Participants	48 Participants n=123 Participants	51 Participants n=158 Participants	194 Participants n=3208 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=138 Participants	1 Participants n=62 Participants	0 Participants n=123 Participants	0 Participants n=158 Participants	2 Participants n=3208 Participants
Race/Ethnicity, Customized White	56 Participants n=138 Participants	48 Participants n=62 Participants	48 Participants n=123 Participants	53 Participants n=158 Participants	205 Participants n=3208 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=138 Participants	2 Participants n=62 Participants	3 Participants n=123 Participants	1 Participants n=158 Participants	7 Participants n=3208 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=138 Participants	0 Participants n=62 Participants	0 Participants n=123 Participants	0 Participants n=158 Participants	1 Participants n=3208 Participants
Race/Ethnicity, Customized Asian	3 Participants n=138 Participants	1 Participants n=62 Participants	2 Participants n=123 Participants	3 Participants n=158 Participants	9 Participants n=3208 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=138 Participants	0 Participants n=62 Participants	2 Participants n=123 Participants	0 Participants n=158 Participants	2 Participants n=3208 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=138 Participants	1 Participants n=62 Participants	0 Participants n=123 Participants	0 Participants n=158 Participants	1 Participants n=3208 Participants
Race/Ethnicity, Customized Other, Not Specified	1 Participants n=138 Participants	3 Participants n=62 Participants	0 Participants n=123 Participants	0 Participants n=158 Participants	4 Participants n=3208 Participants

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). Observed cases.

Outcome measures

Outcome measures
Measure	ARO-APOC3 10 mg n=50 Participants Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg n=54 Participants Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg n=55 Participants Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	Placebo, Day 1 and Week 12 n=59 Participants Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
Percent Change From Baseline at Week 24 in Fasting Triglycerides (TG)	-66.0 percentage change Standard Error 5.61	-70.2 percentage change Standard Error 5.51	-74.2 percentage change Standard Error 5.44	-17.2 percentage change Standard Error 5.27

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)

Population: Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). Observed cases at given time point.

Outcome measures

Outcome measures
Measure	ARO-APOC3 10 mg n=54 Participants Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg n=55 Participants Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg n=57 Participants Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	Placebo, Day 1 and Week 12 n=60 Participants Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
Percent Change From Baseline Over Time Through Week 48 in Fasting TG Week 20	-67.7 percentage change Standard Error 7.07	-75.3 percentage change Standard Error 7.02	-75.6 percentage change Standard Error 6.91	2.4 percentage change Standard Error 6.66
Percent Change From Baseline Over Time Through Week 48 in Fasting TG Week 24	-66.0 percentage change Standard Error 5.61	-70.2 percentage change Standard Error 5.51	-74.2 percentage change Standard Error 5.44	-17.2 percentage change Standard Error 5.27
Percent Change From Baseline Over Time Through Week 48 in Fasting TG Week 28	-60.0 percentage change Standard Error 6.33	-70.3 percentage change Standard Error 6.23	-70.8 percentage change Standard Error 6.11	-11.7 percentage change Standard Error 5.83
Percent Change From Baseline Over Time Through Week 48 in Fasting TG Week 36	-37.7 percentage change Standard Error 9.70	-64.0 percentage change Standard Error 9.54	-53.6 percentage change Standard Error 9.35	-7.6 percentage change Standard Error 9.08
Percent Change From Baseline Over Time Through Week 48 in Fasting TG Week 48	-31.4 percentage change Standard Error 8.20	-58.0 percentage change Standard Error 8.15	-53.4 percentage change Standard Error 7.97	-6.6 percentage change Standard Error 7.71
Percent Change From Baseline Over Time Through Week 48 in Fasting TG Week 4	-63.3 percentage change Standard Error 4.88	-79.5 percentage change Standard Error 4.81	-77.6 percentage change Standard Error 4.72	7.2 percentage change Standard Error 4.61
Percent Change From Baseline Over Time Through Week 48 in Fasting TG Week 8	-54.0 percentage change Standard Error 5.46	-73.2 percentage change Standard Error 5.45	-72.8 percentage change Standard Error 5.34	-0.7 percentage change Standard Error 5.19
Percent Change From Baseline Over Time Through Week 48 in Fasting TG Week 12	-53.9 percentage change Standard Error 7.35	-64.9 percentage change Standard Error 7.29	-70.3 percentage change Standard Error 7.24	-7.3 percentage change Standard Error 7.05
Percent Change From Baseline Over Time Through Week 48 in Fasting TG Week 16	-70.5 percentage change Standard Error 6.32	-80.1 percentage change Standard Error 6.17	-76.3 percentage change Standard Error 6.15	-2.9 percentage change Standard Error 5.91

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). Observed cases.

Outcome measures

Outcome measures
Measure	ARO-APOC3 10 mg n=49 Participants Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg n=54 Participants Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg n=55 Participants Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	Placebo, Day 1 and Week 12 n=59 Participants Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
Percent Change From Baseline at Week 24 in Apolipoprotein (Apo)C-III	-69.6 percentage change Standard Error 76.90	-73.7 percentage change Standard Error 76.04	-79.4 percentage change Standard Error 73.19	114.2 percentage change Standard Error 73.08

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)

Population: Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). Observed cases at given time point.

Outcome measures

Outcome measures
Measure	ARO-APOC3 10 mg n=54 Participants Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg n=55 Participants Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg n=57 Participants Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	Placebo, Day 1 and Week 12 n=60 Participants Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
Percent Change From Baseline Over Time Through Week 48 in ApoC-III Week 4	-67.3 percentage change Standard Error 76.79	-84.4 percentage change Standard Error 76.00	-84.6 percentage change Standard Error 73.12	209.3 percentage change Standard Error 73.06
Percent Change From Baseline Over Time Through Week 48 in ApoC-III Week 8	-59.8 percentage change Standard Error 76.76	-78.8 percentage change Standard Error 76.03	-79.9 percentage change Standard Error 73.14	146.3 percentage change Standard Error 73.06
Percent Change From Baseline Over Time Through Week 48 in ApoC-III Week 12	-55.5 percentage change Standard Error 76.79	-71.8 percentage change Standard Error 76.04	-73.2 percentage change Standard Error 73.21	122.2 percentage change Standard Error 73.13
Percent Change From Baseline Over Time Through Week 48 in ApoC-III Week 16	-77.1 percentage change Standard Error 76.90	-86.4 percentage change Standard Error 76.04	-87.1 percentage change Standard Error 73.25	134.4 percentage change Standard Error 73.09
Percent Change From Baseline Over Time Through Week 48 in ApoC-III Week 20	-71.7 percentage change Standard Error 76.87	-81.2 percentage change Standard Error 76.13	-84.0 percentage change Standard Error 73.26	118.8 percentage change Standard Error 73.11
Percent Change From Baseline Over Time Through Week 48 in ApoC-III Week 24	-69.6 percentage change Standard Error 76.90	-73.7 percentage change Standard Error 76.04	-79.4 percentage change Standard Error 73.19	114.2 percentage change Standard Error 73.08
Percent Change From Baseline Over Time Through Week 48 in ApoC-III Week 28	-64.4 percentage change Standard Error 76.89	-71.9 percentage change Standard Error 76.09	-74.7 percentage change Standard Error 73.21	140.2 percentage change Standard Error 73.06
Percent Change From Baseline Over Time Through Week 48 in ApoC-III Week 36	-50.2 percentage change Standard Error 76.92	-60.9 percentage change Standard Error 76.12	-59.9 percentage change Standard Error 73.21	152.0 percentage change Standard Error 73.13
Percent Change From Baseline Over Time Through Week 48 in ApoC-III Week 48	-34.5 percentage change Standard Error 76.89	-49.6 percentage change Standard Error 76.16	-48.3 percentage change Standard Error 73.25	135.8 percentage change Standard Error 73.14

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). Observed cases.

Outcome measures

Outcome measures
Measure	ARO-APOC3 10 mg n=49 Participants Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg n=54 Participants Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg n=55 Participants Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	Placebo, Day 1 and Week 12 n=59 Participants Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
Percent Change From Baseline at Week 24 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C)	-29.4 percentage change Standard Error 4.04	-28.4 percentage change Standard Error 3.90	-21.7 percentage change Standard Error 3.83	-1.5 percentage change Standard Error 3.76

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)

Population: Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). Observed cases at given time point.

Outcome measures

Outcome measures
Measure	ARO-APOC3 10 mg n=54 Participants Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg n=55 Participants Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg n=57 Participants Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	Placebo, Day 1 and Week 12 n=60 Participants Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
Percent Change From Baseline Over Time Through Week 48 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) Week 4	-27.0 percentage change Standard Error 3.57	-34.7 percentage change Standard Error 3.46	-26.1 percentage change Standard Error 3.37	6.3 percentage change Standard Error 3.35
Percent Change From Baseline Over Time Through Week 48 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) Week 8	-19.7 percentage change Standard Error 4.00	-30.7 percentage change Standard Error 3.92	-20.7 percentage change Standard Error 3.82	4.5 percentage change Standard Error 3.77
Percent Change From Baseline Over Time Through Week 48 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) Week 12	-19.3 percentage change Standard Error 4.77	-30.0 percentage change Standard Error 4.67	-22.3 percentage change Standard Error 4.61	1.4 percentage change Standard Error 4.54
Percent Change From Baseline Over Time Through Week 48 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) Week 16	-27.9 percentage change Standard Error 4.00	-37.8 percentage change Standard Error 3.87	-23.7 percentage change Standard Error 3.81	1.8 percentage change Standard Error 3.73
Percent Change From Baseline Over Time Through Week 48 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) Week 20	-26.7 percentage change Standard Error 4.22	-34.6 percentage change Standard Error 4.13	-22.9 percentage change Standard Error 4.04	5.7 percentage change Standard Error 3.96
Percent Change From Baseline Over Time Through Week 48 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) Week 24	-29.4 percentage change Standard Error 4.04	-28.4 percentage change Standard Error 3.90	-21.7 percentage change Standard Error 3.83	-1.5 percentage change Standard Error 3.76
Percent Change From Baseline Over Time Through Week 48 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) Week 28	-27.4 percentage change Standard Error 4.14	-31.3 percentage change Standard Error 4.02	-24.0 percentage change Standard Error 3.92	-2.3 percentage change Standard Error 3.82
Percent Change From Baseline Over Time Through Week 48 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) Week 36	-19.2 percentage change Standard Error 4.91	-23.8 percentage change Standard Error 4.78	-13.1 percentage change Standard Error 4.65	-0.3 percentage change Standard Error 4.57
Percent Change From Baseline Over Time Through Week 48 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) Week 48	-10.0 percentage change Standard Error 4.92	-23.0 percentage change Standard Error 4.83	-13.5 percentage change Standard Error 4.69	0.5 percentage change Standard Error 4.58

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). Observed cases.

Outcome measures

Outcome measures
Measure	ARO-APOC3 10 mg n=49 Participants Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg n=54 Participants Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg n=55 Participants Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	Placebo, Day 1 and Week 12 n=59 Participants Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
Percent Change From Baseline at Week 24 in Fasting High-Density Lipoprotein Cholesterol (HDL-C)	54.2 percentage change Standard Error 6.32	62.8 percentage change Standard Error 6.09	67.6 percentage change Standard Error 6.00	10.6 percentage change Standard Error 5.87

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)

Population: Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). Participants with an assessment at given time point.

Outcome measures

Outcome measures
Measure	ARO-APOC3 10 mg n=54 Participants Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg n=55 Participants Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg n=57 Participants Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	Placebo, Day 1 and Week 12 n=60 Participants Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
Percent Change From Baseline Over Time Through Week 48 in Fasting HDL-C Week 8	45.4 percentage change Standard Error 5.79	73.5 percentage change Standard Error 5.66	67.7 percentage change Standard Error 5.54	6.2 percentage change Standard Error 5.45
Percent Change From Baseline Over Time Through Week 48 in Fasting HDL-C Week 12	39.9 percentage change Standard Error 5.81	60.2 percentage change Standard Error 5.66	62.5 percentage change Standard Error 5.59	11.3 percentage change Standard Error 5.50
Percent Change From Baseline Over Time Through Week 48 in Fasting HDL-C Week 16	66.2 percentage change Standard Error 6.23	87.1 percentage change Standard Error 5.99	82.6 percentage change Standard Error 5.94	5.7 percentage change Standard Error 5.78
Percent Change From Baseline Over Time Through Week 48 in Fasting HDL-C Week 20	61.2 percentage change Standard Error 6.63	78.7 percentage change Standard Error 6.48	81.2 percentage change Standard Error 6.36	8.8 percentage change Standard Error 6.20
Percent Change From Baseline Over Time Through Week 48 in Fasting HDL-C Week 24	54.2 percentage change Standard Error 6.32	62.8 percentage change Standard Error 6.09	67.6 percentage change Standard Error 6.00	10.6 percentage change Standard Error 5.87
Percent Change From Baseline Over Time Through Week 48 in Fasting HDL-C Week 28	48.2 percentage change Standard Error 6.00	67.2 percentage change Standard Error 5.81	68.0 percentage change Standard Error 5.70	10.2 percentage change Standard Error 5.55
Percent Change From Baseline Over Time Through Week 48 in Fasting HDL-C Week 36	34.5 percentage change Standard Error 6.29	51.1 percentage change Standard Error 6.09	47.2 percentage change Standard Error 5.95	11.7 percentage change Standard Error 5.83
Percent Change From Baseline Over Time Through Week 48 in Fasting HDL-C Week 48	23.5 percentage change Standard Error 5.80	32.4 percentage change Standard Error 5.65	37.8 percentage change Standard Error 5.51	6.1 percentage change Standard Error 5.40
Percent Change From Baseline Over Time Through Week 48 in Fasting HDL-C Week 4	53.4 percentage change Standard Error 5.86	76.2 percentage change Standard Error 5.67	88.1 percentage change Standard Error 5.56	4.3 percentage change Standard Error 5.48

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). Participants with an assessment at given time point.

Outcome measures

Outcome measures
Measure	ARO-APOC3 10 mg n=49 Participants Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg n=54 Participants Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg n=55 Participants Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	Placebo, Day 1 and Week 12 n=59 Participants Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
Percent Change From Baseline at Week 24 in Fasting Total Apolipoprotein B (ApoB)	6.0 percentage change Standard Error 6.31	-5.3 percentage change Standard Error 6.06	0.7 percentage change Standard Error 6.01	8.0 percentage change Standard Error 5.85

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)

Population: Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). Participants with an assessment at given time point.

Outcome measures

Outcome measures
Measure	ARO-APOC3 10 mg n=54 Participants Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg n=55 Participants Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg n=57 Participants Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	Placebo, Day 1 and Week 12 n=60 Participants Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
Percent Change From Baseline Over Time Through Week 48 in Fasting Total ApoB Week 24	6.0 percentage change Standard Error 6.31	-5.3 percentage change Standard Error 6.06	0.7 percentage change Standard Error 6.01	8.0 percentage change Standard Error 5.85
Percent Change From Baseline Over Time Through Week 48 in Fasting Total ApoB Week 28	-1.3 percentage change Standard Error 3.92	-6.0 percentage change Standard Error 3.83	0.6 percentage change Standard Error 3.79	3.9 percentage change Standard Error 3.70
Percent Change From Baseline Over Time Through Week 48 in Fasting Total ApoB Week 36	-0.4 percentage change Standard Error 4.35	2.5 percentage change Standard Error 4.24	8.5 percentage change Standard Error 4.17	8.9 percentage change Standard Error 4.10
Percent Change From Baseline Over Time Through Week 48 in Fasting Total ApoB Week 48	6.4 percentage change Standard Error 4.28	-0.2 percentage change Standard Error 4.21	2.4 percentage change Standard Error 4.14	5.7 percentage change Standard Error 4.06
Percent Change From Baseline Over Time Through Week 48 in Fasting Total ApoB Week 4	-2.3 percentage change Standard Error 7.10	-9.0 percentage change Standard Error 6.95	-1.9 percentage change Standard Error 6.84	16.2 percentage change Standard Error 6.70
Percent Change From Baseline Over Time Through Week 48 in Fasting Total ApoB Week 8	-0.8 percentage change Standard Error 4.97	-7.2 percentage change Standard Error 4.89	1.5 percentage change Standard Error 4.82	16.0 percentage change Standard Error 4.74
Percent Change From Baseline Over Time Through Week 48 in Fasting Total ApoB Week 16	-0.8 percentage change Standard Error 4.34	-13.1 percentage change Standard Error 4.22	-0.6 percentage change Standard Error 4.20	5.3 percentage change Standard Error 4.13
Percent Change From Baseline Over Time Through Week 48 in Fasting Total ApoB Week 20	-0.7 percentage change Standard Error 4.17	-10.3 percentage change Standard Error 4.10	4.4 percentage change Standard Error 4.06	1.6 percentage change Standard Error 3.98
Percent Change From Baseline Over Time Through Week 48 in Fasting Total ApoB Week 12	0.5 percentage change Standard Error 3.80	-11.2 percentage change Standard Error 3.74	-1.3 percentage change Standard Error 3.73	4.2 percentage change Standard Error 3.70

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). Participants with given assessment at given time point.

LDL-C analyses used both Martin-Hopkins methodology and ultracentrifugation. The Martin-Hopkins formula is a method for calculating LDL-C that improves accuracy by using an adjustable factor for estimating very-low-density lipoprotein (VLDL) cholesterol cholesterol based on triglyceride and non-HDL cholesterol levels.

Outcome measures

Outcome measures
Measure	ARO-APOC3 10 mg n=54 Participants Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg n=55 Participants Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg n=57 Participants Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	Placebo, Day 1 and Week 12 n=60 Participants Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
Percent Change From Baseline at Week 24 in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C) Martin-Hopkins methodology	301.9 percentage change Standard Error 128.17	-15.4 percentage change Standard Error 120.30	2.0 percentage change Standard Error 123.04	-5.5 percentage change Standard Error 123.7
Percent Change From Baseline at Week 24 in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C) Ultracentrifugation	49.0 percentage change Standard Error 11.06	43.7 percentage change Standard Error 10.76	78.2 percentage change Standard Error 10.60	18.0 percentage change Standard Error 10.48

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)

Population: Full Analysis Set: All randomized participants who receive at least 1 dose of investigational product (IP). Participants with given assessment at given time point.

LDL-C analyses used both Martin-Hopkins methodology (MHM) and ultracentrifugation (UC). The Martin-Hopkins formula is a method for calculating LDL-C that improves accuracy by using an adjustable factor for estimating very-low-density lipoprotein (VLDL) cholesterol cholesterol based on triglyceride and non-HDL cholesterol levels.

Outcome measures

Outcome measures
Measure	ARO-APOC3 10 mg n=54 Participants Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg n=55 Participants Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg n=57 Participants Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	Placebo, Day 1 and Week 12 n=60 Participants Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C MHM Week 20	306.7 percentage change Standard Error 128.15	-17.4 percentage change Standard Error 120.31	4.9 percentage change Standard Error 123.05	-7.3 percentage change Standard Error 123.72
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C MHM Week 24	301.9 percentage change Standard Error 128.17	-15.4 percentage change Standard Error 120.30	2.0 percentage change Standard Error 123.04	-5.5 percentage change Standard Error 123.67
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C MHM Week 4	267.3 percentage change Standard Error 128.13	-13.5 percentage change Standard Error 120.28	0.6 percentage change Standard Error 123.00	-29.3 percentage change Standard Error 123.78
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C MHM Week 8	297.4 percentage change Standard Error 128.11	-11.7 percentage change Standard Error 120.29	5.3 percentage change Standard Error 123.01	-11.3 percentage change Standard Error 123.74
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C MHM Week 12	300.7 percentage change Standard Error 128.12	-17.3 percentage change Standard Error 120.29	3.2 percentage change Standard Error 123.02	-13.6 percentage change Standard Error 123.75
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C MHM Week 16	340.3 percentage change Standard Error 128.15	-20.4 percentage change Standard Error 120.29	5.6 percentage change Standard Error 123.04	-14.3 percentage change Standard Error 123.72
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C MHM Week 28	283.2 percentage change Standard Error 128.20	-12.1 percentage change Standard Error 120.34	-4.7 percentage change Standard Error 123.06	-12.1 percentage change Standard Error 123.68
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C MHM Week 36	254.7 percentage change Standard Error 128.28	-0.7 percentage change Standard Error 120.38	1.6 percentage change Standard Error 123.10	-5.5 percentage change Standard Error 123.73
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C MHM Week 48	286.5 percentage change Standard Error 128.34	-9.0 percentage change Standard Error 120.44	-5.3 percentage change Standard Error 123.12	-11.5 percentage change Standard Error 123.77
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C UC Week 4	50.3 percentage change Standard Error 10.10	47.3 percentage change Standard Error 9.88	69.1 percentage change Standard Error 9.67	4.4 percentage change Standard Error 9.65
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C UC Week 8	49.8 percentage change Standard Error 10.92	45.8 percentage change Standard Error 10.73	65.4 percentage change Standard Error 10.51	15.8 percentage change Standard Error 10.44
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C UC Week 12	50.9 percentage change Standard Error 10.57	36.0 percentage change Standard Error 10.38	65.8 percentage change Standard Error 10.22	17.1 percentage change Standard Error 10.17
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C UC Week 16	62.6 percentage change Standard Error 12.80	41.7 percentage change Standard Error 12.46	87.1 percentage change Standard Error 12.31	19.3 percentage change Standard Error 12.14
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C UC Week 20	62.7 percentage change Standard Error 12.38	42.3 percentage change Standard Error 12.16	85.9 percentage change Standard Error 11.93	16.8 percentage change Standard Error 11.79
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C UC Week 24	49.0 percentage change Standard Error 11.06	43.7 percentage change Standard Error 10.76	78.2 percentage change Standard Error 10.60	18.0 percentage change Standard Error 10.48
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C UC Week 28	50.8 percentage change Standard Error 10.76	42.3 percentage change Standard Error 10.51	61.6 percentage change Standard Error 10.30	15.4 percentage change Standard Error 10.14
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C UC Week 36	35.5 percentage change Standard Error 10.47	51.5 percentage change Standard Error 10.20	61.3 percentage change Standard Error 9.97	18.4 percentage change Standard Error 9.89
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C UC Week 48	33.5 percentage change Standard Error 11.36	34.4 percentage change Standard Error 11.14	44.6 percentage change Standard Error 10.87	21.3 percentage change Standard Error 10.73

SECONDARY outcome

Timeframe: Day 1: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose; Week 12: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose

Population: Full PK Analysis Set: Full Analysis Set (FAS) participants (all randomized participants who received at least 1 dose of IP during the study period) who had sufficient plasma concentration data at given time point to facilitate determination of PK parameters.

Outcome measures

Outcome measures
Measure	ARO-APOC3 10 mg n=9 Participants Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg n=10 Participants Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	Placebo, Day 1 and Week 12 n=9 Participants Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12 Week 12, 3 Hours Post-Dose	42.591 ng/mL Standard Deviation 39.0808	65.482 ng/mL Standard Deviation 44.5255	—	15.101 ng/mL Standard Deviation 9.5156
Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12 Week 12, 6 Hours Post-Dose	56.230 ng/mL Standard Deviation 52.4345	73.444 ng/mL Standard Deviation 42.1339	—	11.131 ng/mL Standard Deviation 6.6894
Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12 Week 12, 24 Hours Post-Dose	6.241 ng/mL Standard Deviation 7.5820	12.125 ng/mL Standard Deviation 8.5500	—	3.143 ng/mL Standard Deviation 5.5271
Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12 Day 1, 15 Minutes Post-Dose	21.207 ng/mL Standard Deviation 21.7982	34.352 ng/mL Standard Deviation 27.3986	—	10.258 ng/mL Standard Deviation 12.4741
Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12 Week 12, 1 Hour Post-Dose	35.513 ng/mL Standard Deviation 26.5491	57.939 ng/mL Standard Deviation 26.8754	—	17.090 ng/mL Standard Deviation 12.7636
Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12 Day 1, Pre-Dose	0.000 ng/mL Standard Deviation 0.0000	0.000 ng/mL Standard Deviation 0.0000	—	0.000 ng/mL Standard Deviation 0.0000
Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12 Day 1, 1 Hour Post-Dose	37.396 ng/mL Standard Deviation 27.9849	58.508 ng/mL Standard Deviation 29.0222	—	18.124 ng/mL Standard Deviation 18.1760
Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12 Day 1, 3 Hours Post-Dose	50.596 ng/mL Standard Deviation 53.3270	58.493 ng/mL Standard Deviation 30.5510	—	20.217 ng/mL Standard Deviation 16.8127
Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12 Day 1, 6 Hours Post-Dose	51.813 ng/mL Standard Deviation 44.2610	64.019 ng/mL Standard Deviation 26.3749	—	17.147 ng/mL Standard Deviation 14.6145
Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12 Day 1, 24 Hours Post-Dose	10.316 ng/mL Standard Deviation 11.5852	11.587 ng/mL Standard Deviation 6.4288	—	7.921 ng/mL Standard Deviation 16.9181
Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12 Week 12, Pre-Dose	0.000 ng/mL Standard Deviation 0.0000	0.000 ng/mL Standard Deviation 0.0000	—	0.000 ng/mL Standard Deviation 0.0000
Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12 Week 12, 15 Minutes Post-Dose	23.576 ng/mL Standard Deviation 29.1713	38.500 ng/mL Standard Deviation 32.4047	—	10.188 ng/mL Standard Deviation 9.4024

SECONDARY outcome

Timeframe: From first dose of study drug up to Week 48

Population: Safety Analysis Set: All participants who receive at least 1 dose of IP.

An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with this treatment. A serious AE (SAE) is an AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is a medically important event or reaction. TEAEs are AEs that occur following investigational product (IP) administration or a pre-existing condition exacerbated following IP administration.

Outcome measures

Outcome measures
Measure	ARO-APOC3 10 mg n=54 Participants Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg n=55 Participants Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg n=56 Participants Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	Placebo, Day 1 and Week 12 n=61 Participants Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) All TEAEs	43 Participants	36 Participants	49 Participants	43 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Treatment-related TEAEs	13 Participants	8 Participants	10 Participants	8 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Serious TEAEs	4 Participants	2 Participants	7 Participants	10 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) TEAEs leading to study drug discontinuation	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Deaths	0 Participants	0 Participants	0 Participants	0 Participants

POST_HOC outcome

Timeframe: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)

Population: Full Analysis Set: All randomized participants who received at least 1 dose of investigational product (IP), excluding participants with values below the limit of quantification (BLQ) at Baseline, along with one site. Observed cases at given time point.

Outcome measures

Outcome measures
Measure	ARO-APOC3 10 mg n=53 Participants Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg n=55 Participants Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg n=57 Participants Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	Placebo, Day 1 and Week 12 n=57 Participants Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
Ad Hoc Analysis: Percent Change From Baseline at Week 24 and Over Time Through Week 48 in ApoC-III Week 4	-65.1 percentage change Standard Error 4.04	-82.9 percentage change Standard Error 3.94	-83.2 percentage change Standard Error 3.81	7.0 percentage change Standard Error 3.88
Ad Hoc Analysis: Percent Change From Baseline at Week 24 and Over Time Through Week 48 in ApoC-III Week 8	-57.3 percentage change Standard Error 4.36	-77.2 percentage change Standard Error 4.26	-78.7 percentage change Standard Error 4.14	4.7 percentage change Standard Error 4.19
Ad Hoc Analysis: Percent Change From Baseline at Week 24 and Over Time Through Week 48 in ApoC-III Week 12	-53.2 percentage change Standard Error 4.97	-70.3 percentage change Standard Error 4.84	-72.2 percentage change Standard Error 4.74	0.0 percentage change Standard Error 4.79
Ad Hoc Analysis: Percent Change From Baseline at Week 24 and Over Time Through Week 48 in ApoC-III Week 16	-74.8 percentage change Standard Error 4.13	-84.9 percentage change Standard Error 4.00	-86.3 percentage change Standard Error 3.92	2.8 percentage change Standard Error 3.94
Ad Hoc Analysis: Percent Change From Baseline at Week 24 and Over Time Through Week 48 in ApoC-III Week 20	-69.9 percentage change Standard Error 4.81	-79.7 percentage change Standard Error 4.72	-82.6 percentage change Standard Error 4.60	7.8 percentage change Standard Error 4.60
Ad Hoc Analysis: Percent Change From Baseline at Week 24 and Over Time Through Week 48 in ApoC-III Week 24	-68.1 percentage change Standard Error 4.51	-72.1 percentage change Standard Error 4.37	-78.2 percentage change Standard Error 4.26	-0.8 percentage change Standard Error 4.29
Ad Hoc Analysis: Percent Change From Baseline at Week 24 and Over Time Through Week 48 in ApoC-III Week 28	-63.0 percentage change Standard Error 4.42	-70.2 percentage change Standard Error 4.31	-73.2 percentage change Standard Error 4.19	-2.2 percentage change Standard Error 4.19
Ad Hoc Analysis: Percent Change From Baseline at Week 24 and Over Time Through Week 48 in ApoC-III Week 36	-48.5 percentage change Standard Error 5.23	-59.1 percentage change Standard Error 5.10	-58.3 percentage change Standard Error 4.95	0.2 percentage change Standard Error 4.98
Ad Hoc Analysis: Percent Change From Baseline at Week 24 and Over Time Through Week 48 in ApoC-III Week 48	-33.7 percentage change Standard Error 6.48	-48.0 percentage change Standard Error 6.37	-46.8 percentage change Standard Error 6.19	5.6 percentage change Standard Error 6.19

Adverse Events

ARO-APOC3 10 mg

Serious events: 4 serious events

Other events: 44 other events

Deaths: 0 deaths

ARO-APOC3 25 mg

Serious events: 2 serious events

Other events: 36 other events

Deaths: 0 deaths

ARO-APOC3 50 mg

Serious events: 7 serious events

Other events: 50 other events

Deaths: 0 deaths

Placebo, Day 1 and Week 12

Serious events: 10 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Operating Officer

Arrowhead Pharmaceuticals, Inc.

Phone: 1 (626) 304-3400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor retains first right to publish results for this multi-center study, and thereafter can review results communications prior to release and can embargo communications regarding trial results for a period that is 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication of results but can require removal of its confidential information (excluding results).
Publication restrictions are in place

Restriction type: OTHER

Measure	ARO-APOC3 10 mg n=54 participants at risk Participants received a total of 2 ARO-APOC3 10 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 25 mg n=55 participants at risk Participants received a total of 2 ARO-APOC3 25 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	ARO-APOC3 50 mg n=56 participants at risk Participants received a total of 2 ARO-APOC3 50 mg SC injections on Day 1 and Week 12 for a total of 2 injections.	Placebo, Day 1 and Week 12 n=61 participants at risk Participants received a total of 2 placebo SC injections on Day 1 and Week 12 for a total of 2 injections.
Cardiac disorders Angina unstable	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.6% 1/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Cardiac disorders Coronary artery disease	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.6% 1/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Cardiac disorders Coronary artery stenosis	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.6% 1/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Gastrointestinal disorders Abdominal pain	1.9% 1/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Gastrointestinal disorders Enteritis	1.9% 1/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.6% 1/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Gastrointestinal disorders Pancreatic pseudocyst	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.6% 1/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.8% 1/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.6% 1/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Gastrointestinal disorders Pancreatitis necrotising	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.6% 1/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Gastrointestinal disorders Pancreatitis relapsing	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.6% 1/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.8% 1/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Infections and infestations COVID-19	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.8% 1/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.6% 1/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Infections and infestations Pneumonia bacterial	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.8% 1/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Infections and infestations Sepsis	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.8% 1/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Injury, poisoning and procedural complications Concussion	1.9% 1/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.6% 1/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.8% 1/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.9% 1/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.8% 1/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer stage III	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.8% 1/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	1.9% 1/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.6% 1/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Nervous system disorders Cerebrovascular accident	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.8% 1/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Nervous system disorders Epilepsy	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.6% 1/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Nervous system disorders Ischaemic stroke	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.8% 1/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Renal and urinary disorders Acute kidney injury	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.8% 1/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Renal and urinary disorders Nephrolithiasis	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.8% 1/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.
Vascular disorders Peripheral artery thrombosis	0.00% 0/54 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/55 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	0.00% 0/56 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.	1.6% 1/61 • Up to 48 weeks Safety Analysis Set: All participants who receive at least 1 dose of IP, according to treatment actually given.