Study of Plozasiran in Adults With Severe Hypertriglyceridemia at Risk of Acute Pancreatitis
Purpose
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.
Condition
- Severe Hypertriglyceridemia
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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) |
|
Recruiting Locations
Research Site
Los Angeles 5368361, California 5332921 90027
Los Angeles 5368361, California 5332921 90027
Clinical Research Site 4
Santa Clarita 5393049, California 5332921 91321
Santa Clarita 5393049, California 5332921 91321
Clinical Research Site 6
Springfield 4250542, Illinois 4896861 62702
Springfield 4250542, Illinois 4896861 62702
Research Site
Indianapolis 4259418, Indiana 4921868 46202
Indianapolis 4259418, Indiana 4921868 46202
Research Site
Kansas City 4273837, Kansas 4273857 66160
Kansas City 4273837, Kansas 4273857 66160
Research Site
St Louis 4407066, Missouri 4398678 63110
St Louis 4407066, Missouri 4398678 63110
Clinical Research Site 5
North Platte 5697939, Nebraska 5073708 69101
North Platte 5697939, Nebraska 5073708 69101
Clinical Research Site 3
Greensboro 4469146, North Carolina 4482348 27401
Greensboro 4469146, North Carolina 4482348 27401
Research Site
Wilmington 4499379, North Carolina 4482348 28412
Wilmington 4499379, North Carolina 4482348 28412
Clinical Research Site 7
Philadelphia 4560349, Pennsylvania 6254927 19107
Philadelphia 4560349, Pennsylvania 6254927 19107
Clinical Research Site 1
Mesquite 4710826, Texas 4736286 75149
Mesquite 4710826, Texas 4736286 75149
Clinical Research Site 2
San Antonio 4726206, Texas 4736286 78233
San Antonio 4726206, Texas 4736286 78233
More Details
- Status
- Recruiting
- Sponsor
- Arrowhead Pharmaceuticals