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

Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Plozasiran in Adults With Severe Hypertriglyceridemia at High Risk of Acute Pancreatitis (SHASTA-5 Study)

Phase 3 Interventional Arrowhead Pharmaceuticals · NCT06880770

This trial will test whether plozasiran injections every three months can lower triglycerides and reduce pancreatitis risk in adults with severe high triglycerides who have had multiple recent pancreatitis attacks.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment288 (estimated)
Ages18 Years and up
SexAll
SponsorArrowhead Pharmaceuticals Industry-sponsored
Locations83 sites (Los Angeles, California and 82 other locations)
Trial IDNCT06880770 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Ideal candidates are adults with severe hypertriglyceridemia (fasting triglycerides ≥880 mg/dL) with recent recurrent acute pancreatitis who can follow a low-fat diet and remain on standard lipid‑lowering therapies.

Not a fit: Patients without severe triglyceride elevations, those whose pancreatitis is primarily due to other causes, pregnant or breastfeeding people, or those recently treated with other hepatocyte-targeted siRNA therapies are unlikely to benefit from this study.

Why it matters

Potential benefit: If effective, plozasiran could lower triglyceride levels and reduce the frequency or severity of acute pancreatitis attacks in people with severe hypertriglyceridemia.

How similar studies have performed: Other triglyceride-lowering therapies have reduced triglyceride levels and in some cases lowered pancreatitis risk, but plozasiran is a newer agent and robust phase 3 evidence is still limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
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 this trial is running

Los Angeles, California and 82 other locations

+33 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Severe Hypertriglyceridemia
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.