Purpose:
Severe hypertriglyceridemia (SHTG) is a disorder characterized by marked elevations in triglyceride levels in your blood, which can lead to acute and potentially life-threatening pancreatitis. The American Heart Association and American College of Cardiology recommend triglyceride-lowering therapy when levels are ≥500 mg/dL to prevent acute pancreatitis. Conventional management of SHTG includes dietary restrictions of fat and alcohol, lipid-lowering medications, and lifestyle changes, including exercise and caloric restriction.
Apolipoprotein C3 is an important regulator of triglyceride metabolism and triglyceride levels by inhibiting enzymes responsible for triglyceride lowering, such as lipoprotein lipase. Patients with SHTG typically have increased APOC3 levels that lead to elevated triglyceride levels in the blood. Plozasiran is a synthetic small interfering ribonucleic acid [siRNA]) designed to specifically silence the mRNA that codes for the APOC3 protein and block its production in the liver cells. It has been shown to reduce circulating triglyceride levels to normal in an effective and safe manner. The purpose of this study is to demonstrate the ability of plozasiran to reduce fasting serum TG levels and to also evaluate the efficacy of plozasiran in reducing the incidence of abdominal pain related to acute pancreatitis and emergency room visits or hospitalizations for abdominal pain attributed to hypertriglyceridemia and events of documented pancreatitis. Pancreatitis is a potentially fatal complication of SHTG.
Description:
This is a multicenter, randomized, placebo-controlled Phase 3 study to evaluate the efficacy and safety of plozasiran injection in adult subjects with SHTG. Subjects who have met all the protocol eligibility criteria during screening will be randomly assigned in a 2:1 ratio in a double-blind fashion to receive easy-to-administer subcutaneous injections of either plozasiran (2/3rds of subjects) or matching placebo (1/3rd of subjects). The double-blind treatment period duration will be up to 1 year, with four doses taken every three months. After Month 12, eligible subjects will be offered an opportunity to continue in an optional open-label extension (OLE) study that will last up to 2 years, during which all patients will receive plozasiran with no change.
Key Eligibility Requirements:
(Please note: Additional eligibility requirements may be assessed at the time of study screening evaluation.)
- Males or nonpregnant (who do not plan to become pregnant) nonlactating females who are ≥18 years of age at screening
- Established diagnosis of SHTG and prior documented fasting triglyceride levels of ≥500 mg/dL
- Fasting LDL-C ≤130 mg/dl
Subjects will be excluded if:
- They have uncontrolled diabetes with an HBA1C is > 8.5
- History of malignancy within the last two years.
- Chronic kidney disease, defined by an estimated glomerular filtration rate (eGFR) <20 mL/min/1.73 m2
PARTICIPATION IN THIS TRIAL CAN BE UP TO THREE YEARS
The information we are providing includes important background on a variety of important cardiovascular conditions and ongoing clinical trials. We encourage you to use this information in discussions with your health care professional. Since enrollment in clinical trials are limited in time, we can’t guarantee their availability at any given time. However, we have continued access to new clinical trial opportunities and will share them as soon as they are available.