CompletedNCT05089084PALISADEUpdated Jun 5, 2026Results posted

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

A Phase 3 interventional study of Plozasiran and Placebo in Familial Chylomicronemia, sponsored by Arrowhead Pharmaceuticals. Completed at 58 sites in 21 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-05.

Sponsored by Arrowhead Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 75
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

The purpose of AROAPOC3-3001 is to evaluate the efficacy and safety of ARO-APOC3 (plozasiran) in adult participants with familial chylomicronemia syndrome (FCS). Participants who have met all eligibility criteria will be randomized to receive 4 doses of plozasiran or matching placebo administered subcutaneously. Participants who complete the randomized period will continue in a 2-year open-label extension period where all participants will receive plozasiran.

Conditions studied

Familial Chylomicronemia

Browse trials for

Hyperlipoproteinemia Type I 23

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Fasting triglycerides (TG) ≥ 10 mmol/L (≥ 880 mg/dL) at screening refractory to standard lipid lowering therapy
Diagnosis of FCS
Willing to follow dietary counseling as per investigator judgement based on local standard of care
Participants of childbearing potential (males \& females) must use highly-effective contraception during the study and for at least 24 weeks following the last dose of study medication. Males must not donate sperm during the study and for at least 24 weeks following the last dose of study medication
Women of childbearing potential must have a negative pregnancy test at Screening and cannot be breastfeeding
Women of childbearing potential on hormonal contraceptives must be stable on the medication for ≥ 2 menstrual cycles prior to Day 1

Exclusion criteria

Exclusion Criteria:

Current use or use within the last 365 Days from Day 1 of any hepatocyte-targeted siRNA or antisense oligonucleotide molecule
Diabetes mellitus newly diagnosed within 12 weeks of Screening or where HbA1c ≥ 9.0% at Screening
Active pancreatitis within 12 weeks before Day 1
History of acute coronary syndrome event within 24 weeks of Day 1
History of major surgery within 12 weeks of Day 1
Uncontrolled hypertension
On treatment with human immunodeficiency virus (HIV) antiretroviral therapy
Seropositive for hepatitis B virus (HBV) or hepatitis C virus (HCV)
New York Heart Association (NYHA) Clas II, III, or IV heart failure

Note: Additional Inclusion/Exclusion criteria may apply per protocol

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 75 participants (actual)

Study arms

Experimental
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.
Drug: Plozasiran
Placebo comparator
Placebo for ARO-APOC3 (Plozasiran) 25 mg
Randomized Period: volume-matched placebo every 3 months (Q3M) for a total of 4 doses. Open-label Period (Parts A and B): plozasiran 25 mg Q3M for a total of 8 doses.
Drug: Plozasiran · Drug: Placebo
Experimental
ARO-APOC3 (Plozasiran) 50 mg
Randomized Period: plozasiran 25 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.
Drug: Plozasiran
Placebo comparator
Placebo for ARO-APOC3 (Plozasiran) 50 mg
Randomized Period: volume-matched placebo every 3 months (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.
Drug: Plozasiran · Drug: Placebo

Interventions

DrugPlozasiran
ARO-APOC3 subcutaneous (SC) injection
Also known as: ARO-APOC3
DrugPlacebo
sterile normal saline (0.9% NaCl) SC injection

What researchers measure

Primary outcomes

Percent Change From Baseline at Month 10 in Fasting Triglycerides (TG)
Time frame: Baseline, Month 10

Secondary outcomes

Percent Change From Baseline in Fasting TG at Month 10 and Month 12 (Averaged)
Time frame: Baseline, Month 10, Month 12
Percent Change From Baseline in Apolipoprotein C-III (APOC3) at Month 10
Time frame: Baseline, Month 10
Percent Change From Baseline in Fasting APOC3 at Month 12
Time frame: Baseline, Month 12
Percentage of Participants With Positively Adjudicated Events of Acute Pancreatitis (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.
Time frame: From first dose of study drug through Month 12 (Randomized Period)
Percentage of Participants With Positively Adjudicated Events of Acute Pancreatitis (Open-Label 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.
Time frame: From first dose of study drug through Month 36 (Open-Label Period)
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Month 10
Time frame: Baseline, Month 10
Percent Change From Baseline in Non-HDL-C at Month 12
Time frame: Baseline, Month 12
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Month 10
Time frame: Baseline, Month 10
Percent Change From Baseline in HDL-C at Month 12
Time frame: Baseline, Month 12
Percent Change From Baseline in Fasting Triglycerides (TG) at Month 12
Time frame: Baseline, Month 12
Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 10
Time frame: Month 10
Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 12
Time frame: Month 12
Percentage of Participants Achieving ≥40% and ≥70% Reduction From Baseline in Fasting TG at Month 10
Time frame: Baseline, Month 10
Change From Baseline in Fasting TG Over Time
Time frame: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Percent Change From Baseline in Fasting TG Over Time
Time frame: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Number of Participants With Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs; Randomized Period)
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.
Time frame: From first dose of study drug through Month 12 (Randomized Period)
Number of Participants With Treatment-Emergent AEs and/or SAEs (Open-Label Period)
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.
Time frame: From first dose of open-label study drug through Month 36 (Open-Label Period)

Results

Posted Feb 4, 2026

Participant flow

Participant flow — Overall Study
Milestone	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
Started	25	26	24
Completed	19	23	22
Not completed	6	3	2
Withdrew: Due to acute pancreatitis	3	0	0
Withdrew: Due to other adverse event	0	2	1
Withdrew: Withdrawal by subject	3	0	0
Withdrew: Pregnancy	0	1	0
Withdrew: Other, not specified	0	0	1

Outcome measures

PrimaryPercent Change From Baseline at Month 10 in Fasting Triglycerides (TG)

Time frame:: Baseline, Month 10
Reported as:: Median · percentage change

Percent Change From Baseline at Month 10 in Fasting Triglycerides (TG)
percentage change	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
Percent Change From Baseline at Month 10 in Fasting Triglycerides (TG)	-17.1 (-49.1 to 47.0)	-80.1 (-89.9 to -61.0)	-77.6 (-87.7 to -48.6)

Statistical analysis

Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · Wilcoxon rank-sum test · p = < 0.0001 · Median difference (final values): -58.7 · 95% CI -89.6 to -27.9Hodges-Lehmann method was used to estimate the median difference (location shift) and its corresponding 95% confidence interval for percent changes between plozasiran doses and placebo (pooled).
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · Holm method · p = <0.0001 (The adjusted p-value was calculated using the Holm method for multiplicity adjustment.)
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · Wilcoxon rank-sum test · p = 0.0002 · Median difference (final values): -52.5 · 95% CI -83.1 to -21.9Hodges-Lehmann method was used to estimate the median difference (location shift) and its corresponding 95% confidence interval for percent changes between plozasiran doses and placebo (pooled).
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · Holm method · p = 0.0002 (The adjusted p-value was calculated using the Holm method for multiplicity adjustment.)

SecondaryPercent Change From Baseline in Fasting TG at Month 10 and Month 12 (Averaged)

Time frame:: Baseline, Month 10, Month 12
Reported as:: Median · percentage change

Percent Change From Baseline in Fasting TG at Month 10 and Month 12 (Averaged)
percentage change	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
Percent Change From Baseline in Fasting TG at Month 10 and Month 12 (Averaged)	-2.6 (-45.0 to 33.3)	-77.7 (-89.0 to -59.2)	-71.0 (-86.7 to -52.6)

Statistical analysis

Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · Wilcoxon rank-sum test · p = <0.0001 · Median difference (final values): -59.6 · 95% CI -91.6 to -27.5Hodges-Lehmann method was used to estimate the median difference (location shift) and its corresponding 95% CI for percent changes between plozasiran doses and placebo (pooled).
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · Holm method · p = <0.0001 (The adjusted p-value was calculated using the Holm method for multiplicity adjustment.)
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · Wilcoxon rank-sum test · p = 0.0007 · Median difference (final values): -50.8 · 95% CI -83.5 to -18.1Hodges-Lehmann method was used to estimate the median difference (location shift) and its corresponding 95% CI for percent changes between plozasiran doses and placebo (pooled).
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · Holm method · p = 0.0007 (The adjusted p-value was calculated using the Holm method for multiplicity adjustment.)

SecondaryPercent Change From Baseline in Apolipoprotein C-III (APOC3) at Month 10

Time frame:: Baseline, Month 10
Reported as:: Median · percentage change

Percent Change From Baseline in Apolipoprotein C-III (APOC3) at Month 10
percentage change	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
Percent Change From Baseline in Apolipoprotein C-III (APOC3) at Month 10	-1.25 (-16.59 to 26.46)	-92.95 (-97.58 to -87.86)	-96.20 (-97.71 to -89.88)

Statistical analysis

Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · Wilcoxon rank-sum test · p = <0.0001 · Median difference (final values): -90.48 · 95% CI -108.29 to -72.67Hodges-Lehmann method was used to estimate the median difference (location shift) and its corresponding 95% CI for percent changes between plozasiran doses and placebo (pooled).
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · Holm method · p = <0.0001 (The adjusted p-value was calculated using the Holm method for multiplicity adjustment.)
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · Wilcoxon rank-sum test · p = <0.0001 · Median difference (final values): -93.40 · 95% CI -109.38 to -77.42Hodges-Lehmann method was used to estimate the median difference (location shift) and its corresponding 95% CI for percent changes between plozasiran doses and placebo (pooled).
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · Holm method · p = <0.0001 (The adjusted p-value was calculated using the Holm method for multiplicity adjustment.)

SecondaryPercent Change From Baseline in Fasting APOC3 at Month 12

Time frame:: Baseline, Month 12
Reported as:: Median · percentage change

Percent Change From Baseline in Fasting APOC3 at Month 12
percentage change	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
Percent Change From Baseline in Fasting APOC3 at Month 12	7.69 (-33.65 to 31.28)	-89.30 (-93.84 to -80.24)	-87.73 (-93.01 to -78.70)

Statistical analysis

Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · Wilcoxon rank-sum test · p = <0.0001 · Median difference (final values): -86.95 · 95% CI -112.93 to -60.96Hodges-Lehmann method was used to estimate the median difference (location shift) and its corresponding 95% CI for percent changes between plozasiran doses and placebo (pooled).
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · Holm method · p = <0.0001 (The adjusted p-value was calculated using the Holm method for multiplicity adjustment.)
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · Wilcoxon rank-sum test · p = <0.0001 · Median difference (final values): -87.48 · 95% CI -112.42 to -62.54Hodges-Lehmann method was used to estimate the median difference (location shift) and its corresponding 95% CI for percent changes between plozasiran doses and placebo (pooled).
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · Holm method · p = <0.0001 (The adjusted p-value was calculated using the Holm method for multiplicity adjustment.)

SecondaryPercentage of Participants With Positively Adjudicated Events of Acute Pancreatitis (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.

Time frame:: From first dose of study drug through Month 12 (Randomized Period)
Reported as:: Number · percentage of participants

Percentage of Participants With Positively Adjudicated Events of Acute Pancreatitis (Randomized Period)
percentage of participants	Placebo (Pooled)	ARO-APOC3 (Plozasiran) Pooled
Percentage of Participants With Positively Adjudicated Events of Acute Pancreatitis (Randomized Period)	20.0	4.0

Statistical analysis

Placebo (Pooled) vs ARO-APOC3 (Plozasiran) Pooled · Cochran-Mantel-Haenszel · p = 0.0292 (Odds ratio, 95% confidence interval (CI), and P-value were based on Cochran-Mantel-Haenszel (CMH) test stratified by baseline triglyceride category.) · Odds ratio (or): 0.169 · 95% CI 0.030 to 0.942

SecondaryPercentage of Participants With Positively Adjudicated Events of Acute Pancreatitis (Open-Label Period)

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

Results for this outcome have not been posted.

SecondaryPercent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Month 10

Time frame:: Baseline, Month 10
Reported as:: Least squares mean · percentage change

Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Month 10
percentage change	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Month 10	3.67 ± 9.454	-38.69 ± 7.980	-36.12 ± 8.351

Statistical analysis

Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · ANCOVA · p = 0.0007 (ANCOVA with Pattern-mixture Model) · Least squares (ls) mean difference: -42.36 · 95% CI -66.70 to -18.01
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · ANCOVA · p = 0.0018 (ANCOVA with Pattern-mixture Model) · Ls mean difference: -39.79 · 95% CI -64.72 to -14.87

SecondaryPercent Change From Baseline in Non-HDL-C at Month 12

Time frame:: Baseline, Month 12
Reported as:: Least squares mean · percentage change

Percent Change From Baseline in Non-HDL-C at Month 12
percentage change	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
Percent Change From Baseline in Non-HDL-C at Month 12	6.72 ± 9.373	-38.16 ± 7.928	-25.48 ± 8.368

Statistical analysis

Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · ANCOVA · p = 0.0003 (ANCOVA with Pattern-mixture Model) · Ls mean difference: -44.88 · 95% CI -68.86 to -20.89
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · ANCOVA · p = 0.0114 (ANCOVA with Pattern-mixture Model) · Ls mean difference: -32.19 · 95% CI -57.13 to -7.25

SecondaryPercent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Month 10

Time frame:: Baseline, Month 10
Reported as:: Least squares mean · percentage change

Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Month 10
percentage change	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Month 10	2.89 ± 12.281	65.48 ± 11.485	72.02 ± 12.263

Statistical analysis

Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · ANCOVA · p = 0.0002 (ANCOVA with Pattern-mixture Model) · Ls mean difference: 62.60 · 95% CI 29.68 to 95.52
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · ANCOVA · p = <0.0001 (ANCOVA with Pattern-mixture Model) · Ls mean difference: 69.14 · 95% CI 34.85 to 103.42

SecondaryPercent Change From Baseline in HDL-C at Month 12

Time frame:: Baseline, Month 12
Reported as:: Least squares mean · percentage change

Percent Change From Baseline in HDL-C at Month 12
percentage change	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
Percent Change From Baseline in HDL-C at Month 12	20.61 ± 17.249	61.90 ± 14.462	74.52 ± 15.775

Statistical analysis

Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · ANCOVA · p = 0.0669 (ANCOVA with Pattern-mixture Model) · Ls mean difference: 41.28 · 95% CI -2.88 to 85.44
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · ANCOVA · p = 0.0256 (ANCOVA with Pattern-mixture Model) · Ls mean difference: 53.90 · 95% CI 6.60 to 101.21

SecondaryPercent Change From Baseline in Fasting Triglycerides (TG) at Month 12

Time frame:: Baseline, Month 12
Reported as:: Least squares mean · percentage change

Percent Change From Baseline in Fasting Triglycerides (TG) at Month 12
percentage change	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
Percent Change From Baseline in Fasting Triglycerides (TG) at Month 12	0.72 ± 15.962	-61.50 ± 14.334	-45.38 ± 14.542

Statistical analysis

Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · ANCOVA · p = 0.0036 (ANCOVA with Pattern-mixture Model) · Ls mean difference: -62.22 · 95% CI -104.11 to -20.32
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · ANCOVA · p = 0.0338 (ANCOVA with Pattern-mixture Model) · Ls mean difference: -46.10 · 95% CI -88.65 to -3.54

SecondaryPercentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 10

Time frame:: Month 10
Reported as:: Number · percentage of participants

Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 10
percentage of participants	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
<500 mg/dL (<5.6 mmol/L)	5.3	50.0	45.5
<880 mg/dL (<9.9 mmol/L)	21.1	75.0	54.5
<1000 mg/dL (<11.3 mmol/L)	31.6	83.3	68.2

Statistical analysis

Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · Regression, Logistic · p = 0.0066 (The odds ratio, corresponding 95% CI and p-value are based on a logistic regression model with treatment group, and baseline triglyceride level as a covariate.) · Odds ratio (or): 21.120 · 95% CI 2.343 to 190.405
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · Regression, Logistic · p = 0.0106 (The odds ratio, corresponding 95% CI and p-value are based on a logistic regression model with treatment group, and baseline triglyceride level as a covariate.) · Odds ratio (or): 17.953 · 95% CI 1.960 to 164.414
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · Regression, Logistic · p = 0.0005 (The odds ratio, corresponding 95% CI and p-value are based on a logistic regression model with treatment group, and baseline triglyceride level as a covariate.) · Odds ratio (or): 15.448 · 95% CI 3.280 to 72.762
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · Regression, Logistic · p = 0.0194 (The odds ratio, corresponding 95% CI and p-value are based on a logistic regression model with treatment group, and baseline triglyceride level as a covariate.) · Odds ratio (or): 5.708 · 95% CI 1.325 to 24.596
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · Regression, Logistic · p = 0.0005 (The odds ratio, corresponding 95% CI and p-value are based on a logistic regression model with treatment group, and baseline triglyceride level as a covariate.) · Odds ratio (or): 20.838 · 95% CI 3.737 to 116.182
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · Regression, Logistic · p = 0.0086 (The odds ratio, corresponding 95% CI and p-value are based on a logistic regression model with treatment group, and baseline triglyceride level as a covariate.) · Odds ratio (or): 7.640 · 95% CI 1.676 to 34.830

SecondaryPercentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 12

Time frame:: Month 12
Reported as:: Number · percentage of participants

Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 12
percentage of participants	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
<500 mg/dL (<5.6 mmol/L)	10.5	45.8	40.9
<880 mg/dL (<9.9 mmol/L)	26.3	75.0	59.1
<1000 mg/dL (<11.3 mmol/L)	26.3	75.0	63.6

Statistical analysis

Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · Regression, Logistic · p = 0.0131 (The odds ratio, corresponding 95% CI and p-value are based on a logistic regression model with treatment group, and baseline triglyceride level as a covariate.) · Odds ratio (or): 9.097 · 95% CI 1.589 to 52.074
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · Regression, Logistic · p = 0.0257 (The odds ratio, corresponding 95% CI and p-value are based on a logistic regression model with treatment group, and baseline triglyceride level as a covariate.) · Odds ratio (or): 7.435 · 95% CI 1.275 to 43.360
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · Regression, Logistic · p = 0.0014 (The odds ratio, corresponding 95% CI and p-value are based on a logistic regression model with treatment group, and baseline triglyceride level as a covariate.) · Odds ratio (or): 11.195 · 95% CI 2.553 to 49.096
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · Regression, Logistic · p = 0.0223 (The odds ratio, corresponding 95% CI and p-value are based on a logistic regression model with treatment group, and baseline triglyceride level as a covariate.) · Odds ratio (or): 5.166 · 95% CI 1.263 to 21.131
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · Regression, Logistic · p = 0.0013 (The odds ratio, corresponding 95% CI and p-value are based on a logistic regression model with treatment group, and baseline triglyceride level as a covariate.) · Odds ratio (or): 11.623 · 95% CI 2.612 to 51.726
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · Regression, Logistic · p = 0.0102 (The odds ratio, corresponding 95% CI and p-value are based on a logistic regression model with treatment group, and baseline triglyceride level as a covariate.) · Odds ratio (or): 6.640 · 95% CI 1.568 to 28.119

SecondaryPercentage of Participants Achieving ≥40% and ≥70% Reduction From Baseline in Fasting TG at Month 10

Time frame:: Baseline, Month 10
Reported as:: Number · percentage of participants

Percentage of Participants Achieving ≥40% and ≥70% Reduction From Baseline in Fasting TG at Month 10
percentage of participants	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
≥40% reduction from baseline fasting triglycerides	26.3	95.8	86.4
≥70% reduction from baseline fasting triglycerides	10.5	66.7	54.5

Statistical analysis

Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · Regression, Logistic · p = 0.0003 (The odds ratio, corresponding 95% CI and p-value are based on a logistic regression model with treatment group, and baseline triglyceride level as a covariate.) · Odds ratio (or): 65.020 · 95% CI 6.791 to 622.535
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · Regression, Logistic · p = 0.0005 (The odds ratio, corresponding 95% CI and p-value are based on a logistic regression model with treatment group, and baseline triglyceride level as a covariate.) · Odds ratio (or): 17.440 · 95% CI 3.518 to 86.446
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 25 mg · Regression, Logistic · p = 0.0009 (The odds ratio, corresponding 95% CI and p-value are based on a logistic regression model with treatment group, and baseline triglyceride level as a covariate.) · Odds ratio (or): 18.262 · 95% CI 3.302 to 100.991
Placebo (Pooled) vs ARO-APOC3 (Plozasiran) 50 mg · Regression, Logistic · p = 0.0057 (The odds ratio, corresponding 95% CI and p-value are based on a logistic regression model with treatment group, and baseline triglyceride level as a covariate.) · Odds ratio (or): 11.109 · 95% CI 2.015 to 61.235

SecondaryChange From Baseline in Fasting TG Over Time

Time frame:: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Reported as:: Mean · mg/dL

Change From Baseline in Fasting TG Over Time
mg/dL	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
Change at Month 1	180.81 ± 247.835	-1898.79 ± 205.603	-1759.36 ± 277.758
Change at Month 2	-203.67 ± 195.740	-1519.38 ± 203.397	-1481.57 ± 218.704
Change at Month 3	392.98 ± 320.073	-1177.43 ± 212.134	-1478.94 ± 276.681
Change at Month 4	-248.76 ± 198.553	-1521.25 ± 291.471	-1810.31 ± 245.695
Change at Month 5	-213.43 ± 216.851	-1613.90 ± 176.086	-1689.31 ± 330.096
Change at Month 6	-276.07 ± 205.490	-1566.97 ± 201.610	-1325.13 ± 215.809
Change at Month 7	324.98 ± 319.233	-1842.65 ± 210.671	-1691.87 ± 285.252
Change at Month 8	188.62 ± 271.286	-1537.57 ± 190.088	-1133.96 ± 279.984
Change at Month 9	-119.48 ± 226.547	-1413.87 ± 232.426	-1650.75 ± 329.600
Change at Month 10	-248.35 ± 233.539	-1819.82 ± 227.632	-1740.20 ± 293.567
Change at Month 11	173.14 ± 336.713	-1810.57 ± 296.726	-1507.08 ± 203.964
Change at Month 12	-50.32 ± 273.674	-1637.18 ± 274.479	-1485.30 ± 339.662

SecondaryPercent Change From Baseline in Fasting TG Over Time

Time frame:: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Reported as:: Mean · percentage change

Percent Change From Baseline in Fasting TG Over Time
percentage change	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
Percent Change at Month 1	13.21 ± 14.003	-81.43 ± 2.854	-68.21 ± 5.390
Percent Change at Month 2	-7.30 ± 10.375	-69.33 ± 5.119	-62.96 ± 5.940
Percent Change at Month 3	14.66 ± 12.028	-57.13 ± 7.424	-60.94 ± 6.761
Percent Change at Month 4	-1.74 ± 8.861	-68.27 ± 8.795	-71.91 ± 5.076
Percent Change at Month 5	-9.23 ± 9.561	-71.96 ± 5.052	-60.41 ± 10.796
Percent Change at Month 6	-6.18 ± 12.679	-68.08 ± 4.884	-56.30 ± 6.317
Percent Change at Month 7	21.45 ± 15.235	-77.44 ± 4.082	-65.88 ± 5.863
Percent Change at Month 8	14.98 ± 13.745	-68.35 ± 4.805	-47.77 ± 11.563
Percent Change at Month 9	4.08 ± 12.059	-55.32 ± 8.363	-62.72 ± 7.369
Percent Change at Month 10	-8.74 ± 11.466	-74.45 ± 4.135	-66.53 ± 5.951
Percent Change at Month 11	10.40 ± 16.139	-68.39 ± 6.776	-63.83 ± 6.143
Percent Change at Month 12	0.93 ± 14.858	-67.69 ± 5.985	-50.60 ± 14.269

SecondaryNumber of Participants With Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs; Randomized Period)

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.

Time frame:: From first dose of study drug through Month 12 (Randomized Period)
Reported as:: Count of participants · Participants

Number of Participants With Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs; Randomized Period)
Participants	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
All TEAEs	20	23	20
Treatment-related TEAEs	6	7	8
Serious TEAEs	7	5	2
TEAEs leading to study drug discontinuation	0	2	1
TEAEs leading to study termination	0	2	1
TEAEs of clinical interest	1	4	2
Any TEAE by maximum severity: Mild	5	13	13
Any TEAE by maximum severity: Moderate	10	7	4
Any TEAE by maximum severity: Severe	5	2	3
Any TEAE by maximum severity: Life Threatening	0	1	0
Any TEAE by maximum severity: Death	0	0	0

SecondaryNumber of Participants With Treatment-Emergent AEs and/or SAEs (Open-Label Period)

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

Results for this outcome have not been posted.

Adverse events

Collected over Screening through Month 12 (Randomized Period). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Placebo (Pooled)	0/25 (0%)	7/25 (28%)	17/25 (68%)
ARO-APOC3 (Plozasiran) 25 mg	0/26 (0%)	5/26 (19.2%)	21/26 (80.8%)
ARO-APOC3 (Plozasiran) 50 mg	0/24 (0%)	2/24 (8.3%)	18/24 (75%)

Most frequent serious events

Showing 10 of 14

Most frequent serious events
Event	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
Pancreatitis acuteGastrointestinal disorders	3/25	2/26	0/24
Pancreatitis relapsingGastrointestinal disorders	3/25	0/26	1/24
CellulitisInfections and infestations	0/25	0/26	1/24
Tooth abscessInfections and infestations	0/25	0/26	1/24
Laryngeal oedemaRespiratory, thoracic and mediastinal disorders	0/25	0/26	1/24
Coronary artery stenosisCardiac disorders	1/25	0/26	0/24
Large intestine polypGastrointestinal disorders	1/25	0/26	0/24
PancreatitisGastrointestinal disorders	1/25	0/26	0/24
Anaphylactic shockImmune system disorders	1/25	0/26	0/24
ProstatitisReproductive system and breast disorders	1/25	0/26	0/24

Most frequent other events

Showing 10 of 33

Most frequent other events
Event	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg
Abdominal painGastrointestinal disorders	7/25	7/26	7/24
COVID-19Infections and infestations	1/25	5/26	7/24
HeadacheNervous system disorders	2/25	3/26	5/24
NasopharyngitisInfections and infestations	4/25	5/26	2/24
DiarrhoeaGastrointestinal disorders	2/25	1/26	4/24
NauseaGastrointestinal disorders	2/25	4/26	3/24
Abdominal discomfortGastrointestinal disorders	0/25	0/26	3/24
Glycosylated haemoglobin increasedInvestigations	0/25	3/26	3/24
PalpitationsCardiac disorders	0/25	3/26	0/24
Upper respiratory tract infectionInfections and infestations	2/25	3/26	2/24

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg	Total
Mean	47.4 ± 13.93	47.9 ± 14.41	42.6 ± 10.85	46.0 ± 13.24

Sex: Female, Male
Sex: Female, Male(Participants)	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg	Total
Female	11	14	13	38
Male	14	12	11	37

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg	Total
Hispanic or Latino	1	0	1	2
Not Hispanic or Latino	24	26	22	72
Unknown or Not Reported	0	0	1	1

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg	Total
White	19	19	17	55
American Indian or Alaska Native	0	0	1	1
Asian	4	7	5	16
Other, not specified	2	0	1	3

Triglycerides
Triglycerides(mg/dL)	Placebo (Pooled)	ARO-APOC3 (Plozasiran) 25 mg	ARO-APOC3 (Plozasiran) 50 mg	Total
Mean	2271.91 ± 1141.426	2349.53 ± 1374.542	2491.45 ± 1523.200	2369.07 ± 1337.965

Study locations

58 sites

Clinical Site 1
Boca Raton, Florida 33434, United States
Clinical Site 2
Suwanee, Georgia 30024, United States
Clinical Site 3
Indianapolis, Indiana 46290, United States
Clinical Site 4
Elkridge, Maryland 21075, United States
Clinical Site 5
St Louis, Missouri 63110, United States
Clinical Site 7
New York, New York 10016, United States
Clinical Site 6
New York, New York 10029, United States
Clinical Site 8
Austin, Texas 78731, United States
Clinical Site 9
Norfolk, Virginia 23510, United States
Clinical Site 10
Córdoba, X5003DCE, Argentina
Clinical Site 11
Formosa, 3600, Argentina
Clinical Site 14
Camperdown, New South Wales 2050, Australia
Clinical Site 15
St Leonards, New South Wales 2065, Australia
Clinical Site 16
Melbourne, Victoria 3004, Australia
Clinical Site 12
Melbourne, 3081, Australia
Clinical Site 13
Nedlands, 6009, Australia
Clinical Site 17
Graz, 8036, Austria
Clinical Site 18
Edegem, 2650, Belgium
Clinical Site 19
Ghent, 9000, Belgium
Clinical Site 20
Leuven, 3000, Belgium
Clinical Site 21
Liège, 4000, Belgium
Clinical Site 22
London, Ontario N6A 5B7, Canada
Clinical Site 23
Toronto, Ontario M5G 2C4, Canada
Clinical Site 24
Chicoutimi, Quebec G7H 7K9, Canada
Clinical Site 25
Montreal, Quebec H2W 1R7, Canada
Clinical Site 26
Québec, Quebec G1V 4W2, Canada
Clinical Site 27
Zagreb, 10000, Croatia
Clinical Site 29
Marseille, Cedez 05 13385, France
Clinical Site 28
Paris, 75013, France
Clinical Site 30
Jena, 7740, Germany
Clinical Site 31
Leipzig, 4103, Germany
Clinical Site 32
Galway, H91 YR71, Ireland
Clinical Site 33
Jerusalem, 9112001, Israel
Clinical Site 34
Chiba, 260-8677, Japan
Clinical Site 35
Ishikawa, 920-8641, Japan
Clinical Site 36
Osaka, 598-0048, Japan
Clinical Site 37
Tochigi, 329-0498, Japan
Clinical Site 38
Tokyo, 113-8655, Japan
Clinical Site 39
Tokyo, Japan
Clinical Site 41
Tlalpan, Mexico DF 14000, Mexico
Clinical Site 42
Cuernavaca, Morelos 62250, Mexico
Clinical Site 40
Mexico City, 11650, Mexico
Clinical Site 44
Auckland, 1010, New Zealand
Clinical Site 43
Auckland, 2025, New Zealand
Clinical Site 45
Christchurch, 8011, New Zealand
Clinical Site 46
Muscat, Oman
Clinical Site 47
Lodz, 93-338, Poland
Clinical Site 48
Belgrade, 11000, Serbia
Clinical Site 49
Niš, 18000, Serbia
Clinical Site 50
Singapore, 119074, Singapore
Clinical Site 51
Gwangju, 61469, South Korea
Clinical Site 52
Seoul, 03080, South Korea
Clinical Site 53
A Coruña, 15001, Spain
Clinical Site 54
Granada, 18012, Spain
Clinical Site 55
Madrid, 28007, Spain
Clinical Site 56
Santiago de Compostela, 15706, Spain
Clinical Site 58
Melikgazi, Kayseri 38030, Turkey (Türkiye)
Clinical Site 57
Izmir, 35100, Turkey (Türkiye)

References and documents

Publications

Loomba R, de-Madaria E, Afghani E, Singh VK, Leeper NJ. Clinical Trial: Plozasiran Prevents Recurrent Pancreatitis in Adults With Very Severe Hypertriglyceridemia-Results of a Post Hoc Analysis of the Phase 3 PALISADE Study. Aliment Pharmacol Ther. 2026 May;63(9):1236-1245. doi: 10.1111/apt.70623. Epub 2026 Apr 1. PubMed 41923352 ↗
Watts GF, Rosenson RS, Hegele RA, Goldberg IJ, Gallo A, Mertens A, Baass A, Zhou R, Muhsin M, Hellawell J, Leeper NJ, Gaudet D; PALISADE Study Group. Plozasiran for Managing Persistent Chylomicronemia and Pancreatitis Risk. N Engl J Med. 2025 Jan 9;392(2):127-137. doi: 10.1056/NEJMoa2409368. Epub 2024 Sep 2. PubMed 39225259 ↗

Study documents

Study protocol · Nov 8, 2024
Statistical analysis plan · May 6, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Registry details

Key details

Study ID: NCT05089084
Lead sponsor: Arrowhead Pharmaceuticals
Responsible party: Sponsor
First posted: Oct 22, 2021
Start date: Dec 14, 2021
Primary completion: Apr 29, 2024
Completion: Apr 21, 2026
Results posted: Feb 4, 2026
Last update: Jun 5, 2026

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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

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