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

A Phase 3 Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults With Familial Chylomicronemia Syndrome

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Familial Chylomicronemia
• Intervention / Treatment: Drug: Plozasiran; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; ARO-APOC3 subcutaneous (SC) injection; Other Names: ARO-APOC3
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; ARO-APOC3 subcutaneous (SC) injection; Other Names: ARO-APOC3; Drug: Placebo; sterile normal saline (0.9% NaCl) SC injection
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; ARO-APOC3 subcutaneous (SC) injection; Other Names: ARO-APOC3
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; ARO-APOC3 subcutaneous (SC) injection; Other Names: ARO-APOC3; Drug: Placebo; sterile normal saline (0.9% NaCl) SC injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline at Month 10 in Fasting Triglycerides (TG)	Baseline, Month 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Fasting TG at Month 10 and Month 12 (Averaged)		Baseline, Month 10, Month 12
Percent Change From Baseline in Apolipoprotein C-III (APOC3) at Month 10		Baseline, Month 10
Percent Change From Baseline in Fasting APOC3 at Month 12		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: Abdominal pain consistent with acute pancreatitis (acute onset of a persistent, severe, epigastric pain often radiating to the back); Serum lipase activity (or amylase activity) ≥3 times the upper limit of normal (×ULN); Characteristic findings of acute pancreatitis on contrast-enhanced computed tomography (CECT), magnetic resonance imaging (MRI), or transabdominal ultrasonography.	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: Abdominal pain consistent with acute pancreatitis (acute onset of a persistent, severe, epigastric pain often radiating to the back); Serum lipase activity (or amylase activity) ≥3 times the upper limit of normal (×ULN); Characteristic findings of acute pancreatitis on contrast-enhanced computed tomography (CECT), magnetic resonance imaging (MRI), or transabdominal ultrasonography.	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		Baseline, Month 10
Percent Change From Baseline in Non-HDL-C at Month 12		Baseline, Month 12
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Month 10		Baseline, Month 10
Percent Change From Baseline in HDL-C at Month 12		Baseline, Month 12
Percent Change From Baseline in Fasting Triglycerides (TG) at Month 12		Baseline, Month 12
Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 10		Month 10
Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 12		Month 12
Percentage of Participants Achieving ≥40% and ≥70% Reduction From Baseline in Fasting TG at Month 10		Baseline, Month 10
Change From Baseline in Fasting TG Over Time		Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Percent Change From Baseline in Fasting TG Over Time		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.	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.	From first dose of open-label study drug through Month 36 (Open-Label Period)

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Helpful Links

• Expanded access record

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2021
• Primary Completion (Actual): April 29, 2024
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: October 11, 2021
• First Submitted That Met QC Criteria: October 11, 2021
• First Posted (Actual): October 22, 2021

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hyperlipoproteinemia Type I; plozasiran
• Other Study ID Numbers: AROAPOC3-3001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No