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

A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of Plozasiran in Adults With Mixed Dyslipidemia

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.

Study Overview

• Status: Completed
• Conditions: Mixed Dyslipidemia
• Intervention / Treatment: Drug: Placebo; Drug: ARO-APOC3

• Study Type: Interventional
• Enrollment (Actual): 353
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Morayfield, Queensland, Australia, 4506
      • Research Site 30
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Research Site 29
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Research Site 19
  • Western Australia
    • Joondalup, Western Australia, Australia, 6027
      • Research Site 27
• Canada
  • Ontario
    • Concord, Ontario, Canada, L4K 4M2
      • Research Site 15
  • Quebec
    • Montreal, Quebec, Canada, H2W2T2
      • Research Site 10
• Hungary
  • Balatonfüred, Hungary, H-8230
    • Research Site 20
  • Debrecen, Hungary, H-4032
    • Research Site 21
  • Nyíregyháza, Hungary, H-4405
    • Research Site 22
• New Zealand
  • Auckland, New Zealand, 2025
    • Research Site 11
  • Christchurch, New Zealand, 8013
    • Research Site 16
• Poland
  • Lodz, Poland, 93-338
    • Research Site 28
  • Lodz, Poland, 94-048
    • Research Site 24
  • Poznan, Poland, 61-655
    • Research Site 25
  • Rzeszów, Poland, 35-055
    • Research Site 26
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Research Site 3
    • Northridge, California, United States, 91325
      • Research Site 8
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Research Site 2
    • Fort Lauderdale, Florida, United States, 33308
      • Research Site 1
    • Miami Springs, Florida, United States, 33166
      • Research Site 14
    • Pembroke Pines, Florida, United States, 33024
      • Research Site 5
  • Georgia
    • Dunwoody, Georgia, United States, 30338
      • Research Site 18
  • Nevada
    • Las Vegas, Nevada, United States, 89121
      • Research Site 31
  • New York
    • New Windsor, New York, United States, 12553
      • Research Site 17
  • Ohio
    • Dayton, Ohio, United States, 45419
      • Research Site 12
    • Franklin, Ohio, United States, 45005
      • Research Site 4
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Research Site 7
  • Texas
    • Houston, Texas, United States, 77002
      • Research Site 6
    • Houston, Texas, United States, 77030
      • Research Site 32
    • San Antonio, Texas, United States, 78249
      • Research Site 13

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

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

Key Exclusion Criteria:

• 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)

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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARO-APOC3 10 mg Q12W; 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 Injection; Other Names: Plozasiran
Experimental: ARO-APOC3 25 mg Q12W; ARO-APOC3 25 mg SC injection on Day 1 and Week 12 (Q12W) for a total of 2 injections	Drug: ARO-APOC3; ARO-APOC3 Injection; Other Names: Plozasiran
Experimental: ARO-APOC3 50 mg Q12W; ARO-APOC3 50 mg SC injection on Day 1 and Week 12 (Q12W) for a total of 2 injections	Drug: ARO-APOC3; ARO-APOC3 Injection; Other Names: Plozasiran
Experimental: ARO-APOC3 50 mg Q24W; ARO-APOC3 50 mg SC injection on Day 1 and Week 24 (Q24W) for a total of 2 injections	Drug: ARO-APOC3; ARO-APOC3 Injection; Other Names: Plozasiran
Placebo Comparator: Placebo; Volume-matched placebo SC injection on Day 1 and Week 12 for a total of 2 injections	Drug: Placebo; Sterile Normal Saline (0.9% NaCl)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline Over Time Through Week 48 in Fasting TG	LS mean and SE were calculated using 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, 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	LS mean and SE were calculated using 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
Percent Change From Baseline Over Time Through Week 48 in ApoC-III	LS mean and SE were calculated using 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, 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)	LS mean and SE were calculated using 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
Percent Change From Baseline Over Time Through Week 48 in Fasting Non-HDL-C	LS mean and SE were calculated using 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, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/ET
Percent Change From Baseline at Week 24 in Fasting High-Density Lipoprotein Cholesterol (HDL-C)	LS mean and SE were calculated using 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
Percent Change From Baseline Over Time Through Week 48 in Fasting HDL-C	LS mean and SE were calculated using 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, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/ET
Percent Change From Baseline at Week 24 in Fasting Total Apolipoprotein B (ApoB)	LS mean and SE were calculated using 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
Percent Change From Baseline Over Time Through Week 48 in Fasting Total ApoB	LS mean and SE were calculated using 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, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/ET
Percent Change From Baseline at Week 24 in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C)	LS mean and SE were calculated using 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
Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C	LS mean and SE were calculated using 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, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/ET
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence, which did not necessarily have to have a causal relationship with this treatment. A serious AE (SAE) was an AE that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of an existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; or was a medically important event or reaction. TEAEs were AEs that occurred following study drug administration or a pre-existing condition exacerbated following study drug administration.	Up to Week 48

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2021
• Primary Completion (Actual): February 10, 2023
• Study Completion (Actual): August 14, 2023

Study Registration Dates

• First Submitted: August 3, 2021
• First Submitted That Met QC Criteria: August 3, 2021
• First Posted (Actual): August 10, 2021

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; plozasiran
• Other Study ID Numbers: AROAPOC3-2002; 2021-000688-57 (EudraCT Number)

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