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Completed

NCT Number: NCT04998201

Study of Plozasiran (ARO-APOC3) 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.

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Key information

Conditions

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Research Site 30, Morayfield, Queensland, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

ARO-APOC3

Drug

ARO-APOC3 Injection

Other names: Plozasiran

Placebo

Drug

Sterile Normal Saline (0.9% NaCl)

Primary outcomes

  1. Percent Change From Baseline at Week 24 in Fasting TG

    Time frame: Baseline, Week 24

    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.

Secondary outcomes

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

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

    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.

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

    Time frame: Baseline, Week 24

    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.

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

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

    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.

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

    Time frame: Baseline, Week 24

    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.

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

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

    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.

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

    Time frame: Baseline, Week 24

    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.

  7. Percent Change From Baseline Over Time Through Week 48 in Fasting HDL-C

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

    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.

  8. Percent Change From Baseline at Week 24 in Fasting Total Apolipoprotein B (ApoB)

    Time frame: Baseline, Week 24

    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.

  9. Percent Change From Baseline Over Time Through Week 48 in Fasting Total ApoB

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

    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.

  10. Percent Change From Baseline at Week 24 in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C)

    Time frame: Baseline, Week 24

    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.

  11. Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C

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

    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.

  12. Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    Time frame: Up to Week 48

    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.

Sponsors and collaborators

Lead sponsor

Arrowhead Pharmaceuticals

Industry

Registry information

Official study title

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

Acronym: MUIR

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Aug 10, 2021
Registry last updated
Apr 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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