Study of Plozasiran (ARO-APOC3) in Adults With Mixed Dyslipidemia

NCT04998201 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: AROAPOC3-20022021-000688-57
• Study Type: interventional
• Target: 353
• Locations: 6 countries
• Sites: 30

Brief Summary

Participants who have met all protocol eligibility criteria will be randomly assigned to treatment (ARO-APOC3 or placebo) in a double-blind fashion and will be evaluated for safety and efficacy over 48 weeks. Participants will be counseled to remain on a specified diet throughout the study, as recommended by the Investigator in accordance with local standards of care. After week 48, participants will be eligible and invited to consent and continue in an open-label extension study. All placebo participants who opt to continue will switch to active drug (ARO-APOC3) during the extension study.

Conditions

Mixed Dyslipidemia

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline at Week 24 in Fasting TG

  Least square (LS) mean and standard error (SE) were calculated using mixed model repeated measures (MMRM) which included treatment arm, study visit, and baseline value as model terms and treatment by visit and treatment by baseline as interaction terms.

  Baseline, Week 24

Secondary Outcomes (12)

• Percent Change From Baseline Over Time Through Week 48 in Fasting TG

  Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)

• Percent Change From Baseline at Week 24 in Apolipoprotein (Apo)C-III

  Baseline, Week 24

• Percent Change From Baseline Over Time Through Week 48 in ApoC-III

  Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/ET

• Percent Change From Baseline at Week 24 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C)

  Baseline, Week 24

• Percent Change From Baseline Over Time Through Week 48 in Fasting Non-HDL-C

  Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/ET

Study Arms (5)

ARO-APOC3 10 mg Q12W

EXPERIMENTAL

ARO-APOC3 10 milligrams (mg) subcutaneous (SC) injection on Day 1 and Week 12 (Q12W) for a total of 2 injections

Drug: ARO-APOC3

ARO-APOC3 25 mg Q12W

EXPERIMENTAL

ARO-APOC3 25 mg SC injection on Day 1 and Week 12 (Q12W) for a total of 2 injections

Drug: ARO-APOC3

ARO-APOC3 50 mg Q12W

EXPERIMENTAL

ARO-APOC3 50 mg SC injection on Day 1 and Week 12 (Q12W) for a total of 2 injections

Drug: ARO-APOC3

ARO-APOC3 50 mg Q24W

EXPERIMENTAL

ARO-APOC3 50 mg SC injection on Day 1 and Week 24 (Q24W) for a total of 2 injections

Drug: ARO-APOC3

Placebo

PLACEBO COMPARATOR

Volume-matched placebo SC injection on Day 1 and Week 12 for a total of 2 injections

Drug: Placebo

Interventions

Placebo DRUG

Sterile Normal Saline (0.9% NaCl)

Placebo

ARO-APOC3 DRUG

ARO-APOC3 Injection

Also known as: Plozasiran

ARO-APOC3 10 mg Q12W; ARO-APOC3 25 mg Q12W; ARO-APOC3 50 mg Q12W; ARO-APOC3 50 mg Q24W

Eligibility Criteria

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

You may qualify if:

• Based on medical history, prior evidence of triglycerides (TG) ≥ 150 milligrams (mg)/deciliter (dL) and ≤ 499 mg/dL
• Fasting levels at Screening of non-high-density lipoprotein cholesterol (non-HDL-C) ≥ 100 mg/dL or low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dL after at least 2 weeks of stable diet and 4 weeks on stable optimal statin therapy
• Mean fasting TG ≥ 150 mg/dL and ≤ 499 mg/dL during Screening collected at two separate and consecutive visits and at least 7 days apart and not more than 17 days apart
• Willing to follow diet counseling as per Investigator judgment 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 and females must not donate eggs 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
• Willing to provide written informed consent and to comply with study requirements

You may not qualify if:

• Current use or use within 365 days from Day 1 of any hepatocyte targeted short interfering RNA oligonucleotides (siRNA) or antisense oligonucleotide molecule
• Active pancreatitis within 12 weeks prior to Day 1
• Any planned bariatric surgery or similar procedures to induce weight loss from consent through end of study
• Acute coronary syndrome event within 24 weeks of Day 1
• History of major surgery within 12 weeks of Day 1 or planned major surgery during the study
• Planned coronary intervention (such as, stent placement or heart bypass) during the study
• New York Heart Association (NYHA) Class II, III or IV heart failure or last known ejection fraction of \<30%
• Uncontrolled hypertension
• Known history of human immunodeficiency virus (HIV) infection, seropositive for Hepatitis B virus (HBV), seropositive for Hepatitis C virus (HCV)
• Uncontrolled hypothyroidism or hyperthyroidism
• Hemorrhagic stroke within 24 weeks of Day 1
• History of bleeding diathesis or coagulopathy
• Current diagnosis of nephrotic syndrome
• Systemic use of corticosteroids or anabolic steroids within 4 weeks prior to Day 1 or planned use during the study
• Malignancy within the last 2 years prior to date of consent requiring systemic treatment (some exceptions apply)

Sponsors & Collaborators

• Arrowhead Pharmaceuticals: lead

Study Sites (30)

Research Site 3

Beverly Hills, California, 90211, United States

Location

Research Site 8

Northridge, California, 91325, United States

Location

Research Site 2

Boca Raton, Florida, 33434, United States

Location

Research Site 1

Fort Lauderdale, Florida, 33308, United States

Location

Research Site 14

Miami Springs, Florida, 33166, United States

Location

Research Site 5

Pembroke Pines, Florida, 33024, United States

Location

Research Site 18

Dunwoody, Georgia, 30338, United States

Location

Research Site 31

Las Vegas, Nevada, 89121, United States

Location

Research Site 17

New Windsor, New York, 12553, United States

Location

Research Site 12

Dayton, Ohio, 45419, United States

Location

Research Site 4

Franklin, Ohio, 45005, United States

Location

Research Site 7

Greenville, South Carolina, 29607, United States

Location

Research Site 6

Houston, Texas, 77002, United States

Location

Research Site 32

Houston, Texas, 77030, United States

Location

Research Site 13

San Antonio, Texas, 78249, United States

Location

Research Site 30

Morayfield, Queensland, 4506, Australia

Location

Research Site 29

Adelaide, South Australia, 5000, Australia

Location

Research Site 19

Clayton, Victoria, 3168, Australia

Location

Research Site 27

Joondalup, Western Australia, 6027, Australia

Location

Research Site 15

Concord, Ontario, L4K 4M2, Canada

Location

Research Site 10

Montreal, Quebec, H2W2T2, Canada

Location

Research Site 20

Balatonfüred, H-8230, Hungary

Location

Research Site 21

Debrecen, H-4032, Hungary

Location

Research Site 22

Nyíregyháza, H-4405, Hungary

Location

Research Site 11

Auckland, 2025, New Zealand

Location

Research Site 16

Christchurch, 8013, New Zealand

Location

Research Site 28

Lodz, 93-338, Poland

Location

Research Site 24

Lodz, 94-048, Poland

Location

Research Site 25

Poznan, 61-655, Poland

Location

Research Site 26

Rzeszów, 35-055, Poland

Location

Related Publications (1)

• Ballantyne CM, Vasas S, Azizad M, Clifton P, Rosenson RS, Chang T, Melquist S, Zhou R, Mushin M, Leeper NJ, Hellawell J, Gaudet D. Plozasiran, an RNA Interference Agent Targeting APOC3, for Mixed Hyperlipidemia. N Engl J Med. 2024 Sep 12;391(10):899-912. doi: 10.1056/NEJMoa2404143. Epub 2024 May 28.

  PMID: 38804517 DERIVED

MeSH Terms

Interventions

plozasiran

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 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2021
• First Posted: August 10, 2021
• Study Start: September 28, 2021
• Primary Completion: February 10, 2023
• Study Completion: August 14, 2023
• Last Updated: April 14, 2026
• Results First Posted: February 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4); US (15); HU (3); NZ (2); PL (4); CA (2)