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

NCT05089084 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 1 other identifier: AROAPOC3-3001
• Study Type: interventional
• Target: 75
• Locations: 20 countries
• Sites: 57

Brief 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

Familial Chylomicronemia

Outcome Measures

Primary Outcomes (1)

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

  Baseline, Month 10

Secondary Outcomes (17)

• 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)

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

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

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

Study Arms (4)

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.

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.

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.

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.

Drug: Plozasiran; Drug: Placebo

Interventions

Plozasiran DRUG

ARO-APOC3 subcutaneous (SC) injection

Also known as: ARO-APOC3

ARO-APOC3 (Plozasiran) 25 mg; ARO-APOC3 (Plozasiran) 50 mg; Placebo for ARO-APOC3 (Plozasiran) 25 mg; Placebo for ARO-APOC3 (Plozasiran) 50 mg

Placebo DRUG

sterile normal saline (0.9% NaCl) SC injection

Placebo for ARO-APOC3 (Plozasiran) 25 mg; Placebo for ARO-APOC3 (Plozasiran) 50 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Arrowhead Pharmaceuticals: lead

Study Sites (58)

Clinical Site 1

Boca Raton, Florida, 33434, United States

Location

Clinical Site 2

Suwanee, Georgia, 30024, United States

Location

Clinical Site 3

Indianapolis, Indiana, 46290, United States

Location

Clinical Site 4

Elkridge, Maryland, 21075, United States

Location

Clinical Site 5

St Louis, Missouri, 63110, United States

Location

Clinical Site 7

New York, New York, 10016, United States

Location

Clinical Site 6

New York, New York, 10029, United States

Location

Clinical Site 8

Austin, Texas, 78731, United States

Location

Clinical Site 9

Norfolk, Virginia, 23510, United States

Location

Clinical Site 10

Córdoba, X5003DCE, Argentina

Location

Clinical Site 11

Formosa, 3600, Argentina

Location

Clinical Site 14

Camperdown, New South Wales, 2050, Australia

Location

Clinical Site 15

St Leonards, New South Wales, 2065, Australia

Location

Clinical Site 16

Melbourne, Victoria, 3004, Australia

Location

Clinical Site 12

Melbourne, 3081, Australia

Location

Clinical Site 13

Nedlands, 6009, Australia

Location

Clinical Site 17

Graz, 8036, Austria

Location

Clinical Site 18

Edegem, 2650, Belgium

Location

Clinical Site 19

Ghent, 9000, Belgium

Location

Clinical Site 20

Leuven, 3000, Belgium

Location

Clinical Site 21

Liège, 4000, Belgium

Location

Clinical Site 22

London, Ontario, N6A 5B7, Canada

Location

Clinical Site 23

Toronto, Ontario, M5G 2C4, Canada

Location

Clinical Site 24

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Clinical Site 25

Montreal, Quebec, H2W 1R7, Canada

Location

Clinical Site 26

Québec, Quebec, G1V 4W2, Canada

Location

Clinical Site 27

Zagreb, 10000, Croatia

Location

Clinical Site 29

Marseille, Cedez 05, 13385, France

Location

Clinical Site 28

Paris, 75013, France

Location

Clinical Site 30

Jena, 7740, Germany

Location

Clinical Site 31

Leipzig, 4103, Germany

Location

Clinical Site 32

Galway, H91 YR71, Ireland

Location

Clinical Site 33

Jerusalem, 9112001, Israel

Location

Clinical Site 34

Chiba, 260-8677, Japan

Location

Clinical Site 35

Ishikawa, 920-8641, Japan

Location

Clinical Site 36

Osaka, 598-0048, Japan

Location

Clinical Site 37

Tochigi, 329-0498, Japan

Location

Clinical Site 38

Tokyo, 113-8655, Japan

Location

Clinical Site 39

Tokyo, Japan

Location

Clinical Site 41

Tlalpan, Mexico DF, 14000, Mexico

Location

Clinical Site 42

Cuernavaca, Morelos, 62250, Mexico

Location

Clinical Site 40

Mexico City, 11650, Mexico

Location

Clinical Site 44

Auckland, 1010, New Zealand

Location

Clinical Site 43

Auckland, 2025, New Zealand

Location

Clinical Site 45

Christchurch, 8011, New Zealand

Location

Clinical Site 46

Muscat, Oman

Location

Clinical Site 47

Lodz, 93-338, Poland

Location

Clinical Site 48

Belgrade, 11000, Serbia

Location

Clinical Site 49

Niš, 18000, Serbia

Location

Clinical Site 50

Singapore, 119074, Singapore

Location

Clinical Site 51

Gwangju, 61469, South Korea

Location

Clinical Site 52

Seoul, 03080, South Korea

Location

Clinical Site 53

A Coruña, 15001, Spain

Location

Clinical Site 54

Granada, 18012, Spain

Location

Clinical Site 55

Madrid, 28007, Spain

Location

Clinical Site 56

Santiago de Compostela, 15706, Spain

Location

Clinical Site 58

Melikgazi, Kayseri, 38030, Turkey (Türkiye)

Location

Clinical Site 57

Izmir, 35100, Turkey (Türkiye)

Location

Related Publications (1)

• 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.

  PMID: 39225259 DERIVED

Related Links

• Expanded access record

MeSH Terms

Conditions

Hyperlipoproteinemia Type I

Interventions

plozasiran

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Chief Operating Officer
• Organization: Arrowhead Pharmaceuticals, Inc.

info@arrowheadpharma.com

1 (626) 304-3400

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 11, 2021
• First Posted: October 22, 2021
• Study Start: December 14, 2021
• Primary Completion: April 29, 2024
• Study Completion: April 1, 2026
• Last Updated: February 4, 2026
• Results First Posted: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

TU (2); OM (1); NZ (3); IL (1); SE (2); AU (5); BE (4); IE (1); SG (1); AR (2); PL (1); US (9); DE (2); ME (3); ES (4); KR (2); CA (5); CR (1); FR (2); JP (6)