Mixed DyslipidemiaPhase 2MUIRNCT04998201
Study of Plozasiran (ARO-APOC3) in Adults With Mixed Dyslipidemia
A Phase 2 study testing ARO-APOC3 in people with Mixed Dyslipidemia, run by Arrowhead Pharmaceuticals at 30 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mixed Dyslipidemia
- What is being tested?
- ARO-APOC3
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 353 participants
- Where
- 30 sitesin 6 countries
- Study dates
- 28 Sep 2021to 14 Aug 2023
- Phase
- Phase 2
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
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
30 sites in 6 countries.
30 sites in 6 countries
United States15 sites
Research Site 3
Beverly Hills, California, 90211
Research Site 2
Boca Raton, Florida, 33434
Research Site 12
Dayton, Ohio, 45419
Research Site 18
Dunwoody, Georgia, 30338
Research Site 1
Fort Lauderdale, Florida, 33308
Research Site 4
Franklin, Ohio, 45005
Research Site 7
Greenville, South Carolina, 29607
Research Site 6
Houston, Texas, 77002
Research Site 32
Houston, Texas, 77030
Research Site 31
Las Vegas, Nevada, 89121
Research Site 14
Miami Springs, Florida, 33166
Research Site 17
New Windsor, New York, 12553
Research Site 8
Northridge, California, 91325
Research Site 5
Pembroke Pines, Florida, 33024
Research Site 13
San Antonio, Texas, 78249
Australia4 sites
Research Site 29
Adelaide, South Australia, 5000
Research Site 19
Clayton, Victoria, 3168
Research Site 27
Joondalup, Western Australia, 6027
Research Site 30
Morayfield, Queensland, 4506
Poland4 sites
Research Site 28
Lodz, 93-338
Research Site 24
Lodz, 94-048
Research Site 25
Poznan, 61-655
Research Site 26
Rzeszów, 35-055
Hungary3 sites
Research Site 20
Balatonfüred, H-8230
Research Site 21
Debrecen, H-4032
Research Site 22
Nyíregyháza, H-4405
Canada2 sites
Research Site 15
Concord, Ontario, L4K 4M2
Research Site 10
Montreal, Quebec, H2W2T2
New Zealand2 sites
Research Site 11
Auckland, 2025
Research Site 16
Christchurch, 8013
About this study
Official title: 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.
- Conditions
- Mixed Dyslipidemia
- Being tested
- ARO-APOC3, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARO-APOC3Drug
Also called Plozasiran
ARO-APOC3 Injection
PlaceboDrug
Sterile Normal Saline (0.9% NaCl)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: ARO-APOC3 |
| Placebo | Placebo comparator | Volume-matched placebo SC injection on Day 1 and Week 12 for a total of 2 injections Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Week 24
Secondary outcomes (12)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2021
- Study start28 Sep 2021
- Primary completion10 Feb 2023
- Study completion14 Aug 2023
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 (1)Papers the sponsor has linked to this study.
- Other trials for Mixed DyslipidemiaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 353 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
- NCT04998201
- Sponsor's protocol ID
- AROAPOC3-2002
- Other IDs
- 2021-000688-57
- Acronym
- MUIR
- Status last verified
- Apr 2026
- First submitted
- 3 Aug 2021
- Last updated
- 14 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 38804517