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)
Study on Investigational Medication for Severe Hypertriglyceridemia (High Blood Triglycerides)
Mark Gromski, MD
Primary Investigator
Brief description of study
This study will evaluate the efficacy and safety of plozasiran in approximately 140 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.
Detailed description of study
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.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Severe Hypertriglyceridemia
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Age: 18 years - 100 years
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Gender: All
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 2 prior AP events not attributed to other etiologies with at least 1 occurring within the last 12 months prior to Screening.
- Fasting low-density lipoprotein cholesterol (LDL-C) ≤ 130 mg/dL (≤ 3.37 mmol/L) at Screening
- Screening hemoglobin A1c (HbA1c) ≤ 9.0%
- 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:
- 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
This study investigates severe hypertriglyceridemia (SHTG), a condition where there are high levels of fats called triglycerides in the blood. The purpose of this study is to evaluate the effects of an investigational medication in adults who have had at least two episodes of acute pancreatitis, a sudden inflammation of the pancreas, with one occurring in the last year.
Participants in this study will receive either the investigational medication or a placebo, which is an inactive substance that looks like the investigational medicine but does not contain any medicine, through an injection every three months. They will also follow a low-fat diet and continue their current medications. After the initial treatment period, all participants will have the option to receive the investigational medication for an additional 12 months.
- Who can participate: Adults with severe hypertriglyceridemia who have had at least two acute pancreatitis events, with one in the past year, may join. Participants must have specific triglyceride and cholesterol levels and be willing to follow a low-fat diet.
- Study details: Participants will receive an injection every three months and follow a low-fat diet. They will continue their usual medications.
