Recruiting
Phase 3

Plozasiran

Sponsor:

Arrowhead Pharmaceuticals

Code:

NCT06880770

Conditions

Severe Hypertriglyceridemia

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Plozasiran

Placebo

Study Details

Brief summary:

This study will evaluate the efficacy and safety of plozasiran in approximately 288 adult participants with severe hypertriglyceridemia (SHTG) and history of at least two prior acute pancreatitis (AP) events not attributed to other etiologies, with at least one occurring within the last 12 months prior to screening. Eligible participants will be randomly assigned in a double-blind manner to either receive plozasiran 25 mg by subcutaneous (SC) injection every three months (Q3M) or matching placebo. Enrolled participants will be counseled to remain on the specified low-fat diet and background medications throughout the study. Following completion of the double-blind treatment period, or if the participant has a positively adjudicated AP event (whichever occurs first), participants will transition to the 12-month Open-Label Extension (OLE) treatment period receiving plozasiran 25 mg by SC injection Q3M.

Conditions

Severe Hypertriglyceridemia

Study ID

NCT06880770

Start date

Apr 24, 2025

Status verified date

Sep, 2026

Completion date

Jun, 2029

Anticipated

Primary completion date

Mar, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Males, or nonpregnant (who do not plan to become pregnant) nonlactating females
  • Established diagnosis of SHTG and prior documented evidence of fasting TG levels of ≥ 880 mg/dL (≥ 10 mmol/L)
  • Documented evidence of at least 1 prior AP event not attributed to other etiologies occurring within the last 60 months prior to Screening.
  • Fasting low-density lipoprotein cholesterol (LDL-C) ≤ 130 mg/dL (≤ 3.37 mmol/L) at Screening
  • Screening hemoglobin A1c (HbA1c) ≤ 9.5%
  • Willing to follow diet counseling and maintain a stable low-fat diet
  • Must be on standard of care lipid and TG-lowering medications per local guidelines (unless documented as intolerant, or a treatment failure as determined by the Investigator)

Exclusion Criteria:

  • Use of any hepatocyte-targeted small interfering ribonucleic acid (siRNA) that targets lipids and/or triglycerides within 365 days before Day 1, except inclisiran.
  • Use of any other hepatocyte targeted siRNA or antisense oligonucleotide molecule within 60 days or within 5 half-lives lives before day 1. Whichever is longer.
  • AP ≤ 4 weeks prior to Randomization/Day 1
  • Body mass index (BMI) > 45 kg/m\^2
  • Any planned bariatric surgery or similar procedures to induce weight lost starting at consent through End of Study (EOS)
  • Planned coronary intervention (e.g. stent placement or heart bypass) during the study
  • History of arterial revascularization within 16 weeks of Screening
  • History of acute coronary syndrome event within 24 weeks of Screening
  • Recent atherosclerotic cardiovascular disease (ASCVD) event within 24 weeks of Screening
  • Recent unstable or symptomatic cardiac arrhythmia (including any associated medication changes) within 90 days of Screening. Individuals with stable well-controlled atrial arrhythmia will be allowed to participate in the study
  • History of pacemaker or automatic implantable cardioverter defibrillators implant within 30 days before Screening
  • New York Heart Association Class III-IV heart failure or last known ejection fraction of < 30%
  • Current diagnosis of nephrotic syndrome
  • Chronic kidney disease, defined by an estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73 m\^2
  • Liver disease defined as cirrhosis or Child-Pugh Class B and C, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5× Upper Limit of Normal (ULN) at Screening

Note: Additional Inclusion/Exclusion Criteria may apply per protocol

Study Design

Enrollment

288 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Plozasiran Injection

Plozasiran by SC injection every 3 months (Q3M) through completion of the randomized period

Plozasiran by SC injection Q3M through completion of the OLE period

experimental: Placebo

calculated volume to match active treatment by SC injection (randomized period)

Interventions

Plozasiran

ARO-APOC3 injection

Placebo

sterile normal saline (0.9% NaCl)

Primary outcome measure

  • Time to First Occurrence of Positively Adjudicated AP Event (Event Occurring More Than 10 Days After First Dose of Study Drug) [ Time Frame: Randomization up to end of Double Blind Treatment Period compared to placebo (Approximate Maximum 50 Months)] ]

Central Contacts and Locations

Central contacts

Medical Monitor

626-304-3400plozasiran@arrowheadpharma.com

Locations

Research Site

Recruiting

Los Angeles, California, United States, 90027

Clinical Research Site 4

Recruiting

Santa Clarita, California, United States, 91321

Research Site

Recruiting

New Haven, Connecticut, United States, 06519

Clinical Research Site 6

Recruiting

Springfield, Illinois, United States, 62702

Research Site

Recruiting

Indianapolis, Indiana, United States, 46202

Research Site

Recruiting

Kansas City, Kansas, United States, 66160

Research Site

Recruiting

Ann Arbor, Michigan, United States, 48109

Research Site

Recruiting

St Louis, Missouri, United States, 63110

Clinical Research Site 5

Recruiting

North Platte, Nebraska, United States, 69101

Research Site

Recruiting

New York, New York, United States, 10029

Clinical Research Site 3

Recruiting

Greensboro, North Carolina, United States, 27401

Research Site

Recruiting

Wilmington, North Carolina, United States, 28412

Clinical Research Site 7

Recruiting

Philadelphia, Pennsylvania, United States, 19107

Research Site

Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Clinical Research Site 1

Recruiting

Mesquite, Texas, United States, 75149

Clinical Research Site 2

Recruiting

San Antonio, Texas, United States, 78233

Research Site

Recruiting

Seattle, Washington, United States, 98109

Research Site

Recruiting

Montreal, Quebec, Canada, H2W 1R7

More Information

Sponsor

Arrowhead Pharmaceuticals

Last update posted

Sep 2, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Arrowhead Pharmaceuticals on 2026-09-02.