Plozasiran for adults with severe high triglycerides at risk of acute pancreatitis

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This randomized, double-blind phase 3 trial will enroll about 288 adults with severe hypertriglyceridemia and a recent history of acute pancreatitis to receive plozasiran 25 mg subcutaneously every three months or matching placebo. Participants will be counseled to remain on a low-fat diet and continue background lipid‑lowering medications while safety and efficacy, including adjudicated pancreatitis events and triglyceride levels, are monitored. After the double-blind period or a confirmed pancreatitis event, participants may enter a 12-month open-label extension receiving plozasiran. The trial is designed to determine whether regular plozasiran dosing provides sustained triglyceride reduction and fewer pancreatitis recurrences in this high-risk group.

Why it matters

Who can join: the full rules

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

Where it's running

• Research Site
  Los Angeles, California, United States Recruiting
• Clinical Research Site 4
  Santa Clarita, California, United States Recruiting
• Research Site
  New Haven, Connecticut, United States Recruiting
• Clinical Research Site 6
  Springfield, Illinois, United States Recruiting
• Research Site
  Indianapolis, Indiana, United States Recruiting
• Research Site
  Kansas City, Kansas, United States Recruiting

+90 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Medical Monitor
• Email: plozasiran@arrowheadpharma.com
• Phone: 626-304-3400

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• Russian registry for people with very high triglycerides

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.