Trial Outcomes & Findings for Study of ARO-APOC3 (Plozasiran) in Adults With Familial Chylomicronemia Syndrome (FCS) (NCT NCT05089084)

NCT ID: NCT05089084

Last Updated: 2026-02-04

Results Overview

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

75 participants

Primary outcome timeframe

Baseline, Month 10

Results posted on

2026-02-04

Participant Flow

In the 12-month Randomized Period, participants who successfully passed eligibility requirements at screening enrolled in parallel cohorts, with participants randomly assigned 2:1:2:1 to plozasiran 25 mg, volume-matched placebo, plozasiran 50 mg and volume-matched placebo, respectively. Results data is presented for the Randomized Period; per protocol, placebo arms were pooled for this analysis. An Open-label Extension Period is ongoing.

Participant milestones

Participant milestones
Measure	Placebo (Pooled) Randomized Period: volume-matched placebo every 3 months (Q3M) for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Overall Study STARTED	25	26	24
Overall Study COMPLETED	19	23	22
Overall Study NOT COMPLETED	6	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo (Pooled) Randomized Period: volume-matched placebo every 3 months (Q3M) for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Overall Study Due to acute pancreatitis	3	0	0
Overall Study Due to other adverse event	0	2	1
Overall Study Withdrawal by Subject	3	0	0
Overall Study Pregnancy	0	1	0
Overall Study Other, not specified	0	0	1

Baseline Characteristics

Study of ARO-APOC3 (Plozasiran) in Adults With Familial Chylomicronemia Syndrome (FCS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo (Pooled) n=25 Participants Randomized Period: volume-matched placebo Q3M for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg n=26 Participants Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg n=24 Participants Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	Total n=75 Participants Total of all reporting groups
Age, Continuous	47.4 years STANDARD_DEVIATION 13.93 • n=41 Participants	47.9 years STANDARD_DEVIATION 14.41 • n=1581 Participants	42.6 years STANDARD_DEVIATION 10.85 • n=4626 Participants	46.0 years STANDARD_DEVIATION 13.24 • n=72 Participants
Sex: Female, Male Female	11 Participants n=41 Participants	14 Participants n=1581 Participants	13 Participants n=4626 Participants	38 Participants n=72 Participants
Sex: Female, Male Male	14 Participants n=41 Participants	12 Participants n=1581 Participants	11 Participants n=4626 Participants	37 Participants n=72 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=41 Participants	0 Participants n=1581 Participants	1 Participants n=4626 Participants	2 Participants n=72 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=41 Participants	26 Participants n=1581 Participants	22 Participants n=4626 Participants	72 Participants n=72 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=41 Participants	0 Participants n=1581 Participants	1 Participants n=4626 Participants	1 Participants n=72 Participants
Race/Ethnicity, Customized White	19 Participants n=41 Participants	19 Participants n=1581 Participants	17 Participants n=4626 Participants	55 Participants n=72 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=41 Participants	0 Participants n=1581 Participants	1 Participants n=4626 Participants	1 Participants n=72 Participants
Race/Ethnicity, Customized Asian	4 Participants n=41 Participants	7 Participants n=1581 Participants	5 Participants n=4626 Participants	16 Participants n=72 Participants
Race/Ethnicity, Customized Other, not specified	2 Participants n=41 Participants	0 Participants n=1581 Participants	1 Participants n=4626 Participants	3 Participants n=72 Participants
Triglycerides	2271.91 mg/dL STANDARD_DEVIATION 1141.426 • n=41 Participants	2349.53 mg/dL STANDARD_DEVIATION 1374.542 • n=1581 Participants	2491.45 mg/dL STANDARD_DEVIATION 1523.200 • n=4626 Participants	2369.07 mg/dL STANDARD_DEVIATION 1337.965 • n=72 Participants

PRIMARY outcome

Timeframe: Baseline, Month 10

Population: Full Analysis Set: all randomized participants regardless of adherence to the treatment, analyzed according to the treatment assigned at randomization. Participants with an assessment at baseline and Month 10.

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=19 Participants Randomized Period: volume-matched placebo Q3M for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg n=24 Participants Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg n=22 Participants Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Percent Change From Baseline at Month 10 in Fasting Triglycerides (TG)	-17.1 percentage change Interval -49.1 to 47.0	-80.1 percentage change Interval -89.9 to -61.0	-77.6 percentage change Interval -87.7 to -48.6

SECONDARY outcome

Timeframe: Baseline, Month 10, Month 12

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=19 Participants Randomized Period: volume-matched placebo Q3M for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg n=24 Participants Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg n=22 Participants Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Percent Change From Baseline in Fasting TG at Month 10 and Month 12 (Averaged)	-2.6 percentage change Interval -45.0 to 33.3	-77.7 percentage change Interval -89.0 to -59.2	-71.0 percentage change Interval -86.7 to -52.6

SECONDARY outcome

Timeframe: Baseline, Month 10

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=19 Participants Randomized Period: volume-matched placebo Q3M for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg n=24 Participants Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg n=22 Participants Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Percent Change From Baseline in Apolipoprotein C-III (APOC3) at Month 10	-1.25 percentage change Interval -16.59 to 26.46	-92.95 percentage change Interval -97.58 to -87.86	-96.20 percentage change Interval -97.71 to -89.88

SECONDARY outcome

Timeframe: Baseline, Month 12

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=19 Participants Randomized Period: volume-matched placebo Q3M for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg n=24 Participants Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg n=22 Participants Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Percent Change From Baseline in Fasting APOC3 at Month 12	7.69 percentage change Interval -33.65 to 31.28	-89.30 percentage change Interval -93.84 to -80.24	-87.73 percentage change Interval -93.01 to -78.7

SECONDARY outcome

Timeframe: From first dose of study drug through Month 12 (Randomized Period)

Population: Full Analysis Set: all randomized participants regardless of adherence to the treatment, analyzed according to the treatment assigned at randomization. The Statistical Analysis Plan pre-specified that the ARO-APOC3 25 mg and 50 mg groups were to be pooled together to be compared with placebo for the Randomized Period.

All adverse events (AEs) and serious adverse events (SAEs) reported by the Investigator during the study that are consistent with an event of acute pancreatitis will be adjudicated by a blinded, independent committee according to the 2013 Atlanta definition meeting 2 of the following 3 criteria: 1. Abdominal pain consistent with acute pancreatitis (acute onset of a persistent, severe, epigastric pain often radiating to the back) 2. Serum lipase activity (or amylase activity) ≥3 times the upper limit of normal (×ULN) 3. Characteristic findings of acute pancreatitis on contrast-enhanced computed tomography (CECT), magnetic resonance imaging (MRI), or transabdominal ultrasonography.

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=25 Participants Randomized Period: volume-matched placebo Q3M for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg n=50 Participants Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Percentage of Participants With Positively Adjudicated Events of Acute Pancreatitis (Randomized Period)	20.0 percentage of participants	4.0 percentage of participants	—

SECONDARY outcome

Timeframe: From first dose of study drug through Month 36 (Open-Label Period)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Month 10

Population: Full Analysis Set: all randomized participants regardless of adherence to the treatment, analyzed according to the treatment assigned at randomization. A pattern-mixture model is used as the imputation method for the missing values of Month 10 in fasting non-HDL-Cs.

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=25 Participants Randomized Period: volume-matched placebo Q3M for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg n=26 Participants Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg n=24 Participants Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Month 10	3.67 percentage change Standard Error 9.454	-38.69 percentage change Standard Error 7.980	-36.12 percentage change Standard Error 8.351

SECONDARY outcome

Timeframe: Baseline, Month 12

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=25 Participants Randomized Period: volume-matched placebo Q3M for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg n=26 Participants Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg n=24 Participants Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Percent Change From Baseline in Non-HDL-C at Month 12	6.72 percentage change Standard Error 9.373	-38.16 percentage change Standard Error 7.928	-25.48 percentage change Standard Error 8.368

SECONDARY outcome

Timeframe: Baseline, Month 10

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=25 Participants Randomized Period: volume-matched placebo Q3M for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg n=26 Participants Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg n=24 Participants Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Month 10	2.89 percentage change Standard Error 12.281	65.48 percentage change Standard Error 11.485	72.02 percentage change Standard Error 12.263

SECONDARY outcome

Timeframe: Baseline, Month 12

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=25 Participants Randomized Period: volume-matched placebo Q3M for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg n=26 Participants Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg n=24 Participants Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Percent Change From Baseline in HDL-C at Month 12	20.61 percentage change Standard Error 17.249	61.90 percentage change Standard Error 14.462	74.52 percentage change Standard Error 15.775

SECONDARY outcome

Timeframe: Baseline, Month 12

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=25 Participants Randomized Period: volume-matched placebo Q3M for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg n=26 Participants Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg n=24 Participants Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Percent Change From Baseline in Fasting Triglycerides (TG) at Month 12	0.72 percentage change Standard Error 15.962	-61.50 percentage change Standard Error 14.334	-45.38 percentage change Standard Error 14.542

SECONDARY outcome

Timeframe: Month 10

Population: Full Analysis Set: all randomized participants regardless of adherence to the treatment, analyzed according to the treatment assigned at randomization. Observed cases.

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=19 Participants Randomized Period: volume-matched placebo Q3M for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg n=24 Participants Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg n=22 Participants Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 10 <500 mg/dL (<5.6 mmol/L)	5.3 percentage of participants	50.0 percentage of participants	45.5 percentage of participants
Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 10 <880 mg/dL (<9.9 mmol/L)	21.1 percentage of participants	75.0 percentage of participants	54.5 percentage of participants
Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 10 <1000 mg/dL (<11.3 mmol/L)	31.6 percentage of participants	83.3 percentage of participants	68.2 percentage of participants

SECONDARY outcome

Timeframe: Month 12

Population: Full Analysis Set: all randomized participants regardless of adherence to the treatment, analyzed according to the treatment assigned at randomization. Observed cases.

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=19 Participants Randomized Period: volume-matched placebo Q3M for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg n=24 Participants Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg n=22 Participants Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 12 <500 mg/dL (<5.6 mmol/L)	10.5 percentage of participants	45.8 percentage of participants	40.9 percentage of participants
Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 12 <880 mg/dL (<9.9 mmol/L)	26.3 percentage of participants	75.0 percentage of participants	59.1 percentage of participants
Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 12 <1000 mg/dL (<11.3 mmol/L)	26.3 percentage of participants	75.0 percentage of participants	63.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Month 10

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=19 Participants Randomized Period: volume-matched placebo Q3M for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg n=24 Participants Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg n=22 Participants Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Percentage of Participants Achieving ≥40% and ≥70% Reduction From Baseline in Fasting TG at Month 10 ≥40% reduction from baseline fasting triglycerides	26.3 percentage of participants	95.8 percentage of participants	86.4 percentage of participants
Percentage of Participants Achieving ≥40% and ≥70% Reduction From Baseline in Fasting TG at Month 10 ≥70% reduction from baseline fasting triglycerides	10.5 percentage of participants	66.7 percentage of participants	54.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=24 Participants Randomized Period: volume-matched placebo Q3M for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg n=25 Participants Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg n=23 Participants Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Change From Baseline in Fasting TG Over Time Change at Month 5	-213.43 mg/dL Standard Error 216.851	-1613.90 mg/dL Standard Error 176.086	-1689.31 mg/dL Standard Error 330.096
Change From Baseline in Fasting TG Over Time Change at Month 6	-276.07 mg/dL Standard Error 205.490	-1566.97 mg/dL Standard Error 201.610	-1325.13 mg/dL Standard Error 215.809
Change From Baseline in Fasting TG Over Time Change at Month 7	324.98 mg/dL Standard Error 319.233	-1842.65 mg/dL Standard Error 210.671	-1691.87 mg/dL Standard Error 285.252
Change From Baseline in Fasting TG Over Time Change at Month 8	188.62 mg/dL Standard Error 271.286	-1537.57 mg/dL Standard Error 190.088	-1133.96 mg/dL Standard Error 279.984
Change From Baseline in Fasting TG Over Time Change at Month 9	-119.48 mg/dL Standard Error 226.547	-1413.87 mg/dL Standard Error 232.426	-1650.75 mg/dL Standard Error 329.600
Change From Baseline in Fasting TG Over Time Change at Month 10	-248.35 mg/dL Standard Error 233.539	-1819.82 mg/dL Standard Error 227.632	-1740.20 mg/dL Standard Error 293.567
Change From Baseline in Fasting TG Over Time Change at Month 11	173.14 mg/dL Standard Error 336.713	-1810.57 mg/dL Standard Error 296.726	-1507.08 mg/dL Standard Error 203.964
Change From Baseline in Fasting TG Over Time Change at Month 12	-50.32 mg/dL Standard Error 273.674	-1637.18 mg/dL Standard Error 274.479	-1485.30 mg/dL Standard Error 339.662
Change From Baseline in Fasting TG Over Time Change at Month 1	180.81 mg/dL Standard Error 247.835	-1898.79 mg/dL Standard Error 205.603	-1759.36 mg/dL Standard Error 277.758
Change From Baseline in Fasting TG Over Time Change at Month 2	-203.67 mg/dL Standard Error 195.740	-1519.38 mg/dL Standard Error 203.397	-1481.57 mg/dL Standard Error 218.704
Change From Baseline in Fasting TG Over Time Change at Month 3	392.98 mg/dL Standard Error 320.073	-1177.43 mg/dL Standard Error 212.134	-1478.94 mg/dL Standard Error 276.681
Change From Baseline in Fasting TG Over Time Change at Month 4	-248.76 mg/dL Standard Error 198.553	-1521.25 mg/dL Standard Error 291.471	-1810.31 mg/dL Standard Error 245.695

SECONDARY outcome

Timeframe: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=24 Participants Randomized Period: volume-matched placebo Q3M for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg n=25 Participants Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg n=23 Participants Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Percent Change From Baseline in Fasting TG Over Time Percent Change at Month 1	13.21 percentage change Standard Error 14.003	-81.43 percentage change Standard Error 2.854	-68.21 percentage change Standard Error 5.390
Percent Change From Baseline in Fasting TG Over Time Percent Change at Month 2	-7.30 percentage change Standard Error 10.375	-69.33 percentage change Standard Error 5.119	-62.96 percentage change Standard Error 5.940
Percent Change From Baseline in Fasting TG Over Time Percent Change at Month 3	14.66 percentage change Standard Error 12.028	-57.13 percentage change Standard Error 7.424	-60.94 percentage change Standard Error 6.761
Percent Change From Baseline in Fasting TG Over Time Percent Change at Month 4	-1.74 percentage change Standard Error 8.861	-68.27 percentage change Standard Error 8.795	-71.91 percentage change Standard Error 5.076
Percent Change From Baseline in Fasting TG Over Time Percent Change at Month 5	-9.23 percentage change Standard Error 9.561	-71.96 percentage change Standard Error 5.052	-60.41 percentage change Standard Error 10.796
Percent Change From Baseline in Fasting TG Over Time Percent Change at Month 6	-6.18 percentage change Standard Error 12.679	-68.08 percentage change Standard Error 4.884	-56.30 percentage change Standard Error 6.317
Percent Change From Baseline in Fasting TG Over Time Percent Change at Month 7	21.45 percentage change Standard Error 15.235	-77.44 percentage change Standard Error 4.082	-65.88 percentage change Standard Error 5.863
Percent Change From Baseline in Fasting TG Over Time Percent Change at Month 8	14.98 percentage change Standard Error 13.745	-68.35 percentage change Standard Error 4.805	-47.77 percentage change Standard Error 11.563
Percent Change From Baseline in Fasting TG Over Time Percent Change at Month 9	4.08 percentage change Standard Error 12.059	-55.32 percentage change Standard Error 8.363	-62.72 percentage change Standard Error 7.369
Percent Change From Baseline in Fasting TG Over Time Percent Change at Month 10	-8.74 percentage change Standard Error 11.466	-74.45 percentage change Standard Error 4.135	-66.53 percentage change Standard Error 5.951
Percent Change From Baseline in Fasting TG Over Time Percent Change at Month 11	10.40 percentage change Standard Error 16.139	-68.39 percentage change Standard Error 6.776	-63.83 percentage change Standard Error 6.143
Percent Change From Baseline in Fasting TG Over Time Percent Change at Month 12	0.93 percentage change Standard Error 14.858	-67.69 percentage change Standard Error 5.985	-50.60 percentage change Standard Error 14.269

SECONDARY outcome

Timeframe: From first dose of study drug through Month 12 (Randomized Period)

Population: Safety Analysis Set: all randomized participants who received at least 1 dose of study drug, analyzed according to the treatment they actually received.

AE: any untoward medical occurrence which does not necessarily have to have a causal relationship with treatment. Treatment-emergent AEs (TEAEs): AEs with onset after administration of the study drug, or when a preexisting medical condition increases in severity or frequency after study drug administration. SAE: AE that fulfills one or more of the following: results in death; is immediately life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; is an important medical event that may jeopardize the patient or may require medical intervention to prevent one of the outcomes listed above. Severity was reported as: mild, moderate, severe, life threatening, death.

Outcome measures

Outcome measures
Measure	Placebo (Pooled) n=25 Participants Randomized Period: volume-matched placebo Q3M for a total of 4 doses. Open-label Period: plozasiran 25 mg or 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 25 mg n=26 Participants Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.	ARO-APOC3 (Plozasiran) 50 mg n=24 Participants Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses. Open-label Period: plozasiran 50 mg (Part A), then 25 mg (Part B) Q3M for a total of 8 doses.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs; Randomized Period) All TEAEs	20 Participants	23 Participants	20 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs; Randomized Period) Treatment-related TEAEs	6 Participants	7 Participants	8 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs; Randomized Period) Serious TEAEs	7 Participants	5 Participants	2 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs; Randomized Period) TEAEs leading to study drug discontinuation	0 Participants	2 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs; Randomized Period) TEAEs leading to study termination	0 Participants	2 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs; Randomized Period) TEAEs of clinical interest	1 Participants	4 Participants	2 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs; Randomized Period) Any TEAE by maximum severity: Mild	5 Participants	13 Participants	13 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs; Randomized Period) Any TEAE by maximum severity: Moderate	10 Participants	7 Participants	4 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs; Randomized Period) Any TEAE by maximum severity: Severe	5 Participants	2 Participants	3 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs; Randomized Period) Any TEAE by maximum severity: Life Threatening	0 Participants	1 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs; Randomized Period) Any TEAE by maximum severity: Death	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of open-label study drug through Month 36 (Open-Label Period)

Outcome measures

Outcome data not reported

Adverse Events

Placebo (Pooled)

Serious events: 7 serious events

Other events: 17 other events

Deaths: 0 deaths

ARO-APOC3 (Plozasiran) 25 mg

Serious events: 5 serious events

Other events: 21 other events

Deaths: 0 deaths

ARO-APOC3 (Plozasiran) 50 mg

Serious events: 2 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo (Pooled) n=25 participants at risk Randomized Period: volume-matched placebo Q3M for a total of 4 doses.	ARO-APOC3 (Plozasiran) 25 mg n=26 participants at risk Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses.	ARO-APOC3 (Plozasiran) 50 mg n=24 participants at risk Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses.
Immune system disorders Anaphylactic shock	4.0% 1/25 • Screening through Month 12 (Randomized Period)	0.00% 0/26 • Screening through Month 12 (Randomized Period)	0.00% 0/24 • Screening through Month 12 (Randomized Period)
Infections and infestations Cellulitis	0.00% 0/25 • Screening through Month 12 (Randomized Period)	0.00% 0/26 • Screening through Month 12 (Randomized Period)	4.2% 1/24 • Screening through Month 12 (Randomized Period)
Infections and infestations Tooth abscess	0.00% 0/25 • Screening through Month 12 (Randomized Period)	0.00% 0/26 • Screening through Month 12 (Randomized Period)	4.2% 1/24 • Screening through Month 12 (Randomized Period)
Gastrointestinal disorders Pancreatitis relapsing	12.0% 3/25 • Screening through Month 12 (Randomized Period)	0.00% 0/26 • Screening through Month 12 (Randomized Period)	4.2% 1/24 • Screening through Month 12 (Randomized Period)
Gastrointestinal disorders Large intestine polyp	4.0% 1/25 • Screening through Month 12 (Randomized Period)	0.00% 0/26 • Screening through Month 12 (Randomized Period)	0.00% 0/24 • Screening through Month 12 (Randomized Period)
Gastrointestinal disorders Pancreatitis	4.0% 1/25 • Screening through Month 12 (Randomized Period)	0.00% 0/26 • Screening through Month 12 (Randomized Period)	0.00% 0/24 • Screening through Month 12 (Randomized Period)
Cardiac disorders Acute myocardial infarction	0.00% 0/25 • Screening through Month 12 (Randomized Period)	3.8% 1/26 • Screening through Month 12 (Randomized Period)	0.00% 0/24 • Screening through Month 12 (Randomized Period)
Cardiac disorders Coronary artery disease	0.00% 0/25 • Screening through Month 12 (Randomized Period)	3.8% 1/26 • Screening through Month 12 (Randomized Period)	0.00% 0/24 • Screening through Month 12 (Randomized Period)
Cardiac disorders Coronary artery stenosis	4.0% 1/25 • Screening through Month 12 (Randomized Period)	0.00% 0/26 • Screening through Month 12 (Randomized Period)	0.00% 0/24 • Screening through Month 12 (Randomized Period)
Gastrointestinal disorders Pancreatitis acute	12.0% 3/25 • Screening through Month 12 (Randomized Period)	7.7% 2/26 • Screening through Month 12 (Randomized Period)	0.00% 0/24 • Screening through Month 12 (Randomized Period)
Injury, poisoning and procedural complications Intentional overdose	0.00% 0/25 • Screening through Month 12 (Randomized Period)	3.8% 1/26 • Screening through Month 12 (Randomized Period)	0.00% 0/24 • Screening through Month 12 (Randomized Period)
Injury, poisoning and procedural complications Vascular graft occlusion	0.00% 0/25 • Screening through Month 12 (Randomized Period)	3.8% 1/26 • Screening through Month 12 (Randomized Period)	0.00% 0/24 • Screening through Month 12 (Randomized Period)
Reproductive system and breast disorders Prostatitis	4.0% 1/25 • Screening through Month 12 (Randomized Period)	0.00% 0/26 • Screening through Month 12 (Randomized Period)	0.00% 0/24 • Screening through Month 12 (Randomized Period)
Respiratory, thoracic and mediastinal disorders Laryngeal oedema	0.00% 0/25 • Screening through Month 12 (Randomized Period)	0.00% 0/26 • Screening through Month 12 (Randomized Period)	4.2% 1/24 • Screening through Month 12 (Randomized Period)

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	Placebo (Pooled) n=25 participants at risk Randomized Period: volume-matched placebo Q3M for a total of 4 doses.	ARO-APOC3 (Plozasiran) 25 mg n=26 participants at risk Randomized Period: plozasiran 25 mg Q3M for a total of 4 doses.	ARO-APOC3 (Plozasiran) 50 mg n=24 participants at risk Randomized Period: plozasiran 50 mg Q3M for a total of 4 doses.
Gastrointestinal disorders Abdominal pain upper	4.0% 1/25 • Screening through Month 12 (Randomized Period)	0.00% 0/26 • Screening through Month 12 (Randomized Period)	8.3% 2/24 • Screening through Month 12 (Randomized Period)
General disorders Fatigue	8.0% 2/25 • Screening through Month 12 (Randomized Period)	3.8% 1/26 • Screening through Month 12 (Randomized Period)	8.3% 2/24 • Screening through Month 12 (Randomized Period)
General disorders Injection site pain	4.0% 1/25 • Screening through Month 12 (Randomized Period)	7.7% 2/26 • Screening through Month 12 (Randomized Period)	4.2% 1/24 • Screening through Month 12 (Randomized Period)
General disorders Injection site reaction	0.00% 0/25 • Screening through Month 12 (Randomized Period)	7.7% 2/26 • Screening through Month 12 (Randomized Period)	0.00% 0/24 • Screening through Month 12 (Randomized Period)
General disorders Oedema peripheral	0.00% 0/25 • Screening through Month 12 (Randomized Period)	7.7% 2/26 • Screening through Month 12 (Randomized Period)	0.00% 0/24 • Screening through Month 12 (Randomized Period)
Infections and infestations COVID-19	4.0% 1/25 • Screening through Month 12 (Randomized Period)	19.2% 5/26 • Screening through Month 12 (Randomized Period)	29.2% 7/24 • Screening through Month 12 (Randomized Period)
Infections and infestations Nasopharyngitis	16.0% 4/25 • Screening through Month 12 (Randomized Period)	19.2% 5/26 • Screening through Month 12 (Randomized Period)	8.3% 2/24 • Screening through Month 12 (Randomized Period)
Infections and infestations Upper respiratory tract infection	8.0% 2/25 • Screening through Month 12 (Randomized Period)	11.5% 3/26 • Screening through Month 12 (Randomized Period)	8.3% 2/24 • Screening through Month 12 (Randomized Period)
Infections and infestations Gastroenteritis	4.0% 1/25 • Screening through Month 12 (Randomized Period)	3.8% 1/26 • Screening through Month 12 (Randomized Period)	8.3% 2/24 • Screening through Month 12 (Randomized Period)
Infections and infestations Urinary tract infection	8.0% 2/25 • Screening through Month 12 (Randomized Period)	0.00% 0/26 • Screening through Month 12 (Randomized Period)	8.3% 2/24 • Screening through Month 12 (Randomized Period)
Infections and infestations Bronchitis	8.0% 2/25 • Screening through Month 12 (Randomized Period)	0.00% 0/26 • Screening through Month 12 (Randomized Period)	4.2% 1/24 • Screening through Month 12 (Randomized Period)
Infections and infestations Influenza	0.00% 0/25 • Screening through Month 12 (Randomized Period)	3.8% 1/26 • Screening through Month 12 (Randomized Period)	8.3% 2/24 • Screening through Month 12 (Randomized Period)
Investigations Glycosylated haemoglobin increased	0.00% 0/25 • Screening through Month 12 (Randomized Period)	11.5% 3/26 • Screening through Month 12 (Randomized Period)	12.5% 3/24 • Screening through Month 12 (Randomized Period)
Investigations Blood creatine phosphokinase increased	0.00% 0/25 • Screening through Month 12 (Randomized Period)	0.00% 0/26 • Screening through Month 12 (Randomized Period)	8.3% 2/24 • Screening through Month 12 (Randomized Period)
Musculoskeletal and connective tissue disorders Back pain	8.0% 2/25 • Screening through Month 12 (Randomized Period)	11.5% 3/26 • Screening through Month 12 (Randomized Period)	8.3% 2/24 • Screening through Month 12 (Randomized Period)
Musculoskeletal and connective tissue disorders Arthralgia	8.0% 2/25 • Screening through Month 12 (Randomized Period)	3.8% 1/26 • Screening through Month 12 (Randomized Period)	4.2% 1/24 • Screening through Month 12 (Randomized Period)
Musculoskeletal and connective tissue disorders Pain in extremity	4.0% 1/25 • Screening through Month 12 (Randomized Period)	3.8% 1/26 • Screening through Month 12 (Randomized Period)	8.3% 2/24 • Screening through Month 12 (Randomized Period)
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/25 • Screening through Month 12 (Randomized Period)	0.00% 0/26 • Screening through Month 12 (Randomized Period)	8.3% 2/24 • Screening through Month 12 (Randomized Period)
Nervous system disorders Headache	8.0% 2/25 • Screening through Month 12 (Randomized Period)	11.5% 3/26 • Screening through Month 12 (Randomized Period)	20.8% 5/24 • Screening through Month 12 (Randomized Period)
Nervous system disorders Dizziness	4.0% 1/25 • Screening through Month 12 (Randomized Period)	7.7% 2/26 • Screening through Month 12 (Randomized Period)	4.2% 1/24 • Screening through Month 12 (Randomized Period)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/25 • Screening through Month 12 (Randomized Period)	7.7% 2/26 • Screening through Month 12 (Randomized Period)	0.00% 0/24 • Screening through Month 12 (Randomized Period)
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/25 • Screening through Month 12 (Randomized Period)	7.7% 2/26 • Screening through Month 12 (Randomized Period)	0.00% 0/24 • Screening through Month 12 (Randomized Period)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/25 • Screening through Month 12 (Randomized Period)	7.7% 2/26 • Screening through Month 12 (Randomized Period)	0.00% 0/24 • Screening through Month 12 (Randomized Period)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/25 • Screening through Month 12 (Randomized Period)	7.7% 2/26 • Screening through Month 12 (Randomized Period)	8.3% 2/24 • Screening through Month 12 (Randomized Period)
Skin and subcutaneous tissue disorders Xanthoma	0.00% 0/25 • Screening through Month 12 (Randomized Period)	7.7% 2/26 • Screening through Month 12 (Randomized Period)	0.00% 0/24 • Screening through Month 12 (Randomized Period)
Vascular disorders Hypertension	8.0% 2/25 • Screening through Month 12 (Randomized Period)	7.7% 2/26 • Screening through Month 12 (Randomized Period)	4.2% 1/24 • Screening through Month 12 (Randomized Period)
Gastrointestinal disorders Constipation	4.0% 1/25 • Screening through Month 12 (Randomized Period)	7.7% 2/26 • Screening through Month 12 (Randomized Period)	4.2% 1/24 • Screening through Month 12 (Randomized Period)
Gastrointestinal disorders Vomiting	4.0% 1/25 • Screening through Month 12 (Randomized Period)	7.7% 2/26 • Screening through Month 12 (Randomized Period)	4.2% 1/24 • Screening through Month 12 (Randomized Period)
Gastrointestinal disorders Abdominal discomfort	0.00% 0/25 • Screening through Month 12 (Randomized Period)	0.00% 0/26 • Screening through Month 12 (Randomized Period)	12.5% 3/24 • Screening through Month 12 (Randomized Period)
Cardiac disorders Palpitations	0.00% 0/25 • Screening through Month 12 (Randomized Period)	11.5% 3/26 • Screening through Month 12 (Randomized Period)	0.00% 0/24 • Screening through Month 12 (Randomized Period)
Gastrointestinal disorders Abdominal pain	28.0% 7/25 • Screening through Month 12 (Randomized Period)	26.9% 7/26 • Screening through Month 12 (Randomized Period)	29.2% 7/24 • Screening through Month 12 (Randomized Period)
Gastrointestinal disorders Nausea	8.0% 2/25 • Screening through Month 12 (Randomized Period)	15.4% 4/26 • Screening through Month 12 (Randomized Period)	12.5% 3/24 • Screening through Month 12 (Randomized Period)
Gastrointestinal disorders Diarrhoea	8.0% 2/25 • Screening through Month 12 (Randomized Period)	3.8% 1/26 • Screening through Month 12 (Randomized Period)	16.7% 4/24 • Screening through Month 12 (Randomized Period)