Familial ChylomicronemiaPhase 3PALISADENCT05089084
Study of ARO-APOC3 (Plozasiran) in Adults With Familial Chylomicronemia Syndrome (FCS)
A Phase 3 study testing Plozasiran in people with Familial Chylomicronemia, run by Arrowhead Pharmaceuticals at 58 sites in 21 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Familial Chylomicronemia
- What is being tested?
- Plozasiran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 58 sitesin 21 countries
- Study dates
- 14 Dec 2021to 21 Apr 2026
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
58 sites in 21 countries.
58 sites in 21 countries
United States9 sites
Clinical Site 8
Austin, Texas, 78731
Clinical Site 1
Boca Raton, Florida, 33434
Clinical Site 4
Elkridge, Maryland, 21075
Clinical Site 3
Indianapolis, Indiana, 46290
Clinical Site 7
New York, New York, 10016
Clinical Site 6
New York, New York, 10029
Clinical Site 9
Norfolk, Virginia, 23510
Clinical Site 5
St Louis, Missouri, 63110
Clinical Site 2
Suwanee, Georgia, 30024
Japan6 sites
Clinical Site 34
Chiba, 260-8677
Clinical Site 35
Ishikawa, 920-8641
Clinical Site 36
Osaka, 598-0048
Clinical Site 37
Tochigi, 329-0498
Clinical Site 38
Tokyo, 113-8655
Clinical Site 39
Tokyo
Australia5 sites
Clinical Site 14
Camperdown, New South Wales, 2050
Clinical Site 16
Melbourne, Victoria, 3004
Clinical Site 12
Melbourne, 3081
Clinical Site 13
Nedlands, 6009
Clinical Site 15
St Leonards, New South Wales, 2065
Canada5 sites
Clinical Site 24
Chicoutimi, Quebec, G7H 7K9
Clinical Site 22
London, Ontario, N6A 5B7
Clinical Site 25
Montreal, Quebec, H2W 1R7
Clinical Site 26
Québec, Quebec, G1V 4W2
Clinical Site 23
Toronto, Ontario, M5G 2C4
Belgium4 sites
Clinical Site 18
Edegem, 2650
Clinical Site 19
Ghent, 9000
Clinical Site 20
Leuven, 3000
Clinical Site 21
Liège, 4000
Spain4 sites
Clinical Site 53
A Coruña, 15001
Clinical Site 54
Granada, 18012
Clinical Site 55
Madrid, 28007
Clinical Site 56
Santiago de Compostela, 15706
Mexico3 sites
Clinical Site 42
Cuernavaca, Morelos, 62250
Clinical Site 40
Mexico City, 11650
Clinical Site 41
Tlalpan, Mexico DF, 14000
New Zealand3 sites
Clinical Site 44
Auckland, 1010
Clinical Site 43
Auckland, 2025
Clinical Site 45
Christchurch, 8011
Argentina2 sites
Clinical Site 10
Córdoba, X5003DCE
Clinical Site 11
Formosa, 3600
France2 sites
Clinical Site 29
Marseille, Cedez 05, 13385
Clinical Site 28
Paris, 75013
South Korea2 sites
Clinical Site 51
Gwangju, 61469
Clinical Site 52
Seoul, 03080
Turkey (Türkiye)2 sites
Clinical Site 57
Izmir, 35100
Clinical Site 58
Melikgazi, Kayseri, 38030
About this study
Official title: 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.
- Conditions
- Familial Chylomicronemia
- Being tested
- Plozasiran, Placebo
- Medical subject headings
- Hyperlipoproteinemia Type I
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlozasiranDrug
Also called ARO-APOC3
ARO-APOC3 subcutaneous (SC) injection
PlaceboDrug
sterile normal saline (0.9% NaCl) SC injection
| Study group | Role | What they receive |
|---|---|---|
| ARO-APOC3 (Plozasiran) 25 mg | Experimental | 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. Receives: Drug: Plozasiran |
| Placebo for ARO-APOC3 (Plozasiran) 25 mg | Placebo comparator | 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. Receives: Drug: Plozasiran; Drug: Placebo |
| ARO-APOC3 (Plozasiran) 50 mg | Experimental | 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. Receives: Drug: Plozasiran |
| Placebo for ARO-APOC3 (Plozasiran) 50 mg | Placebo comparator | 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. Receives: Drug: Plozasiran; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline at Month 10 in Fasting Triglycerides (TG)
Measured: Baseline, Month 10
Secondary outcomes (17)
Percent Change From Baseline in Fasting TG at Month 10 and Month 12 (Averaged)
Measured: Baseline, Month 10, Month 12
Percent Change From Baseline in Apolipoprotein C-III (APOC3) at Month 10
Measured: Baseline, Month 10
Percent Change From Baseline in Fasting APOC3 at Month 12
Measured: 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.
Measured: 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.
Measured: 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
Measured: Baseline, Month 10
Percent Change From Baseline in Non-HDL-C at Month 12
Measured: Baseline, Month 12
Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Month 10
Measured: Baseline, Month 10
Percent Change From Baseline in HDL-C at Month 12
Measured: Baseline, Month 12
Percent Change From Baseline in Fasting Triglycerides (TG) at Month 12
Measured: Baseline, Month 12
Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 10
Measured: Month 10
Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 12
Measured: Month 12
Percentage of Participants Achieving ≥40% and ≥70% Reduction From Baseline in Fasting TG at Month 10
Measured: Baseline, Month 10
Change From Baseline in Fasting TG Over Time
Measured: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Percent Change From Baseline in Fasting TG Over Time
Measured: 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.
Measured: 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.
Measured: From first dose of open-label study drug through Month 36 (Open-Label Period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2021
- Study start14 Dec 2021
- Primary completion29 Apr 2024
- Study completion21 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Familial ChylomicronemiaStudies of the same condition, open and under way.
- More trials run by Arrowhead PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arrowhead Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05089084
- Sponsor's protocol ID
- AROAPOC3-3001
- Acronym
- PALISADE
- Status last verified
- May 2026
- First submitted
- 11 Oct 2021
- Last updated
- 5 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
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 41923352Watts 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